AU2006230674A8 - Methods for the Treatment of Synucleinopathies - Google Patents

Description

I

AUSTRALIA

Patents Act 1990 COMPLETE SPECIFICATION FOR A STANDARD PATENT Name of Applicant: Address for Service: Invention Title: The Brigham and Women's Hospital, Inc.

CULLEN CO.

Level 26 239 George Street Brisbane Qld 4000 Methods for the Treatment of Synucleinopathies The following statement is a full description of the invention, including the best method of performing it, known to us:

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8 FIELD OF THE INVENTION The present invention relates to therapeutic approaches to the treatment of O synucleinopathies, such as Parkinson's Disease Diffuse Lewy Body Disease (DLBD) and 00 Multiple System Atrophy (MSA).

BACKGROUND OF THE INVENTION Synucleinopathies are a diverse group of neurodegenerative disorders that share a O common pathologic lesion containing aggregates of insoluble a-synuclein protein in selectively c vulnerable populations of neurons and glia. Certain evidence links the formation of abnormal \filamentous aggregates to the onset and progression of clinical symptoms and the degeneration 0 10 of affected brain regions in neurodegenerative disorders including Parkinson's disease, diffuse Lewy body disease and multiple system atrophy. The clinical treatments of these diseases include carbidopa-levodopa, anticholinergics and symptomatic medication, although for some synucleinopathies such as diffuse Lewy body disease a specific therapy does not exist. Most Parkinson's subjects that initially respond well to levodopa develop motor fluctuations and a "wearing-off" phenomenon within five years. Given the severe debilitating nature of these disorders and their prevalence there is a clear need in the art for novel approaches towards treating and managing these diseases.

SUMMARY OF THE INVENTION The present invention relates to therapeutic approaches to the treatment of synucleinopathies, such as Parkinson's Disease Diffuse Lewy Body Disease (DLBD) and Multiple System Atrophy (MSA) by treatment with farnesyl transferase inhibitor compounds.

In one aspect, the invention provides methods for treating a synucleinopathic subject by administering a composition comprising a farnesyl transferase inhibitor compound in a therapeutically effective amount. In some embodiments, the composition includes one or more farnesyl transferase inhibitor compounds and their analogs disclosed herein and incorporated by reference, or one or more stereoisomeric forms or pharmaceutically acceptable acid or base addition salt forms thereof. In one embodiment, the composition includes one or more of farnesyl transferase inhibitor compound of Figure 5, or a stereoisomeric form or a pharmaceutically acceptable acid or base addition salt form thereof.

In another aspect, the invention provides methods for treating a synucleinopathic subject by administering both a farnesyl transferase inhibitor compound and a second therapeutic compound in therapeutically effective amounts. The two compounds can be administered as a combination composition comprising both compounds. Alternatively, the two compounds can be administered separately as two different compositions) either simultaneously or

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sequentially as described herein. In some embodiments, the faresyl transferase inhibitor S composition includes one or more famesyl transferase inhibitor compounds disclosed herein, or O one or more stereoisomeric forms or pharmaceutically acceptable acid or base addition salt 0o forms thereof. In one embodiment, a farnesyl transferase inhibitor composition includes one or more farnesyl transferase inhibitor compounds of Figure 5, or a stereoisomeric form or a pharmaceutically acceptable acid or base addition salt form thereof. In some embodiments, the \second therapeutic compound includes, but is not limited to dopamine agonists such as Pramipexole, and Memantine, Aricept, and other acetycholinesterase inhibitors.

IsO According to the invention, FTI-277 lowers synuclein level in COS-7 cells and inhibits 0 10 synuclein toxicity in SH-SY5Y cells. These cells are dopaminergic neuroblastoma cells and can be useful for analyzing Parkinson's Disease pathogenesis.

It should be appreciated that aspects and embodiments of the invention described herein in connection with one farnesyl transferase inhibitor also may be practiced using two or more farnesyl transferase inhibitors between 2 and 50, between 2 and 25, between 2 and 10, 2, 3, 4, 5, 6, 7, 8, or Similarly, aspects and embodiments of the invention described herein in connection with one other compound also may be practiced using two or more other compounds between 2 and 50, between 2 and 25, between 2 and 10, 2, 3, 4, 5, 6, 7, 8, or 9).

BRIEF DESCRIPTION OF THE DRAWINGS Figure 1 shows that UCH-L1 membrane association is regulated by its farnesylation.

Figure 2 shows that C220S mutation abolished the inhibitory effect of UCH-LI WT on a-synuclein degradation.

Figure 3 shows that farnesyl transferase inhibitor can rescue the a-synuclein toxicity in infected SH-SY5Y cells.

Figure 4 shows that FTI-277 rescued a-synuclein toxicity in SH-SY5Y cells by reducing the amount of a-synuclein accumulation.

Figure 5 shows the formula of compound Rl 15777, BMS 214662, SCH 66336, SCH 44342 and L778,123.

Figure 6 shows structures of farnesyl transferase inhibitor compounds.

Figure 7 shows structures of farnesyl transferase inhibitor compounds.

Figure 8 shows structures of farnesyl transferase inhibitor compounds.

Figure 9 shows structures of farnesyl transferase inhibitor compounds.

Figure 10 shows structures of farnesyl transferase inhibitor compounds.

Figure 11 shows structures of farnesyl transferase inhibitor compounds.

Figure 12 shows structures of farnesyl transferase inhibitor compounds.

Figure 13 shows structures of farnesyl transferase inhibitor compounds.

Figure 13 shows structures of famesyl transferase inhibitor compounds.

Figure 14 shows structures of farnesyl transferase inhibitor compounds.

00 Figure 15 shows structures of famesyl transferase inhibitor compounds.

Figure 16 shows structures of famesyl transferase inhibitor compounds.

Figure 17 shows structures of famesyl transferase inhibitor compounds.

O Figure 18 shows structures of famesyl transferase inhibitor compounds.

^Q Figure 19 shows structures of famesyl transferase inhibitor compounds.

Figure 20 shows structures of farnesyl transferase inhibitor compounds.

0 0 10 Figure 21 shows farnesyl transferase inhibitor compounds.

Figure 22 shows farnesyl transferase inhibitor compounds.

DETAILED DESCRIPTION The invention provides methods, compositions and articles of manufacture for treating synucleinopathic subjects. Methods of the invention are useful to accelerate the degradation of a-synuclein, the accumulation of which is pathogenic in synucleinopathies. The invention provides methods for treating a synucleinopathic subject, including the step of administering to the synucleinopathic subject a therapeutically effective amount of a faresyl transferase inhibitor compound or a therapeutical preparation, composition, or formulation of the compound such as those described herein, including those in the Claims, Figures, and patents and publications listed herein. In preferred embodiments, the synucleinopathic subject is a human.

In one embodiment, the invention is a method for treating a synucleinopathic subject comprising administering to the synucleinopathic subject a farnesyl transferase inhibitor of the formula: or a stereoisomeric form or a pharmaceutically acceptable acid or base addition salt form thereof, at a therapeutically effective dose and frequency.

In another embodiment, the invention is a method for treating a synucleinopathic subject comprising administering to the synucleinopathic subject a famesyl transferase inhibitor of the formula: wherein the dotted line represents an optional bond; X is oxygen or sulfur; R' is hydrogen, C-I-1 2 alkyl, Ar 1 Ar 2 Ci- 6 alkyl, quinolinylCl_ 6 alkyl, pyridylCi-6 alkyl, hydroxyCl-6 alkyl, C 1 6 alkyloxyC 1 6 alkyl, mono- or di(Ci-6 alkyl)aminoCi.

6 alkyl, aminoC 1 6 alkyl, or a radical of formula -Alk' 9 -Alk' -S(O)-R 9 or -Alk' -S(0) 2

-R

9 wherein Alk' is Ci.

6 alkanediyl,

R

9 is hydroxy, C 1 6 alkyl, C 1 6 alkyloxy, amino, C 1 -8 alkylamino or C 1 8 alkylamino substituted with C1- 6 alkyloxycarbonyl; 02 3 16 o) R R and R each independently are hydrogen, hydroxy, halo, cyano, C 1 6 alkyl, C 1 6 00 alkyloxy, hydroxyCl.

6 alkyloxy, C 1 6 alkyloxyC,.6 alkyloxy, aminoCI- 6 alkyloxy, mono- or di(C 1.

6 alkyl)aminoC 1 6 alkyloxy, Ar 1 Ar 2 C1-6 alkyl, Ar 2 oxy, Ar 2

C

1 6 alkyloxy, hydroxycarbonyl, C 1 6 alkyloxycarbonyl, trihalomethyl, trihalomethoxy, C 2 6 alkenyl, 4,4dimethyloxazolyl; 2 3 or when on adjacent positions R and R 3 taken together may form a bivalent radical of formula -OCH C O-O-CH 2 -CH 0- -0-CH=CH- -0-CH 2

-CH

2 -0-CR 2

-CR

2

-CH

2 or -CH=CH-CH=CH- R 4 and R 5 each independently are hydrogen, halo, Ar 1 C1_ 6 alkyl, hydroxyCl- 6 alkyl, C 1 6 alkyloxyCl- 6 alkyl, C 1 6 alkyloxy, C 1 6 aikylthio, amino, hydroxycarbonyl, C,.

6 alkyloxycarbonyl, C1- 6 alkylS(0)CI- 6 alkyl or C1- 6 alkylS(0) 2

C

1 6 alkyl; R 6 and R' each independently are hydrogen, halo, cyano, C 1 6 alkyl, C1- 6 alkyloxy, Ar 2 oxy, trihalomethyl, C1- 6 alkylthio, di(C 1 6 aikyl)amino, or when on adjacent positions R 6 and R 7 taken together may formn a bivalent radical of formula -0-CR 2 or -CH=CH-CH=CH- R 8 is hydrogen, C 1 6 alkyl, cyano, hydroxycarbonyl, C 1 6 alkyloxycarbonyl, C 1 6 alkylcarbonylC 1 6 alkyl, cyanoC 1 6 alkyl, C 1 6 alkyloxycarbonylC 1 6 alkyl, carboxyC 16 alkyl, hydroxyC 1 6 alkyl, aminoC 1- 6 alkyl, mono- or di(C 1- 6 alkyl)aminoC 1 6 alkyl, imidazolyl, haloC 1 6 alkyl, C 1 6 alkyloxyCl- 6 alkyl, aminocarbonylC 1 6 alkyl, or a radical of formula -0-R1 0 1), 2),

-N-R'

1 I R'1 2 3), wherein

R'

0 is hydrogen, CQ.

6 alkyl, CQ- 6 alkylcarbonyl, Ar', Ar 2

C,.

6 alkyl, C 1 6 alkyloxycarbonylC 1 6 alkyl, a radical or formula -Alk 2 -OR'1 3 or -Alk 2

-NR"

4

R'

R 1 1 is hydrogen, C 1- 12 alkyl, Ar' or Ar 2 C 1 6 alkyl; S R 1 2 is hydrogen, Ci-6 alkyl, Ci-1 6 alkylcarbonyl, Cl-6alkyloxycarbonyl, CI.

6 S alkylaminocarbonyl, Ar', Ar 2 C1- 6 alkyl, C1.

6 alkylcarbonylCi.

6 alkyl, a natural amino acid, Ar' O carbonyl, Ar 2

CI-

6 alkylcarbonyl, aminocarbonylcarbonyl, CI.

6 alkyloxyCi.

6 alkylcarbonyl, 00 hydroxy, CI.

6 alkyloxy, aminocarbonyl, di(Ci-6 alkyl)aminoC,.

6 alkylcarbonyl, amino, C1-6 alkylamino, CI.

6 alkylcarbonylamino, or a radical of formula -Alk 2

-OR

1 3 or -Alk 2

-NR

1 4

R

5 wherein 0 Alk 2 is C.- 6 alkanediyl; 3 R 1 is hydrogen, CI- 6 alkyl, Ci.

6 alkylcarbonyl, hydroxyC.-6 alkyl, Ar' or Ar 2 C16 alkyl;

R

14 is hydrogen, CI- 6 alkyl, Ar' or Ar 2

CI-

6 alkyl;

R

5 is hydrogen, CI- 6 alkyl, Ci-6 alkylcarbonyl, Ar' or Ar 2 Ci-6 alkyl;

R

1 7 is hydrogen, halo, cyano, CI- 6 alkyl, C1- 6 alkyloxycarbonyl, Ar

R

18 is hydrogen, Ci.

6 alkyl, C1- 6 alkyloxy or halo;

R

1 9 is hydrogen or C1- 6 alkyl; Ar' is phenyl or phenyl substituted with Ci-6 alkyl, hydroxy, amino, Ci- 6 alkyloxy or halo; and Ar 2 is phenyl or phenyl substituted with Ci- 6 alkyl, hydroxy, amino, Ci-6 alkyloxy or halo; or a stereoisomeric form or a pharmaceutically acceptable acid or base addition salt form thereof, at a therapeutically effective dose and frequency.

In another embodiment, the invention is a method for treating a synucleinopathic subject comprising administering to the synucleinopathic subject a farnesyl transferase inhibitor of the formula:

R

3

R

16 R

N

R 2 R4 HNR2

HN

R

8 R17 R1 8

R

N R19

R

6 wherein R 2

R

3 and R 1 6 each independently are hydrogen, hydroxy, halo, cyano, Ci-6 alkyl, CI- 6 alkyloxy, hydroxyCi.

6 alkyloxy, Ci.

6 alkyloxyCl-6 alkyloxy, aminoCi.

6 alkyloxy, mono- or di(CI- 6 alkyl)aminoCi.

6 alkyloxy, Ar 1 Ar 2 C alkyl, Ar 2 oxy, Ar 2 C 1 6 alkyloxy, N_ hydroxycarbonyl, C 1 6 alkyloxycarbonyl, trihalomethyl, trihalomethoxy, C 2 6 alkenyl, 4,4o dimethyloxazolyl; or 00 when on adjacent positions R 2 and R 3 taken together may form a bivalent radical of formula

-O-CH

2 (a-i1),

-O-CH

2

-CH

2 -O-CH=CH-

ID-O-CH

2

-CH

2

-O-CH

2

-CH

2

-CH

2 or -CH=CH-CH=CH-

R

4 and R 5 each independently are hydrogen, halo, Ar', C 1 6 alkyl, hydroxyCI- 6 alkyl, CI_ 6 alkyloxyC 16 alkyl, C 1 6 alkyloxy, C 1 6 alkylthio, amino, hydroxycarbonyl, C 1- 6 alkyloxycarbonyl, C 1 6 alkylS(0)C 1 6 alkyl or CI.

6 alkylS(O) 2

C

1 6 alkyl; R 6 and R 7 each independently are hydrogen, halo, cyano, C 1 6 alkyl, C 1 6 alkyloxy, Ar 2 oxy, trihalomethyl, C 1 6 alkylthio, di (CI- 6 alkyl) amino, or when on adjacent positions R 6 and R 7 taken together may form a bivalent radical of formula

-O-CH

2 or

R.

8 is hydrogen, C,.

6 alkyl, cyano, hydroxycarbonyl, C,.

6 alkyloxycarbonyl, C 1 .6 alkylcarbonylC 1 6 alkyl, cyanoC,.

6 alkyl, CI.

6 alkyloxycarbonylC,.

6 alkyl, carboxyCI- 6 alkyl, hydroxyC,.

6 alkyl, aminoC,.

6 alkyl, mono- or di(C,.

6 alkyl)aminoC,.

6 alkyl, imidazolyl, haloC 1 6 alkyl, C,1- 6 alkyloxyC 1 6 alkyl, aminocarbonylC 1.

6 alkyl, or a radical of formula -0-R1 0 1), 2), R 2 3), wherein

R'

0 is hydrogen, C 1 6 alkyl, C 1 6 alkylcarbonyl, Ar', Ar 2

C

1 6 alkyl, C 1 6 alkyloxycarbonylC.

6 alkyl, a radical or formula -Alk 2 -OR'1 3 or -Alk 2

-NR'

4

R"

R" is hydrogen, C,-1 2 alkyl, Arl or Ar 2

C,.

6 alkyl; R 12is hydrogen, CI.

6 alkyl, C,.

6 alkylcarbonyl, C 1 6 alkyloxycarbonyl, C,.

6 alkylaminocarbonyl, 1 2 2 Ar Ar C,.

6 alkyl, C,.

6 alkylcarbonylC,.

6 alkyl, a natural amino acid, Arl carbonyl, Ar C,.

6 alkylcarbonyl, aminocarbonylcarbonyl, C,.

6 alkyloxyCI.

6 alkylcarbonyl, hydroxy, C,.

6 alkyloxy, aminocarbonyl, di(Cl.-6 alkyl) aminoCI 6 alkylcarbonyl, amino, C.1-6 alkylamino, C,.

6 S alkylcarbonylamino, or a radical of formula -Alk 2

-OR'

3 or -Alk 2

-NR'

4

R

5 02 O wherein Alk 2 is C1- 6 alkanediyl; 00 R' 3 is hydrogen, C1.

6 alkyl, C1- 6 alkylcarbonyl, hydroxyCl- 6 alkyl, Ar' or Ar 2

C,-

6 alkyl; R1 4 is hydrogen, C,.

6 alkyl, Ar' or Ar 2 C1- 6 alkyl;

R'

5 is hydrogen, C.-6 alkyl, C1- 6 alkylcarbonyl, Ar' or Ar 2 C1 6 alkyl; R is hydrogen, halo, cyano, C,-6 alkyl, C,- 6 alkyloxycarbonyl, Ar'; 18 R is hydrogen, C,.

6 alkyl, C, 6 alkyloxy or halo; IN R19 is hydrogen or C,- 6 alkyl; 0 10 a stereoisomeric form or a pharmaceutically acceptable acid or base addition salt form thereof, at a therapeutically effective dose and frequency.

In another embodiment the invention is a method for treating a synucleinopathic subject comprising administering to the synucleinopathic subject a farnesyl transferase inhibitor with the formula: R3 R16 2 R R R wherein R2, R and R' 6 each independently are hydrogen, hydroxy, halo, cyano, C,.

6 alkyl, C,.

6 alkyloxy, hydroxyC,.

6 alkyloxy, C,.

6 alkyloxyC,.

6 alkyloxy, aminoCl.

6 alkyloxy, 2 2 mono- or di(C,.

6 alkyl)aminoC,- 6 alkyloxy, Ar 1 Ar 2

C,.

6 alkyl, Ar2 oxy, Ar2 C,.

6 alkyloxy, hydroxycarbonyl, C,.

6 alkyloxycarbonyl, trihalomethyl, trihalomethoxy, C 2 6 alkenyl, 4,4dimethyloxazolyl; or when on adjacent positions R 2 and R 3 taken together may form a bivalent radical of formula H N R8 17, 1 8 77 R19

R

wherein R 2 R 3 and R 16 each independently are hydrogen, hydroxy, halo, cyano, C1.6 alkyl, C1-6 alkyloxy, hydroxyCl-6 alkyloxy, C1-6 alkyloxyCl-6 alkyloxy, aminoCI-6 alkyloxy, mono- or di(CI-6 alkyl)aminoCI-6 alkyloxy, Ar Ar2 C1-6 alkyl, ArZ oxy, ArZ C1-6 alkyloxy, hydroxycarbonyl, C1-6 alkyloxycarbonyl, trihalomethyl, trihalomethoxy, C-6 alkenyl, 4,4dimethyloxazolyl; or when on adjacent positions R 2 and R 3 taken together may form a bivalent radical of formula (a-I)

-O-CH

2 -0- -0-CH 2

-CH

2 o-O-CH=CH- 00 -O-CH 2

-CH

2 -0-CH 2

-CH

2

-CH

2 or -CH=CH-CH=CH- R 4 and R 5 each independently are hydrogen, halo, Ar', C, 4 6 alkyl, hydroxyC1- 6 alkyl, C 1 6 alkyloxyC 1- 6 alkyl, C 1- 6 alkyloxy, C,1- 6 alkylthio, amino, hydroxycarbonyl, C 1.

6 IND alkyloxycarbonyl, C,.

6 alkylS(O)C,.

6 alkyl or C,.

6 alkylS(O) 2

C

1 6 alkyl; R and R each independently are hydrogen, halo, cyano, C,- 6 alkyl, CI- 6 alkyloxy, Ar oxy, trihalomethyl, C,- 6 alkylthio, di (C 1 6 alkyl) amino, or when on adjacent positions R 6 and R 7 taken together may form a bivalent radical of formula

-O-CH

2 or -CH=CH-CH=CH- R 8 is hydrogen, C 1 6 alkyl, cyano, hydroxycarbonyl, C 1 6 alkyloxycarbonyl, C,.

6 alkylcarbonylC,.

6 alkyl, cyanoC,.

6 alkyl, C,.

6 alkyloxycarbonylC 1 6 alkyl, carboxyC 1 6 alkyl, hydroxyC,.

6 alkyl, aminoC,.

6 alkyl, mono- or di (C 1 6 alkyl)aminoC,.

6 alkyl, imidazolyl, haloC,.

6 alkyl, C,1.

6 alkyloxyC 1- 6 alkyl, aminocarbonylC 1- 6 alkyl, or a radical of formula -0-R 10 1), 2), R'1 2 3), wherein R1 0 is hydrogen, C 1 6 alkyl, C 1 6 alkylcarbonyl, Ar', Ar 2

C,.

6 alkyl, C,.

6 alkyloxycarbonylC,.

6 alkyl, a radical or formula -Alk 2 or -Alk 2 -NR'1 4 R1 5 R" is hydrogen, C 1 2 alkyl, Ar' or Ar 2

C,.

6 alkyl; R 12is hydrogen, CI6alkyl, 6 alkylcarbonyl, C,.

6 alkyloxycarbonyl, C,.

6 alkylaminocarbonyl, Ar', Ar 2

C,

4 6 alkyl, C,.

6 alkylcarbonylC,.

6 alkyl, a natural amino acid, Ar' carbonyl, Ar 2

C,.

6 alkylcarbonyl, aminocarbonylcarbonyl, C,.

6 alkyloxyCI.

6 alkylcarbonyl, hydroxy, C,.

6 alkyloxy, aminocarbonyl, di(CI- 6 alkyl)aminoCI- 6 alkylcarbonyl, amino, C,.

6 alkylamino, C,1.

6 alkylcarbonylamino, or a radical of formula -Alk 2 -OR'1 3 or -Alk 2 -NR 1 4 R'1 wherein Alk 2 is C,.

6 alkanediyl; R 1 3 is hydrogen, C,.

6 alkyl, C,.

6 alkylcarbonyl, hydroxyCI- 6 alkyl, Ar 1 or Ar 2

C,.

6 alkyl; O'4

SR

1 4 is hydrogen, C1- 6 alkyl, Ar' or Ar 2

CI-

6 alkyl; S R' 5 is hydrogen, C1- 6 alkyl, CI-6 alkylcarbonyl, Ar' or Ar 2 Ci-6 alkyl;

SR'

7 is hydrogen, halo, cyano, C1- 6 alkyl, CI- 6 alkyloxycarbonyl, Ar' 00 R 1 8 is hydrogen, C1.

6 alkyl, CI- 6 alkyloxy or halo;

R'

9 is hydrogen or C.-6 alkyl; or a stereoisomeric form or a pharmaceutically acceptable acid or base addition salt form thereof, at a therapeutically effective dose and frequency.

In another embodiment, the invention is a method for treating a synucleinopathic subject \D comprising administering to the synucleinopathic subject a faresyl transferase inhibitor of the 0 10 formula:

R

3

R

16 R2\ R NR 4

HN

8R' R18 R7 X N Ri9 R 6

R

1

R

a stereoisomeric form thereof, a pharmaceutically acceptable acid or base addition salt thereof, wherein the dotted line represents an optional bond; X is oxygen or sulfur; R' is hydrogen, Cl-12 alkyl, Ar 1 Ar 2 Ci- 6 alkyl, quinolinylCi.

6 -alkyl, pyridylCi.

6 alkyl, hydroxyCi.

6 alkyl, Ci- 6 alkyloxyCi.

6 alkyl, mono- or di(Ci.

6 alkyl)aminoCi.

6 alkyl, aminoCi-6 alkyl, or a radical of formula -Alk' 9 -Alk' -S(O)-R 9 or -Alk'-S(0) 2

R

9 wherein Alk' is C1- 6 alkanediyl,

R

9 is hydroxy, C1-6 alkyl, C1- 6 alkyloxy, amino, C.g8 alkylamino or C,.

8 alkylamino substituted with CI-6 alkyloxycarbonyl;

R

2

R

3 and R 16 each independently are hydrogen, hydroxy, halo, cyano, CI- 6 alkyl, CI-6 alkyloxy, hydroxyCI- 6 alkyloxy, C 1 6 alkyloxyCI- 6 alkyloxy, aminoC 1 6 alkyloxy, mono- or di(CI- alkyl)aminoCI.

6 alkyloxy, Ar', Ar 2

C

1 6 alkyl, Ar 2 oxy, Ar 2

CI-

6 alkyloxy, o hydroxycarbonyl, C 1 6 alkyloxycarbonyl, trihalomethyl, trihalomethoxy, C 2 6 alkenyl, 4,4- 00 dimethyloxazolyl; or when on adjacent positions R 2and R 3 taken together may form a bivalent radical of formula

-O-CH

2

I),

-O-CH

2

-CH

2 -O-CH=CH-

ID-O-CH

2

-CH

2

-O-CH

2

-CH

2

-CH

2 or -CH=CH-CH=CH- R 4 is hydrogen or C 1 6 alkyl; R 5 is hydrogen; R 6 and R 7 each independently are hydrogen, halo, cyano, C 1 6 alkyl, C 1 6 alkyloxy, Ar 2 oxy, trihalomethyl, C 1 6 alkylthio, di(C,.

6 alkyl)amino, or when on adjacent positions R 6 and R 7 taken together may form a bivalent radical of formula:

-O-CH

2 or -CH=CH-CH=CH- R 8 is hydrogen, C 1 6 alkyl, cyano, hydroxycarbonyl, C 1 .6 alkyloxycarbonyl, C 1 6 alkylcarbonylCI.

6 alkyl, cyanoCI.

6 alkyl, C 1 6 alkyloxycarbonylC 1 6 alkyl, carboxyC..

6 alkyl, hydroxyC 1 6 alkyl, aminoC 1 6 alkyl, mono- or di(C 1 6 alkyl)aminoC 1- 6 alkyl, imidazolyl, haloC 1 6 alkyl, C 1 6 alkyloxyCI.

6 alkyl, aminocarbonylC 1 6 alkyl, or a radical of formula: -O-R10(b-1), 0 -N-R IIR 12(b-3), wherein R1 0 is hydrogen, C 1 6 alkyl, C,.

6 alkylcarbonyl, Ar 1 Ar 2

C

1 6 alkyl, CI- 6 alkyloxycarbonylC 1 6 alkyl, a radical or formula Alk 2 OR'" or Alk 2 NR 1 4

R'

5 R"1 is hydrogen, C I.- 12 alkyl, Ar' or Ar 2

C

1 6 alkyl; R 1 2 is hydrogen, C 1 6 alkyl, C 1 6 alkylcarbonyl, C 1 6 alkyloxycarbonyl, C 1 6 alkylaminocarbonyl, Ar', Ar 2

CI.

6 alkyl, C 1 6 alkylcarbonylC,.

6 alkyl, a natural amino acid, Ar' carbonyl, Ar 2C 1 6 alkylcarbonyl, aminocarbonylcarbonyl, C 1 6 alkyloxyCl- 6 alkylcarbonyl, hydroxy, C,.

6 alkyloxy, aminocarbonyl, di(C,.

6 alkyl) aminoC,.

6 alkylcarbonyl, amino, C 1 6 alkylamino, CI.

6 alkylcarbonylamino, or a radical of formula -Alk 2 or -Alk 2 -NR 1 4

R'

5

ID

wherein Alk 2 is CI- 6 alkanediyl;

R

1 3 is hydrogen, CI- 6 alkyl, CI- 6 alkylcarbonyl, hydroxyCi.

6 alkyl, Arl or Ar 2 CI-6 alkyl; o R 1 4 is hydrogen, CI- 6 alkyl, Ar' or Ar 2

CI-

6 alkyl; 00 R 1 5 is hydrogen, C1- 6 alkyl, CI-6 alkylcarbonyl, Ar' or Ar 2 Cl-6 alkyl;

R

7 is hydrogen, halo, cyano, Ci.

6 alkyl, Ci- 6 alkyloxycarbonyl, Ar

R'

8 is hydrogen, C 1 -6 alkyl, C1- 6 alkyloxy or halo;

\R

1 9 is hydrogen or CI- 6 alkyl; Ar 1 is phenyl or phenyl substituted with CI- 6 alkyl, hydroxy, amino, C 1 6 alkyloxy or IN halo; and Ar 2 is phenyl or phenyl substituted with Ci- 6 alkyl, hydroxy, amino, C1- 6 alkyloxy or halo; or a stereoisomeric form or a pharmaceutically acceptable acid or base addition salt form thereof, at a therapeutically effective dose and frequency.

In another embodiment, the invention is a method for treating a synucleinopathic subject comprising administering to the synucleinopathic subject a farnesyl transferase inhibitor compound that is an enantiomer of 6-(amino(4-chlorophenyl)(1 -methyl- yl)methyl)-4-(3-chlorophenyl)-l-methyl-2(1H)-quinolinone having an aD 2 0 value of +22.860 (c=49.22 mg/5 ml, methanol) or a pharmaceutically acceptable acid addition salt thereof, at a therapeutically acceptable dose and frequency.

In another embodiment the invention is a method for treating a synucleinopathic subject comprising administering to the synucleinopathic subject a farnesyl transferase inhibitor of the formula:

R

2 R4

R

l

R

3 wherein the dotted line represents an optional bond; oX is oxygen or sulfur; 00 R' and R 2 each independently are hydrogen, hydroxy, halo, cyano, C,.

6 alkyl, trihalomethyl, trihalomethoxy, C 2 6 alkenyl, C,.

6 alkyloxy, hydroxyC,.

6 alkyloxy, C,.

6 alkyloxyCI.

6 alkyloxy,

C,.

6 alkyloxycarbonyl, aminoC,.

6 alkyloxy, mono- or di(C,.

6 alkyl)aminoC,.

6 alkyloxy, Ar 1 Ar'

C,.

6 alkyl, Ar' oxy, Ar' C,.

6 alkyloxy; 31 R and R 4 each independently are hydrogen, halo, cyano, C,.

6 alkyl, C,.

6 alkyloxy, Ar' OXY, C 1 6 IND alkylthio, di(C,.

6 alkyl)amino, trihalomethyl or trihalomethoxy;

R

5 is hydrogen, halo, CI- 6 alkyl, cyano, haloC,.

6 alkyl, hydroxyC,.

6 alkyl, cyanoCI- 6 alkyl, aminoC,.

6 alkyl, C,.

6 alkyloxyC,.

6 alkyl, C,.

6 alkylthioC,.

6 alkyl, aminocarbonylC,.

6 alkyl, C,.

6 alkyloxycarbonylC,.

6 alkyl, C,.

6 alkylcarbonylC,.

6 alkyl, C,.

6 alkyloxycarbonyl, mono- or di(C,.

6 alkyl)aminoCI- 6 alkyl, Ar', Ar' C,.6 alkyloxyCI- 6 alkyl; or a radical of formula: -0-R10(a- I1),

-S-R'

0 2), R 12-3), wherein R1 0 is hydrogen, C,.

6 alkyl, C,.

6 alkylcarbonyl, Ar', Ar 1

C,.

6 alkyl, C,.

6 alkyloxycarbonylC,.

6 alkyl, or a radical of formula Alk--OR'1 3 or Alk--NR'1 4

R'

R" is hydrogen, C 1 6 alkyl, Ar' or Ar' C 1 6 alkyl; R 12is hydrogen, C,.

6 alkyl, C,.

6 alkylcarbonyl, C,.

6 alkyloxycarbonyl, C,.

6 alkylaminocarbonyl, Ar', Ar' C,.

6 alkyl, C,.

6 alkylcarbonyl-C,.

6 alkyl, Ar' carbonyl, Ar' C,.

6 alkylcarbonyl, aminocarbonylcarbonyl, C,.

6 alkyloxyC,.

6 alkylcarbonyl, hydroxy, C,.

6 alkyloxy, aminocarbonyl, di(CI.

6 alkyl)aminoC,.

6 alkylcarbonyl, amino, C,.

6 alkylamino, C,.

6 al kylcarbonyl amino, or a radical or formula Alk--OR'1 3 or Alk--NR' 4 R'1 5 wherein Alk is 6 alkanediyl; R'1 3 is hydrogen, C,.

6 alkyl, C,.

6 alkylcarbonyl, hydroxyC,.

6 alkyl, Ar' or Ar 1

C,.

6 alkyl; R'1 4 is hydrogen, C,.

6 alkyl, Ar' or Ar' C,.

6 alkyl; R'1 5 is hydrogen, C,.

6 alkyl, C,.

6 alkylcarbonyl, Ar' or Ar' C,.

6 alkyl; R 6 is a radical of formula:

N

_Nj

R

16 (b-i1) o I 0 ~1

R

1 6 00 N

R

17 (b-2) wherein

SR

16 is hydrogen, halo, Ar', Cl- 6 alkyl, hydroxyCl-6 alkyl, Ci.

6 alkyloxyCi.6 alkyl, CI-6 alkyloxy, N, 5 Ci- 6 alkylthio, amino, Ci-6 alkyloxycarbonyl, Ci-6 alkylthioCi-6 alkyl, Ci-6 alkylS(O)Ci-6 alkyl or SCi.

6 alkylS(O) 2 Ci.

6 alkyl; 0 R'7 eC\ R is hydrogen, CI- 6 alkyl or di(Ci-4 alkyl)aminosulfonyl;

R

7 is hydrogen or Ci- 6 alkyl provided that the dotted line does not represent a bond;

R

8 is hydrogen, Ci.

6 alkyl or Ar 2

CH

2 or Het' CH 2

R

9 is hydrogen, Cl- 6 alkyl, Cl- 6 alkyloxy or halo; or

R

8 and R 9 taken together to form a bivalent radical of formula -CH=CH- (c-1)

-CH

2

-CH

2 (c-2)

-CH

2

-CH

2

-CH

2 (c-3)

-CH

2 or

-CH

2

-CH

2 Ar' is phenyl; or phenyl substituted with 1 or 2 substituents each independently selected from halo, C.-6 alkyl, CI- 6 alkyloxy or trifluoromethyl; Ar 2 is phenyl; or phenyl substituted with 1 or 2 substituents each independently selected from halo, Ci.

6 alkyl, Ci- 6 alkyloxy or trifluoromethyl; and Het' is pyridinyl; pyridinyl substituted with 1 or 2 substituents each independently selected from halo, Ci- 6 alkyl, Ci- 6 alkyloxy or trifluoromethyl; or a stereoisomeric form or a pharmaceutically acceptable acid or base addition salt form thereof, at a therapeutically effective dose and frequency.

In another embodiment, the invention is a method for treating a synucleinopathic subject comprising administering to the synucleinopathic subject a farnesyl transferase inhibitor of the formula

N

(CH2)n O'J" N H

R

9 wherein n is 2 or 3 and R 2

R

3

R

4 and R 9 are as defined previously, or a stereoisomeric form or a pharmaceutically acceptable acid or base addition salt form thereof, at a therapeutically effective dose and frequency.

In another embodiment the invention is a method for treating a synucleinopathic subject comprising administering to the synucleinopathic subject a farnesyl transferase inhibitor of the formula: wherein the dotted line represents an optional bond; X is oxygen or sulfur; is a bivalent radical of formula: -CH=CH-

-CH

2

-CH

2 o-CH 2

-CH

2

-CH

2 00 -CH 2

-CH

2

-CH

2

-CH

2

-CH

2

-CH

2 -CH=N- or -CO-NH- R1 and R 2 each independently are hydrogen, hydroxy, halo, cyano, C 1 6 alkyl, trihalomethyl, trihalomethoxy, C 2 6 alkenyl, C'1 6 alkyloxy, hydroxy C 1 6 alkyloxy, C 1 6 alkyloxyCI- 6 alkyloxy, 22

C

1 6 alkyl, Ar 2-oxy, Ar 2

CI-

6 alkyloxy; or when on adjacent positions R1 and R 2 taken together may form a bivalent radical of formula:

-O-CH

2 (b-i1),

-O-CH

2

-CH

2 -O-CH=CH-

-O-CH

2

-CH

2

-O-CH

2

-CH

2

-CH

2 or -CH=CH-CH=CH- R 3 and R 4 each independently are hydrogen, halo, cyano, CI- 6 alkyl, C 1 6 alkoxy, Ar 3 -oxy,

C

1 6 alkylthio, di(C 1 6 alkyl)amino, trihalomethyl, trihalomethoxy, or when on adj ecent positions R 3 and R 4 taken together may form a bivalent radical of formula:

-O-CH

2

-O-CH

2

-CH

2 or -CH=CH-CH=CH- R 5 is a radical of formula:

IND

N

o

N

o 1 (d-1) 00

N

R14 (d-2) wherein R is hydrogen, halo, Ar 4

CI-

6 alkyl, hydroxyCj.

6 alkyl, C 1 6 alkyloxyCI- 6 alkyl, CI- 6 alkyloxy, C 1 6 alkylthio, amino, C 1 6 alkyloxycarbonyl, CI- 6 alkylS(O)C 1 6 alkyl or C 16 alkylS(O) 2

C

1 6 alkyl; R 1 4 is hydrogen, C 1 6 alkyl or di(C,4 alkyl)aminosulfonyl; R 6 is hydrogen, hydroxy, halo, C 1 6 alkyl, cyano, haloCI- 6 alkyl, hydroxyC- 1 6 alkyl, cyanoC 1- 6 alkyl, aminoC 1 6 alkyl, C 1 6 alkyloxyC 1 6 alkyl, C 1 6 alkylthioC 1 alkyl, aminocarbonyl-CI- 6 alkyl, CI- 6 alkyloxycarbonylC 1 6 alkyl, C 1 6 alkylcarbonylC 1 6 alkyl, CI- 6 alkyloxycarbonyl, mono- or di(CI.

6 alkyl)aminoC 1 6 alkyl, Ar 5 Ar 5

C

1 6 alkyloxyC 1 6 alkyl; or a radical of formula 1), -S-R or R' wherein R 7 is hydrogen, C 1 6 alkyl, C 1 6 alkylcarbonyl, Ar 6 Ar 6

C

1 6 alkyl, C 1 6 alkyloxycarbonylCI.

6 alkyl, or a radical of formula Alk--OR' 0 or Alk--NR' R1 2 R 8 is hydrogen, C 1 6 alkyl, Ar 7 or Ar 7

C

1 6 alkyl;

R

9 is hydrogen, CI- 6 alkyl, C 14 6 alkylcarbonyl, C 14 6 alkyloxycarbonyl, C 1 6 alkylaminocarbonyl, Ar 8 Ar 8

-C

1 6 alkyl, C 1 6 alkylcarbonyl-C 1 6 alkyl, Ar 8 -carbonyl, Ar 8

C

1 6 alkylcarbonyl, aminocarbonylcarbonyl, C 1 6 alkyloxyC 1 6 alkylcarbonyl, hydroxy, C 1 6 alkyloxy, aminocarbonyl, di(CI- 6 alkyl)aminoC 1 6 alkylcarbonyl, amino, C 1 6 alkylamino, C 1 6 alkylcarbonylamino, or a radical or formula Alk--OR' 0 or Alk--NR'' R" 2 wherein Alk is C,.

6 alkanediyl; R1 0 is hydrogen, CI- 6 alkyl, C 1 6 alkylcarbonyl, hydroxyC 1 6 alkyl, Ar 9 or Ar 9

C

1 6 alkyl;

OR

is hydrogen, CI-6 alkyl, CI-6 alkylcarbonyl, Ar 1 o or Arlo CI- 6 alkyl;

R

1 2 is hydrogen, CI- 6 alkyl, Ar" or Ar" -Ci-6 alkyl; and O Ar' to Ar 1 are each independently selected from phenyl; or phenyl substituted with 00 halo, Ci- 6 alkyl, C.-6 alkyloxy or trifluoromethyl, or a stereoisomeric form or a pharmaceutically acceptable acid or base addition salt form thereof, at a therapeutically effective dose and frequency.

SIn one embodiment, the dotted line represents an optional bond; X is O or S; SR and R 2 are each independently selected from hydrogen, halo, C.-6 alkyl, CI-6 alkyloxy, trihalomethyl or trihalomethoxy;

R

3 and R 4 are each independently selected from hydrogen, halo, C.-6 alkyl, C' 6 alkyloxy, trihalomethyl or trihalomethoxy;

R

5 a radical of formula wherein R 1 3 is hydrogen or R 5 is a radical of formula (d-2) wherein R 13 is hydrogen or C.-6 alkyl and R' 4 is hydrogen or Ci- 6 alkyl; and

R

6 is hydrogen, hydroxy, haloCi.

6 alkyl, hydroxyC.-6 alkyl, cyanoCi.

6 alkyl, CI-6 alkyloxycarbonylCi.

6 alkyl, or a radical of formula -NR 8

R

9 wherein R 8 is hydrogen or Ci-6 alkyl and R 9 is hydrogen, CI- 6 alkyl, CI- 6 alkyloxy or CI- 6 alkyloxyCl-6 alkylcarbonyl.

In another embodiment, the invention is a method for treating a synucleinopathic subject comprising administering to the synucleinopathic subject a farnesyl transferase inhibitor of the formula:

R

2 R4

R

1

R

X N

A

wherein the dotted line represents an optional bond; wherein X, R, R 3 and R 4 are as defined previously;

ID

or a stereoisomeric form or a pharmaceutically acceptable acid or base addition salt form thereof, at a therapeutically effective dose and frequency.

O In another embodiment, the invention is a method for treating a synucleinopathic subject 00 comprising administering to the synucleinopathic subject a farnesyl transferase inhibitor of the formula:

R

3

R

16

N

R2- 7 7R O H N R8 R17

R

18

R

7 X N R19 R6

R

1 or (II) or

R

5

-N

00 N+ R 6 wherein the dotted line represents an optional bond; X is oxygen or sulfur; R' is hydrogen, CI- 12 alkyl, Arl, Ar 2 C1- 6 alkyl, quinolinylC,.

6 alkyl, pyridylC,.

6 alkyl, hydroxyC 1 6 alkyl, C 1.

6 alkyloxyC 1- 6 alkyl, mono- or di (C 1 6 alkyl) aminoC 1- 6 alkyl, aminoC 1- 6 alkyl, or a radical of formula -Alk'1 -Alk' or -Alk' -S (0) 2 wherein Alk' is C1- 6 alkanediyl, R9 is hydroxy, C1- 6 alkyl, C1- 6 alkyloxy, amino, C1.

8 alkylamino or C1-8 alkylamino substituted with C1-6 alkyloxycarbonyl; R 2, R 3 and R 1 6 each independently are hydrogen, hydroxy, halo, cyano, C1- 6 alkyl, C1.

6 alkyloxy, hydroxyC,.

6 alkyloxy, C,- 6 alkyloxyC,.

6 alkyloxy, aminoC,.

6 alkyloxy, mono- or di(C,.

6 alkyl)aminoC1.

6 alkyloxy, Ar', Ar 2

C,-

6 alkyl, Ar 2 oxy, Ar 2 C1- 6 alkyloxy, hydroxycarbonyl, C, -6 alkyloxycarbonyl, trihalomethyl, trihalomethoxy, C 2 6 alkenyl, 4,4dimethyloxazolyl; or when on adjacent positions R 2and R 3taken together may form a bivalent radical of formula

-O-CH

2 (a-i1),

-O-CH

2

-CH

2 (a-2) -O-CH=CH- (a-3)

-O-CH

2

-CH

2 (a-4)

-O-CH

2

-CH

2

-CH

2 or -CH=CH-CH=CH- R 4 and R 5 each independently are hydrogen, halo, Ar', alkyl, hydroxyCI.

6 alkyl, 6 alkyloxyC,.

6 alkyl, 6 alkyloxy, C,.

6 alkylthio, amino, hydroxycarbonyl, 6 o alkyloxycarbonyl, 6 alkylS 6 alkyl or 6 alkylS (0)2 6 alkyl; 00 R 6and R7each idpnetyare hydrogen, halo, cy 6 alkyl, 6 alkyloxy, Ar2oxy, trihalomethyl, C,.

6 alkylthio, di 6 alkyl) amino, or when on adjacent positions R 6 and R 7 taken together may form a bivalent radical of formula -0-CH 2 or -CH=CH-CH=CH- (Ni 8 IND R is hydrogen, 6 alkyl, cyano, hydroxycarbonyl, C 1.- 6 alkyloxycarbonyl, C 1.

6 C) 10 alkylcarbonylC,.

6 alkyl, cyanocC,..

6 alkyl, 6 alkyloxycarbonylC,..

6 alkyl, carboxyC,..

6 alkyl, hydroxyC,..

6 alkyl, aminoC,.

6 alkyl, mono- or di 6 alkyl)-aminoC,..

6 alkyl, imidazolyl, haloC,..

6 alkyl, C,- 6 alkyloxy-C,..

6 alkyl, aminocarbonylC,..

6 alkyl, or a radical of formula -S-R10(b-2), -N-R1 R 12(b-3), wherein R1 0 is hydrogen, 6 alkyl, 6 alkylcarbonyl, Ar', Ar 2 6 alkyl, 6 alkyloxycarbonylC,..

6 alkyl, a radical or formula -Alk 2-OR" or -Alk 2-NR" R' R"1 is hydrogen, 12 alkyl, Ar' or Ar 2 C 1- 6 al kyl; R'1 2 is hydrogen, 6 alkyl, 6 alkylcarbonyl, 6 alkyloxycarbonyl, 6 alkylaminocarbonyl, 1 2 12 Ar Ar 6 alkyl, 6 alkylcarbonylC,..

6 alkyl, a natural amino acid, Ar' carbonyl, Ar 6 alkylcarbonyl, amninocarbonylcarbonyl, C,.

6 alkyloxyC,.

6 alkyl-carbonyl, hydroxy, C,.

6 alkyloxy, aminocarbonyl, di(C1- 6 alkyl)aminoC 1- 6 alkylcarbonyl, amino, 6 alkylamino, 6 alkylcarbonylamino, or a radical of formula -Alk 2 -OR'1 3 or -Alk 2

-NR"

4 R'1 wherein Alk 2 is 6 alkanediyl; R'1 3 is hydrogen, 6 alkyl, 6 alkylcarbonyl, hydroxyC,..

6 alkyl, Ar 1 or Ar 2 6 alkyl; R 1 4 is hydrogen, C,.

6 alkyl, Ar' or Ar 2 6 alkyl; R1 5 is hydrogen, 6 alkyl, 6 alkylcarbonyl, Ar' or Ar 2 6 alkyl; R 1 7 is hydrogen, halo, cyano, 6 alkyl, 6 -alkyloxycarbonyl, Arl R 18is hydrogen, 6 alkyl, 6 alkyloxy or halo;

R'

9 is hydrogen or 6 alkyl; Ar 1 is phenyl or phenyl substituted with 6 alkyl, hydroxy, amino, C,.

6 alkyloxy or halo; and Ar 2is phenyl or phenyl substituted with 6 alkyl, hydroxy, amino, 6 alkyloxy or halo;

IO

Sor a stereoisomeric form or a pharmaceutically acceptable acid or base addition salt form thereof, at a therapeutically effective dose and frequency.

0 0 00 In another embodiment, the invention is a method for treating a synucleinopathic subject comprising administering to the synucleinopathic subject a farnesyl transferase inhibitor of the formula:

NO

S/R1)r (R2)s I 2R 3 Y2 1 X1' N

(R

5 t

X

2

-X

3 wherein =X'-X2-X 3 is a trivalent radical of formula =N-CR6=CR 7

=N-N=CR

6 =N-CR6=N-

=CR

6

-CR

7

=CR

8 =CR6-N=CR 7

=CR

6 or =CR wherein each R 6

R

7 and R 8 are independently hydrogen, C-4 alkyl, hydroxy, CI-4 alkyloxy, aryloxy, C 14 alkyloxycarbonyl, hydroxyC 1 -6 alkyl, C-4 alkyloxyC 1 i 4 alkyl, mono- or di(C 1 -6 alkyl)aminoCi.

4 alkyl, cyano, amino, thio, C-4 alkylthio, arylthio or aryl;

-Y

2 is a trivalent radical of formula

>CH-CHR

9 o>CH-NR 9- or 00 >C=CR 9 wherein each R9~ independently is hydrogen, halo, halocarbonyl, aminocarbonyl, hydroxyC14 alkyl, cyano, carboxyl, C 1 4 alkyl, C14 alkyloxy, C 1 4 alkyloxyC 1 4 alkyl, C 1 4 alkyloxycarbonyl, mono- or di(C 1- 6 alkyl)amino, mono- or di(C 14 alkyl)aminoC 14 alkyl, or aryl; r and s are each independently 0, 1, 2, 3, 4 or IND t is 0, 1, 2 or 3; each R' and R 2 are independently hydroxy, halo, cyano, CI.

6 alkyl, trihalomethyl, trihalomethoxy, C 2 6 alkenyl, C 1 6 alkyloxy, hydroxyCI- 6 alkyloxy, C 1 6 alkylthio, C 1 6 alkyloxyC 16 alkyloxy, C 1 6 alkyloxycarbonyl, aminoC 1 6 alkyloxy, mono- or di(C 1- 6 alkyl)amino, mono- or di(C 1 6 alkyl)aminoC 1 6 alkyloxy, aryl, arylC 1 6 alkyl, aryloxy or arylC 1 6 alkyloxy, hydroxycarbonyl, C 1 6 alkyloxycarbonyl, aminocarbonyl, aminoC 1 6 alkyl, mono- or di(C 1.

6 alkyl)aminocarbonyl, or mono- or di(C 1 6 alkyl)aminoC 1 6 alkyl; or two R1 or R 2substituents adjacent to one another on the phenyl ring independently form together a bivalent radical of formula

-O-CH

2 (a-i1),

-O-CH

2

-CH

2 -0=CH=CH-

-O-CH

2

-CH

2

-O-CH

2

-CH

2

-CH

2 or -CH=CH-CH=CH- R 3 is hydrogen, halo, C 1 6 alkyl, cyano, haloCI- 6 alkyl, hydroxyCI.

6 alkyl, cyanoC 1 6 alkyl, aminoC 1 6 alkyl, CI- 6 alkyloxyC 1 6 alkyl, C 1 6 alkylthioC 1-6 alkyl, aminocarbonyl, C 1 6 alkyl, hydroxycarbonyl, hydroxycarbonylC 1 6 alkyl, C 1 6 alkyloxycarbonylC 1 6 alkyl, CI- 6 alkylcarbonylC 1 6 alkyl, C 1 6 alkyloxycarbonyl, aryl, arylC 1 6 alkyloxyCi 6alkyl, mono- or di(CI- 6 alkyl)aminoC 1 6 alkyl; or a radical of formula -0-R10(b-i1),

-S-R

10 or -NR''R 12(b-3), wherein R 10 is hydrogen, C 1 6 alkyl, C 1 .6 alkylcarbonyl, aryl, arylC 1 6 alkyl, C 1 6 alkyloxycarbonyl C 1 6 alkyl, or a radical of formula -Alk--OR 1 3 or -Alk--NR' 4 R1 5

R

1 1 is hydrogen, C 1 6 alkyl, aryl or arylC 1 6 alkyl; IND2 R 12is hydrogen, C 1 6 alkyl, aryl, hydroxy, amino, C 1 6 alkyloxy, C 1 6 alkylcarbonylC 1 6 __alkyl, arylCI.

6 alkyl, C 1 6 alkylcarbonylamino, mono- or di(CI- 6 alkyl)amnino, C 1 6 alkylcarbonyl,

C.)

00 alkyloxycarbonyl, C 1 6 alkyloxyCI- 6 alkylcarbonyl, mono- or di(CI- 6 alkyl)aminocarbonyl wherein the alkyl moiety may optionally be substituted by one or more substituents independently selected from aryl or C 1 3 alkyloxycarbonyl, aminocarbonylcarbonyl, mono- or di(CI- 6 alkyl)aminoCI- 6 alkylcarbonyl, or a radical of formula -Alk--OR' 3 or -Alk--NR' 4

R'

5 wherein Alk is C 1 6 alkanediyl; (RN1 IND is hydrogen, C 1 6 alkyl, C 1 6 alkylcarbonyl, hydroxyCj.

6 alkyl, aryl or arylCj.

6 alkyl;

R

1 is hydrogen, C 1 6 alkyl, aryl or arylC 1 6 alkyl; R1 5 is hydrogen, C 1 6 alkyl, C 1 6 alkylcarbonyl, aryl or arylC 1 6 alkyl; R 4 is a radical of formula

N

-NN

N

R

1 (c-2) wherein R 1 6 is hydrogen, halo, aryl, C 1 6 alkyl, hydroxyCI- 6 alkyl, C 1 6 alkyloxyCI- 6 alkyl, C 1 6 alkyloxy, C 1 6 alkylthio, amino, mono- or di(CIA4 alkyl)amino, hydroxycarbonyl, C 1 6 alkyloxycarbonyl, C 1 6 alkylthioCI.

6 alkyl, C 1 6 alkylS(O)C 1 6 alkyl or CI.

6 alkylS(O) 2

C

1 6 alkyl; R 1 7 is hydrogen, C 1 6 alkyl, C 1 6 alkyloxyC 16 alkyl, arylC 1 6 alkyl, trifluoromethyl or di(C 1 4 alkyl)aminosulfonyl;

R

5 is C 1 6 alkyl C 1 6 alkyloxy or halo; aryl is phenyl, naphthalenyl or phenyl substituted with one or more substituents each independently selected from halo, C 1 6 alkyl, C 1 6 alkyloxy or trifluoromethyl; with the proviso that that when R 1 6 is bound to one of the nitrogen atoms in the imidazole ring of formula or R1 is hydrogen, aryl, C 1 6 alkyl, hydroxyC 1 6 alkyl,

C

1 6 alkyloxyCI- 6 alkyl, C 1 6 alkyloxycarbonyl, C 1 6 alkylS(O)C 1 6 alkyl or C 1 6 alkylS(O) 2

C

1 6 alkyl; or a stereoisomeric form or a pharmaceutically acceptable acid or base addition salt form thereof, at a therapeutically effective dose and frequency.

o In one embodiment, each R' and R2 are independently hydroxy, halo, cyano, C 1 6 alkyl, 00 trihalomethyl, trihalomethoxy, C 2 6 alkenyl, C1- 6 alkyloxy, hydroxyCi- 6 alkyloxy, C1- 6 alkylthio, C 1 alkyloxyC 1 6 alkyloxy, C 1 6 alkyloxycarbonyl, arninoC 1 6 alkyloxy, mono- or di(C 1 6 alkyl)amino, mono- or di(C,- 6 alkyl)aminoC 1 6 alkyloxy, aryl, arylC,- 6 alkyl, aryloxy or arylC,- 6 alkyloxy, hydroxycarbonyl, or C1- 6 alkyloxycarbonyl; or two R' or R 2 substituents adjacent to one another on the phenyl ring independently form IND together a bivalent radical of formula

-O-CH

2

I),

-O-CH

2

-CH

2 -0=CH=CH-

-O-CH

2

-CH

2

-O-CH

2

-CH

2

-CH

2 or -CH=CH-CH=CH- R 1 7 is hydrogen, C1- 6 alkyl, trifluoromethyl or di(C,.

6 alkyl)aminosulfonyl; with the proviso that that when R 1 6 is bound to one of the nitrogen atoms in the imidazole ring of formula R 1 6 is hydrogen, aryl, C1- 6 alkyl, hydroxyC 1 6 alkyl, C1- 6 alkyloxyC 1 6 alkyl, C1- 6 alkyloxycarbonyl, C 1 6 alkylS(O)C,.

6 alkyl or C 1 6 alkylS(O) 2 C1- 6 alkyl.

In another embodiment, the invention is a method for treating a synucleinopathic subject comprising administering to the synucleinopathic subject a famnesyl transferase inhibitor of the formula: wherein the dotted line represents an optional bond; o X is oxygen or sulfur; 00 R' is hydrogen, CI, 2 alkyl, Arl, Ar 2

C,.

6 alkyl, quinolinylC- 6 alkyl, pyridylC,-6alkyl, hydroxyC, 6 alkyl,C C.

6 alkyloxyC,.

6 alkyl, mono- or di(C- 6 alkyl)aminoC,-6alkyl, aminoC,.

6 alkyl, or a radical of formula or -Alk'-S(O) 2

-R

9 wherein Alk' is C,-6alkanediyl, R9 is hydroxy,C C- 6 alkyl,C C.

6 alkyloxy, amino, C,.

8 alkylamino or C,.

8 alkylamino substituted IND with C,.

6 alkyloxycarbonyl;

R

2 and R 3 each independently are hydrogen, hydroxy, halo, cyano, C,.

6 alkyl, C,.

6 alkyloxy, hydroxyCl.

6 alkyloxy, C,.

6 alkyloxyC,.

6 alkyloxy, aminoC,.

6 alkyloxy, mono- or di(CI- 6 1 2 2 2 alkyl)aminoC,.

6 alkyloxy, Ar Ar alkyl, Ar oxy, Ar C,.

6 alkyloxy, hydroxycarbonyl, C,.

6 alkyloxycarbonyl, trihalomethyl, trihalomethoxy, C 2 6 alkenyl; or when on adjacent positions R 2 and R 3 taken together may form a bivalent radical of formula

-O-CH

2

I),

-O-CH

2

-CH

2 -O-CH=CH-

-O-CH

2

-CH

2

-O-CH

2

-CH

2

-CH

2 -CH=CH-CH=CH- R 4 and R 5 each independently are hydrogen, Ar', C,.

6 alkyl,C C.

6 alkyloxyCl- 6 alkyl, C,.

6 alkyloxy,C C 1 6 alkylthio, amino, hydroxycarbonyl,C C 1 6 alkyloxycarbonyl, C,.

6 alkyIS(O)CI.

6 alkyl or C,.

6 alkylS(O) 2

C,.

6 alkyl; R 6 and R 7 each independently are hydrogen, halo, cyano, C,.

6 alkyl, C,.

6 alkyloxy or Ar 2 oxy;

R

8 is hydrogen, C,.

6 alkyl, cyano, hydroxycarbonyl,C C.

6 alkyloxycarbonyl, C1- 6 alkylcarbonylC,.

6 alkyl, cyanoC,.

6 alkyl, C,.

6 alkyloxycarbonylC,.

6 alkyl, hydroxycarbonylC.

6 alkyl, hydroxyC,.

6 alkyl, aminoC,.

6 alkyl, mono- or di(CI.

6 alkyl)arninoC,.

6 alkyl, haloC,.

6 alkyl, C,.

6 alkyloxyC].

6 alkyl, aminocarbonylC,.

6 alkyl, Ar 1 Ar 2

C,.

6 alkyloxyC,.

6 alkyl, C1.

6 alkylthioC,.

6 alkyl;

R

10 is hydrogen, C,.

6 alkyl, C,.

6 alkyloxy or halo; R" is hydrogen or C,.

6 alkyl; Ar' is phenyl or phenyl substituted with C,.

6 alkyl, hydroxy, amino,C C,.

6 alkyloxy or halo; and Ar 2is phenyl or phenyl substituted with C 1 6 alkyl, hydroxy, amnino, C,.

6 alkyloxy or halo, or a stereoisomeric form or a pharmaceutically acceptable acid or base addition salt form thereof, at a therapeutically effective dose and frequency.

In another embodiment, the invention is a method for treating a synucleinopathic subject comprising administering to the synucleinopathic subject a farnesyl transferase inhibitor with of formula:

R

3 wherein the radicals R 2

R

3 R4, R 5

R

6 R, Rs, Rio and R 1 are as defined above, or a stereoisomeric form or a pharmaceutically acceptable acid or base addition salt form thereof, at a therapeutically effective dose and frequency.

In another embodiment, the invention is a method for treating a synucleinopathic subject comprising administering to the synucleinopathic subject a famesyl transferase inhibitor with the formula: wherein the radicals R 2

R

3

R

4 Rs, R 6

R

7 Rs, Rio and R 1 1 are as defined above, or a

ID

O stereoisomeric form or a pharmaceutically acceptable acid or base addition salt form thereof, at a therapeutically effective dose and frequency.

O In one aspect of the invention is a method of treating a synucleinopathic subject is 00 provided, the method comprising, administering to a synucleinopathic subject a farnesyl transferase inhibitor compound of the formula: B C R4, R B

D

N

/Y K

N--Z--R

8 N Rr -Ss-Tt

R

6

R

7

I

R

4

R

B-

x

N-Z-R

8

N

N R r Ss T t

R

6 R7V R R 2

R

3

R

6

R

7

B

C

R

4

R

A

R

4

R

Y

N~ Rr-Ss-Tt

R

6

R

7 or a stereoisomeric form, or a pharmaceutically acceptable acid or base addition salt form thereof, in a therapeutically effective amount, wherein m,n,r,s and t are 0 or 1; p is 0, 1 or 2; V, W and X are selected from the group consisting of oxygen, hydrogen, R 2 or R 3 Z and Y are selected from the group consisting of CHR 9

SO

2

SO

3 CO, CO2, O, NR i0

SO

2

NR",

CONR

2 O CN cI N O SCN II O N -N-S 2

R

13 R14 0 S 2 S-N-N- O NR 20

R

2 1 N NR 22

R

16

R

17

R

18

R

19

S

or Z may be absent; R 6

R

7

R

9 R R 12

R

13 R5, R 1 R, R R1, R R 2

R

2 2

R

24 R R2, R 2

R

2

R

2

R

2

R

2 R, R31, R 32

R

33

R

34

R

3

R

3 R, and R are selected from the group consisting of hydrogen, lower alkyl, substituted alkyl, aryl, or substituted aryl; R 4

R

5 are selected from the group consisting of hydrogen, halo, nitro, cyano and U-R 23 U is selected from the group consisting of sulfur, oxygen, NR 24 CO, SO, SO2, CO2, NR 25

CO

2

NR

26

CONR

2 7

NR

28 SO2, NR 29 SO2 NR 30 SO2 NR 31

NR

3 2 CO, CONR 33

PO

2

R

34 and P0 3

R

35 or U is absent; R 2 and R 3 are selected from the group consisting of hydrogen, alkyl, alkoxycarbonyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, aralkyl, cycloalkyl, aryl, substituted aryl, heterocyclo, substituted heterocyclo, cyano, carboxy, carbamyl CONH 2 or substituted carbamyl further selected from CONH alkyl, CONH aryl, CONH aralkyl or cases where there are two substituents on the nitrogen selected from alkyl, aryl or aralkyl; R 8 and R 2 3 are selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, aralkyl, cycloalkyl, aryl, substituted aryl, heterocyclo, substituted heterocyclo; any two of

R

2 and R 3 can be joined to form a cycloalkyl group; R, S and T are selected from the group consisting of CH 2 CO and CH(CH 2 )pQ wherein Q is NR 36

R

37

OR

38 or CN; and A, B, C and D are carbon, oxygen, sulfur or nitrogen with the provisos that: 1. When m is zero then V and W are not both oxygen or, 2. W and X together can be oxygen only ifZ is either absent, 0, NR 1 0

CHR

9 0 N-S2-- R14 or R 1 in formulas I and II, and V and X together can be oxygen only ifY is O, NR 1 0

CHR

9

TNC;

R

14

-N-SO

2 in formulas III and IV or, 3. R 23 may be hydrogen except when U is SO, SO2, NR 25

CO

2 or

NR

28

SO

2 or, 4. R 8 may be hydrogen except when Z is SO 2 CO2, or

N-SO

2 O NR 2 0 R21N NR 2 2 In one embodiment, the invention is a method of treating a synucleinopathic subject, the method comprising, administering to a synucleinopathic subject a farnesyl transferase inhibitor compound of the formula:

R

4

R

B C D

AX

N-Z-R

8 N Rr-Ss-Tt m

N

RrSsTt V R 1

R

2

R

3

R

6

R

7 or a stereoisomeric form, or a pharmaceutically acceptable acid or base addition salt form thereof, in a therapeutically effective amount, wherein n is 1; r, s and t are 0 or 1; p is 0, 1 or 2; V, W and X are selected from the group consisting of oxygen, hydrogen, R 2 and R 3

ID

S/CN

SN O /c/ CN N SN -N-S 2 C- R 13 R14 0

-C-N-

N

-2 S N 0 NR 20

R

2 1 N NR 22

R

1 6

R

1 7

R

1 8

R

1 9

S

IO

N Z and Y are selected from the group consisting of CHR 9

SO

2 SO3, CO, C0 2 O, NR i0

SO

2 NR", CONRI2, or Z may be absent; R 6

R

7

R

9

R

1 R RI R, R 6

R

7

R

1 8

R

19

R

20 R21, R 22

R

24

R

25

R

26

R

28

R

29

R

30 R31, R 32

R

33

R

34

R

3 5

R

36 R, and R 38 are selected from the group consisting of hydrogen, lower alkyl, substituted alkyl, aryl and substituted aryl; R 4 and R 5 are selected from the group consisting of hydrogen, halo, nitro, cyano and U--R 23 U is selected from the group consisting of sulfur, oxygen, NR 24

CO,

SO, SO 2 C0 2

,NR

25 CO2, NR 26

CONR

27

NR

28

SO

2

NR

29 SO2 NR 30

SO

2

NR

31

NR

32

CO,

CONR

33 P0 2

R

34 and P0 3

R

35 or U is absent; R 2 and R 3 are selected from the group consisting of hydrogen, alkyl, alkoxycarbonyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, aralkyl, cycloalkyl, aryl, substituted aryl, heterocyclo, substituted heterocyclo, cyano, carboxy, carbamyl and substituted carbamyl; R 8 and R 23 are selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, aralkyl, cycloalkyl, aryl, substituted aryl, heterocyclo and substituted heterocyclo; any two of R 2 and R 3 may be joined to form a cycloalkyl group; R, S and T are selected from the group consisting of CH 2 CO and CH(CH 2 )pQ wherein Q is NR 36

R

37

OR

38 or CN; and A, B, C and D are carbon; with the provisos that V and W are not both oxygen; W and X together may be oxygen only if Z is either absent, O,

NR'

i

CHR

9

N(R'

4

N(R

1 S)--S0 2

R

23 may be hydrogen except when U is SO, SO2, NR 25

CO

2 or NR 28

SO

2 and R 8 may be hydrogen except when Z is SO2, C0 2 N(R")--SO2, 0 NR 20

R

21 N NR 22 or In yet another embodiment of the invention the compound is selected from the group __consisting of: o 2,3,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-4-(l -naphthalenylcarbonyl)- I H- 1,4- 00 benzodiazepine, hydrochloride; 8-Chloro-2,3 ,4,5-tetrahydro-l1-( IH-imidazol-4-ylmethyl)-4-( 1-naphthalenylcarbonyl)- IH- 1 ,4-benzodiazepine, hydrochloride; 2,3,4,5-Tetrahydro-4-( I H-imidazol-4-yl-methyl)- 1 -(1-1I -naphthalenylcarbonyl)- 1 H- 1,4benzodiazepine, dihydrochioride; 2,3 ,4,5-Tetrahydro- 1 H-imidazol-4-yl-methyl)-2-methyl-4-( I -naphthalenylcarbonyl)- I1-H- C) 10 1 ,4-benzodiazepine, hydrochloride; 2,3,4,5-Tetrahydro-4-( I-naphthalenylcarbonyl)-1- -(phenylmethyl)-I 1 yllmethyl]- I H-i ,4-benzodiazepine, hydrochloride; 2,3 ,4,5-Tetrahydro-( 1 H-imidazol-4-yl-methyl)-4-( I -naphthalenylsulfonyl)- I H- 1,4benzodiazepine, hydrochloride; ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-3-[2-(methylthio)ethyl]-4-( 1naphthalenylcarbonyl)- 1 H-i ,4-benzodiazepine, hydrochloride; 2,3 ,4,5-Tetrahydro-l1-(1 H-imidazol-4-yl-methyl)-N-methyl-N-phenyl-4H- I,4benzodiazepine-4-carboxamide, hydrochloride; 2-[2,3 ,4,5-Tetrahydro- 1 H-imidazol-4-yl-methyl)- I H-i ,4-benzodiazepin-4yl]sulfonyl]benzoic acid, methyl ester, hydrochloride; 7-Bromo-2,3,4,5 -tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-4-( I-naphthalenylcarbonyl)- 1 H- 1 ,4-benzodiazepine, hydrochloride; 2,3 ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-4-(1 -naphthalenenylcarbonyl)-7-phenyl- 1 H-i ,4-benzodiazepine, hydrochloride; 2,3 ,4,5-Tetrahydro- 1 H-imidazol-2-ylmethyl)-4-( 1 -naphthalenylcarbonyl)- I H-I ,4benzodiazepine, d ihydrochloride; 2,3 ,4,5-Tetrahydro-l1-[3-( 1H-imidazol-2-yl)propyl]-4-( 1-naphthalenylcarbonyl)-l1H- 1,4benzodiazepine, dihydrochioride; I -[3-Amino-3-( 1 H-imidazol-2-yl)propyl]-2,3 ,4,5-tetrahydro-4-( I -naphthalenylcarbonyl)- 1 H-I ,4-benzodiazepine, trihydrochloride; 2,3 ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-3-methyl-4-( 1 -napthalenylcarbonyl)- I H- 1 ,4-benzodiazepine, hydrochloride; ,4,5-Tetrahydro-lI-(1 H-imidazol-4-ylmethyl)-3-[2-(methylthio)ethyl]-4-( 1naphthalenylmethyl)- I H-i ,4-benzodiazepine, hydrochloride; IND 2,3 ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-9-methyl-4-( I -naphthalenylcarbonyl)- I H- I ,4-benzodiazepine, di hydrochloride; o 2,3 ,4,5-Tetrahydro-4-( I H-imidazol-4-ylmethyl)-9-methyl- I -naphthalenylcarbonyl)- 1 H- 0 1 ,4-benzodiazepine, dihyrdochioride; 1 -[[2-(2-Aminoethyl)- 1 H-imidazol-4-yllmethyl]-2,3 ,4,5-tetrahydro-4-( 1naphthalenylcarbonyl)- 1 H-i ,4-benzodiazepine, trihydrochioride; 1 -[[2-Aminomethyl)- 1 H-imidazol-4-yI]methyl]-2,3 ,4,5-tetrahydro-4-( 1naphthalenylcarbonyl)- I H-I ,4-benzodiazepine, trihydrochioride; IND N-[2,3,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-4-( 1 -naphthalenylcarbonyl)- 1 H- 1,4benzodiazepin-8-yI]acetamide, dihydrochioride; 2,3 ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-4-( 1 -naphthal enylcarbonyl)- 8-nitro- 1 Hl- 1,4benzodiazepine, d ihydrochloride; 2,3,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-4-( 1 -naphthalenylcarbonyl)-8-amino- 1 Hl- 1 ,4-benzodiazepine, dihydrochioride; N-[2,3 ,4,5-Tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-4-( I-naphthalenylcarbonyl)- I H- 1,4benzodiazepin-8-y1] benzamide, dihydrochioride; N-[2,3 ,4,5-Tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-4-( 1-naphthalenylcarbonyl)- 1 H- 1,4benzodiazepin-8-yl]cyclohexanamide, dihydrochioride; 2,3,4,5-Tetrahydro-l1-[2-( IH-imidazol-4-yl)ethyl]-4-( I-naphthalenylcarbonyl)- 1 H- 1,4benzodiazepine, dihydrochioride; 2,3,4,5-Tetrahydro- 1 1 H-imidazol-4-yl)ethyl]-4-( I -naphthalenylcarbonyl)-7-phenyl- 1 H- I ,4-benzodiazepine, dihydrochioride; 7-Bromo-2,3 ,4,5-tetrahydro- 1 1 H-imidazol-4-yI)ethyl]-4-( 1 -naphthalenylcarbonyl)- 1 H- 1 ,4-benzodiazepine, d ihydrochloride; 1 -(2-Aminoethyl)- 1H-imidazol-5-yl]methyl]-2,3,4,5-tetrahydro-4-( 1naphthalenylcarbonyl)-7-phenyl- 1 Hl-i ,4-benzodiazepine, trihydrochioride; 2,3,4,5-Tetrahydro- I H-imidazol-4-ylmethyl)-7-phenyl- 1 H-i ,4-benzodiazepine-4carboxylic acid, phenylmethyl ester; 2,3,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-7-phenyl-4-[2-(trifluoromethoxy)benzoyl]- 1 H-i ,4-benzodiazepine; 1,2,3 ,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-N-methyl-N,7-diphenyl-4H- I ,4benzodiazepine-4-carboxamide, dihydrochioride; 2,3,4,5 ,-Tetrahydro- 1 H-imidazol-4-ylmethyl)-4-( 1 -naphthaleneylcarbonyl)-7-( 1piperidinylsulfonyl)- 1 H-i ,4-benzodiazepine, monohydrochioride; 2,3 ,4,5-Tetrahydro- I H-imidazol-4-ylmethyl)-4-( 1 -naphthalenylcarbonyl)-7-pyridin-2-yl- 1 H-i ,4-benzodiazepine, trihydrochioride;

C)

00 1 H-I ,4-benzodiazepine, dihydrochioride; 2,3 ,4,5-Tetrahydro- I H-imidazol-4-ylmethyl)-4-( 1 -naphthalenylcarbonyl)-7-(2-thienyl)- 1 H-I ,4-benzodiazepine, dihydrochioride; 2,3 ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-4-( 1 -naphthalenylcarbonyl)-7-(4pyridinyl)- 1 H-i ,4-benzodiazepine, trihydrochioride; IND2,3 ,4,5-Tetrahydro- 1 H-imidazol-2-yl)propyl]-4-( I -naphthalenylcarbonyl)-7-phenyl- C) 10 1 H-I ,4-benzodiazepine, dihydrochioride; 7-Bromo-2,3 ,4,5-tetrahydro-4-( 1 H-imidazol-4-ylmethyl)- I -naphthalenylcarbonyl)- 1 H- 1 ,4-benzodiazepine, dihydrochioride; 8 -Chi oro-2,3 ,4,5 -tetrahydro-4-( 1 H-imidazol-4-ylmethyl)- 1 -naphthalenylcarbonyl)- I H- 1 ,4-benzodiazepine, d ihydrochloride; 2,3 ,4,5-Tetrahydro-4-( 1 H-imidazol-4-ylmethyl)- 1 -naphthalenylcarbonyl)-7-phenyl- 1 H- 1 ,4-benzodiazepine, hydrochloride; 2,3,4,5-Tetrahydro- I ,4-bis( I H-imidazol-4-ylmethyl)-7phenyl- I H-i ,4-benzodiazepine, dihydrochioride; 2,3 ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-4-( 1 -naphthalenylmethyl)-7-phenyl- 1 H- 1 ,4-benzodiazepine, trifluoroacetate; 2,3,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-7-methoxy-4-( 1 -naphthalenylcarbonyl)- 1 H- 1 ,4-benzodiazepine, dihydrochioride; 2,3,4,5 -Tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-4-( 1-naphthalenylcarbonyl)- I H- 1,4benzodiazepine-7-carboxyl ic acid, dihydrochioride; 2,3,4,5-Tetrahydro- 1-(1 H-imidazol-5-ylmethyl)-4-( 1-naphthalenylcarbonyl)-7-cyclohexyl- 1 H-I ,4-benzodiazepine, 2.5 hydrochloride; 7-Butyl-2,3 ,4,5-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-4-( 1-naphthalenylcarbonyl)- 1H- 1,4benzodiazepine, d ihydrochloride; I [2-(2-Aminoethyl)- 1H-imidazol-4-yllmethyl]-2,3,4,5-tetrahydro-4-( 1naphthalenylcarbonyl)-7-phenyl- 1 H-I ,4-benzodiazepine, trihydrochioride; 1 -[[2-(Aminomethyl)- 1H-imidazol-4-yl]methyl]-2,3 ,4,5-tetrahydro-4-( 1naphthalenylcarbonyl)-7-phenyl- 1 H-i ,4-benzodiazepine, tri hydrochloride; 2,3 ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-4-( 1 -naphthalenylcarbonyl)-8- [N,Nbis(phenyl-methyl)amino]- 1 H-i ,4-benzodiazepine, trihydrochioride; N-[2,3,4,5-Tetrahydro- I H-imidazol-4-yi-methyl)-4-( 1 -naphthalenylcarbonyl)- I H- 1,4benzodiazepin-8-yI]phenylsulfonamide, dihydrochioride; o N-Phenyl-2,3,4,5-tetrahydro- 1 H-imidazol-4-yI-methyl)-4-( I -naphthalenylcarbonyl)- I H- 00 1 ,4-benzo-diazepine-7-carboxamide, dihydrochioride; N-[2,3 ,4,5-Tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-4-( 1 -naphthalenylcarbonyl)- 1 H- 1,4benzodiazepin-8-yl]-3-methylbenzamide, dihydrochioride; N-[2,3 ,4,5-Tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-4-( I-naphthalenylcarbonyl)- IH- 1,4benzodiazepin-8-yl]-4-methylbenzamide, dihydrochioride; 3 -Chiloro-N- [2,3 ,4,5 -tetrahydro- 1 H-imidazol-4-yl-methyl)-4-( I -naphthalenylcarbonyl)- 1 H-I ,4-benzo-diazepin-8-yllbenzamide, dihydrochioride; 7-Bromo-2,3 ,4,5,-tetrahydro- 1 -[[2-[(dimethylamino)-methyl]- I H-imidazol-4-yI]methyl]-4- (1 -naphthalenylcarbonyl)- I H-I ,4-benzodiazepine, dihydrochioride; 7-(4-Chlorophenyl)-2,3,4,5-tetrahydro- 1 H-imidazoi-4-ylmethyl)-4-( 1naphthalenylcarbonyl)- I H-i ,4-benzodiazepine, dihydrochioride; 7-(3-Aminophenyl)-2,3,4,5-tetrahydro- I H-imidazol-4-ylmethyl)-4-( 1naphthalenylcarbonyl)- 1 H-i ,4-benzodiazepine, trihydrochioride; I -Methyl-N-[2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-4-( I -naphthalenylcarbonyl)- 1 H-i ,4-benzodiazepin-8-yi]-i H-pyrrole-2-carboxamide, trihydrochioride; N-[2,3,4,5-Tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-4-( I-naphthalenylcarbonyl)- 1H- 1,4benzodiazepin-8-yl] -3 -furancarboxamide, dihydrochioride; 7-(3-Chlorophenyl)-2,3,4,5-tetrahydro-lI-(1 H-imidazol-4-ylmethyl)-4-( 1naphthalenylcarbonyl)- 1 H-i ,4-benzodiazepine, dihydrochioride; 2-Methyl-N-[2,3 ,4,5-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-4-(l1-naphthalenylcarbonyl)- 1 H-i ,4-benzodiazepin-8-yl]benzamide, dihydrochioride; N-Phenyl-N'-[2,3 ,4,5-tetrahydro- 1 I H-imidazol-4-ylmethyl)-4-( 1 -naphthalenylcarbonyl)- 1 Hl-i ,4-benzodiazepin-8-yI]urea, dihydrochioride; 2,3 ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-4-( 1 -naphthalenylcarbonyl)-7-(3pyridinyl)- 1 H-i ,4-benzodiazepine, trihydrochioride; 2,3 ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-9-methoxy-4-( I -naphthalenylcarbonyl)- I H- 1 ,4-diazepine, dihydrochioride; ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-3-[2-(methylthio)ethyl]-4-( I naphthalenylcarbonyl)- 1 H-I ,4-benzodiazepine, hydrochloride; 2,3 ,4,5-Tetrahydro- I H-imidazol-4-ylmethyl)-4-( 1 -naphthalenylcarbonyl)-3- (phenylmethyl)- I H-i ,4-benzodiazepine, hydrochloride; 38 2,3 ,4,5-Tetrahydro-3-(2-hydroxyethyl)- 1 H-imidazol-4-ylmethyl)-4-( 1naphthalenylcarbonyl)-1I H-i ,4-benzodiazepine, trifluoroacetate; o 2,3 ,4,5-Tetrahydro-4-( 1 H-imidazol-4-ylmethyl)-3-[2-(methylthio)ethyl]-4-( 1- 00 naphthalenylcarbonyl)- 1 H-i ,4-benzodiazepine, trifluoroacetate; ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-4-( I -naphthalenylcarbonyl)-3- (phenylmethyl)- 1 H-I ,4-benzodiazepine, trifluoroacetate; 4-Acetyl-7-bromo-2,3,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-3-(phenylmethyl)- 1 H- 1 ,4-benzodiazepine, hydrochloride; ID2,3,4,5-Tetrahydro-4-( IH-imidazol-4-ylmethyl)- 1-(1 -naphthalenylcarbonyl)-3 (phenylmethyl)- IH-I ,4-benzodiazepine, 1.5 hydrochloride; 7-Bromo- 1,2,3 ,5-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-3-(phenylmethyl)-4H- 1,4benzodiazepine-4-carboxamide, trifluoroacetate; 7-Bromo-2,3,4,5-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-4-(methylsulfonyl)-3- (phenylmethyl)- I H-i ,4-benzodiazepine, hydrochloride; 4-Acetyl-2,3 ,4,5-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-7-phenyl-3 -(phenylmethyl)- 1H- 1 ,4-benzodiazepine, trifluoroacetate; 4-Acetyl-7-bromo-3 -[(4-chlorophenyl)methyl]-2,3 ,4,5-tetrahydro- 1 -m idazol-4ylmethyl)- I H-i ,4-benzodiazepine, dihydrochioride; N-Cyclohexyl-N'-[2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-4-( 1naphthalenylcarbonyl)-1 H-1,4-benzodiazepin-8-yl]urea, dihydrochioride; 2,2-Dimethyl-N-[2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-4-( 1naphthalenylcarbonyl)- 1 H-i ,4-benzodiazepin-8-yi]propanamide, d ihydrochloride; 2,3,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-4-( 1 -naphthalenylsulfonyl)-7-phenyl- 1 Hl- 1 ,4-benzodiazepine, monohydrochioride; 4-Acetyl-7-bromo-2,3 ,4,5-tetrahydro- IH-imidazol-4-ylmethyl)-3 naphthalenylmethyl)- 1 H-I ,4-benzodiazepine, dihydrochioride; 4-Acetyl-7-bromo-2,3 ,4,5-tetrahydro- IH-imidazol-4-ylmethyl)-3 naphthalenylmethyl)- I H-i ,4-benzodiazepine, dihydrochioride; 7-(2-Chlorophenyl)-2,3,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-4-( 1naphthalenylcarbonyl)- I H-I ,4-benzodiazepine, dihydrochioride; 2,3,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-7-phenyl- 1 H-i ,4-benzodiazepine, monohydrochioride; 1 -Methyl-N-[2,3 ,4,5-tetrahydro- I H-imidazol-4-ylmethyl)-4-( 1 -naphthalenylcarbonyl)- 1 H-i ,4-benzodiazepin-8-yI]-2-piperidinecarboxamide, trihydrochioride; N-[2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-4-( I -naphthalenylcarbonyl)- I H- 1,4benzodiazepin-8-yl]-4-morpholinecarboxamide, dihydrochioride; o ,4,5-Tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-4-( 1-naphthalenylcarbonyl)- 1 H- 1,4- 00 benzodiazepin-8-yl]-3-methylbutanamide, dihydrochioride; 1,2,3 ,5-Tetrahydro- 1 H-imidazol-4-ylmethyi)-N,N,7-triphenyl-4H- 1,4-2 benzodiazepine-4-carboxamide, dihydrochioride; 2,3 ,4,5-Tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-7-phenyl-4-[(4-phenyl-1I,2,3-thiadiazol-5yl)carbonyl]-1 H-I ,4-benzodiazepine, trifluoroacetate; 8 [(Cyclohexyl amino)carbonyi] amino] -2,3,4,5 -tetrahydro- 1 H-i mi dazol-4-yl methyl)-3 C) 10 (phenylmethyl)- I H-i ,4-benzodiazepine-4-carboxylic acid, 1, 1 -dimethylethyl ester; 2,3 ,4,5-Tetrahydro- 1 I H-i midazol-4-yl methyl)- 8- [[(4-methyl phenyl)sul fonyl ]amino] -3 (phenylmethyl)- I H-i ,4-benzodiazepine-4-carboxylic acid, 1, 1 -dimethylethylester; 7-Bromo- 1,2,3 ,4-tetrahydro- 1 H-imidazol-4-ylmethyl)-3-(phenylmethyl)-5H- 1,4di hydrochloride; 2,3 ,4,5-Tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-4-[ 1-oxo-3-( 1-piperidinyl)propyl]-7phenyl- 1 H-i ,4-benzodiazepine, trihydrochioride; 2,3 ,4,5-Tetrahydro-lI-(I H-imidazol-4-ylmethyi)-7-phenyl-4-(4-quinolinylcarbonyl)- 1 H- 1,4benzodiazepine, tri hydrochloride; 4-[(5-Bromo-3-pyridinyl)carbonyl]-2,3 ,4,5-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-7phenyl- 1 H-i ,4-benzodiazepine, trihydrochioride; (S)-4-[2-(Dimethyiamino)- 1 -oxo-3-phenylpropyI]-2,3 ,4,5-tetrahydro- 1 H-imidazol-4ylmethyl)-7-phenyl- I H-i ,4-benzodiazepine, trihydrochioride; 2,3 ,4,5-Tetrahydro-4-1j4-hydroxy-3-(4-morpholinyl-methyl)benzoyl]- 1 H-imidazol-4ylmethyl)-7-phenyl- 1 Hl-i ,4-benzodiazepine, trihydrochioride; ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-4-[( 1 -methyl-2-pyrrolidinyl)carbonyl]- 7-phenyl- 1 H-i ,4-benzodiazepine, trihydrochioride; 2,3,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-7-phenyl-4-[[2-(propylthio)-3pyridinyljcarbonyl]- 1 H-i ,4-benzodiazepine, trihydrochioride; 4-[(2-Chloro-6-methyl-4-pyridinyl)carbonyl]-2,3 ,4,5-tetrahydro- 1 H-imidazol-4ylmethyl)-7-phenyi- 1 H-i ,4-benzodiazepine, trihydrochioride; 2,3 ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-7-phenyl-4-[[2-(phenylthio)-3pyridinyl]carbonyl]- 1 H-i ,4-benzodiazepine, trihydrochioride; 2,3 ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-4-[[2-(4-methylphenoxy)-3 pyridinyl]carbonyl]-7-phenyl- 1H-I ,4-benzodiazepine, trihydrochioride; 2,3 ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-4-[(2-methoxy-3-pyridinyl)carbonyl]-7phenyl-l1H-I ,4-benzodiazepine, trihydrochioride; o 2,3 ,4,5-Tetrahydro- 1 I H-imidazol-4-ylmethyl)-7-phenyl-4-[(5-phenyl-4- 00 oxazolyl)carbonyl]- 1H-i ,4-benzodiazepine, dihydrochioride;- 4-Acetyl-2,3 ,4,5-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-7-phenyl- 1H-i ,4-benzodiazepine, dihydrochloride; 2,3,4,5 -Tetrahydro- 1 H-imidazol-4-ylmethyl)-7-phenyl-4- [(tetrahydro-3 furanyl)carbonyl] -1H-i ,4-benzodiazepine, dihydrochioride; IND 2,3 ,4,5-Tetrahydro- I H-imidazol-4-ylmethyl)-4-[(2-methoxyethoxy)acetyl]-7-phenyl- 1 Hl- C) 10 1 ,4-benzodiazepine, d ihydrochloride; 2,3,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-4-[4-(4-morpholinylmethyl)benzoyl]-7phenyl- I H-i ,4-benzodiazepine, trihydrochioride; 2,3 ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-4-[4-(methylsulfonyl)benzoyl]-7-phenyl- 1 H-I ,4-benzodiazepine, dihydrochioride; 2,3 ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyi)-4-[ 1 -oxo-3-(phenylsulfonyl)propyl]-7phenyl- I H-i ,4-benzodiazepine, dihydrochioride; 2,3,4,5-Tetrahydro- I H-imidazol-4-ylmethyl)-7-phenyl-4-(3 -pyridinylacetyl)- 1 H- 1,4benzodiazepine, trihydrochioride; 2,3,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-7-phenyl-4-(2-quinoxalinylcarbonyl)- 1 Ho 1 ,4-benzodiazepine, tetrahydrochioride; 2,3,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-4-(4-isoquinolinylcarbonyl)-7-phenyl-H- 1 ,4-benzodiazepine, trihydrochioride; 4-[(2-Chloro-3 -pyridinyl)carbonyl]-2,3 ,4,5-tetrahydro- 1-(1 H-imidazol-4-ylmethyl)-7phenyl- I H-I ,4-benzodiazepine, trihydrochioride; 2,3,4,5-Tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-7-phenyl-4-(3 -pyridinylcarbonyl)- IH- 1,4benzodiazepine, trihydrochioride; 4-[(2,6-Dimethoxy-3-pyridinyl)carbonyl]-2,3,4,5-tetrahydro- 1 I H-imidazol-4-ylmethyl)-7phenyl- I H-I ,4-benzodiazepine, trihydrochioride; 2,3 ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-7-phenyl-4-(2-pyrazinylcarbonyl)- 1 H- 1,4benzodiazepine, tetrahydrochioride; 4-(2-Ethoxybenzoyl)-2,3 ,4,5-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-7-phenyl- IH- 1,4benzodiazepine, dihydrochioride; 4-[3-(Dimethylamino)benzoyl]-2,3 ,4,5-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-7-phenyl- 1 H-i ,4-benzodiazepine, tri hydrochloride; 2,3 ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-7-phenyl-4-[( 1phenylcyclopropyl)carbonyl]- 1 H-i ,4-benzodiazepine, dihydrochioride; 4-[(Bicyclo[4.2.0]octa- 1,3 ,5-trien-7-yI)carbonyl]-2,3,4,5-tetrahydro- I H-imidazol-4- 00 ylinethyl)-7-phenyl- 1 H-i ,4-benzodiazepine, dihydrochioride; 4-Benzoyl-2,3,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-7-phenyl- 1 H- 1,4benzodiazepine, dihydrochioride; 4-(2-Chlorobenzoyl)-2,3,4,5-tetrahydro- 1-(1 H-imidazol-4-ylmethyl)-7-phenyl- I H- 1,4benzodiazepine, dihydrochioride; 4-(2,3-Dichlorobenzoyl)-2,3,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-7-phenyl- 1 H- 1,4- C) 10 benzodiazepine, di hydrochloride; ,4,5-Tetrahydro- 1-(1 H-imidazol-4-ylmethyl)-7-phenyl- 1H-i ,4-benzodiazepin-4yl]carbonyl]phenyl] -acetamide, dihydrochioride; 2,3 ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-4-(2-phenoxybenzoyl)-7-phenyl- 1 H- 1,4benzodiazepine, di hydrochloride; 2,3 ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-4-(2-methoxybenzoyl)-7-phenyl- 1 H- 1,4benzodiazepine, dihydrochioride; 4-(2,3-Dimethoxybenzoyl)-2,3 ,4,5-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-7-phenyl- 1H- I ,4-benzodiazepine, d ihydrochloride; 4-(2,4-Dimethoxybenzoyl)-2,3,4,5-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-7-phenyl- 1H- 1 ,4-benzodiazepine, d ihydrochloride; 4-(2,5-Dimethoxybenzoyl)-2,3,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-7-phenyl- 1 Hl- 1 ,4-benzodiazepine, dihydrochioride; 4-(2,6-Dimethoxybenzoyl)-2,3 ,4,5-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-7-phenyl- I H- 1 ,4-benzodiazepine, dihydrochioride; 4-(2,3-Dihydroxybenzoyl)-2,3 ,4,5-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-7-phenyl- 1H- 1 ,4-benzodiazepine, di hydrochioride; 1,1'-Biphenyl]-2-ylcarbonyl)-2,3 ,4,5-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-7-phenyl- 1 H-i ,4-benzodiazepine, di hydrochloride; 2,3 ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-4-(2-methylbenzoyl)-7-phenyl- 1 H- 1,4benzodiazepine, d ihydrochloride; 4-(2,3-Dimethylbenzoyl)-2,3 ,4,5-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-7-phenyl- 1H- 1,4benzodiazepine, dihydrochioride; 4-(3-Cyanobenzoyl)-2,3 ,4,5-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-7-phenyl- I H- 1,4benzodiazepine, dihydrochioride; 4-(3-Chlorobenzoyl)-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-7-phenyl- 1 H- 1,4benzodiazepine, dihydrochioride; o 2,3 ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-4-(3-phenoxybenzoyl)-7-phenyl- 1 H- 1,4- 00 benzodiazepine, dihydrochioride; 2,3 ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-4-(3-methoxybenzoyl)-7-phenyl-I1H- 1,4benzodiazepine, d ihydrochloride; 4-(3 ,4-Dimethoxybenzoyl)-2,3 ,4,5-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-7-phenyl- 1 H- 1 ,4-benzodiazepine, dihydrochioride; N4-(3,5-Dimethoxybenzoyl)-2,3,4,5-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-7-phenyl- 1H- C) 10 1 ,4-benzodiazepine, d ihydrochloride; N2,3,4,5-Tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-4-(3-methylbenzoyl)-7-phenyl- IH- 1,4benzodiazepine, dihydrochioride; 1,2-Dioxo-2-phenylethyl)-2,3 ,4,5-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-7-phenyl- 1 H- 1 ,4-benzodiazepine, dihydrochioride; 4-[2-Ethoxy- I -naphthalenyl)carbonyl]-2,3,4,5-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-7phenyl- 1 H-i ,4-benzodiazepine, dihydrochioride; 2,3 ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-4-(2-naphthalenylcarbonyl)-7-phenyl- 1 H- 1 ,4-benzodiazepine, di hydrochloride; 4-(Fluorophenylacetyl)-2,3,4,5-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-7-phenyl-I1H- 1,4zo benzodiazepine, dihydrochioride; 4-(Diphenylacetyl)-2,3 ,4,5-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-7-phenyl- I H- 1,4benzodiazepine, dihydrochioride; 2,3,4,5-Tetrahydro-4-(2-hydroxy- 1 -oxo-2-phenylpropyl)- 1 H-imidazol-4-ylmethyl)-7phenyl- 1 H-i ,4-benzodiazepine, dihydrochioride; 2,3 ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-4-( 1 H-indol-2-ylcarbonyl)-7-phenyl- 1 H- 1 ,4-benzodiazepine, di hydrochloride; 2,3 ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-4-( 1 H-indol-3-ylcarbonyl)-7-phenyl- 1 Hl- 1 ,4-benzodiazepine, dihydrochioride; 2,3,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-4-(1 H-indol-5-ylcarbonyl)-7-phenyl- 1 H- 1 ,4-benzodiazepine, dihydrochioride; 2,3 ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-4-[( 1-methyl- I H-indol-2-yl)carbonyl]-7phenyl- 1 H-i ,4-benzodiazepine, dihydrochioride; 4-(2-Benzofuranylcarbonyl)-2,3,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-7-phenyl- 1 H- 1 ,4-benzodiazepine, di hydrochloride; 43 2,3 ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-7-phenyl-4-(3-pyridinylcarbonyl)- 1 H- 1,4benzodiazepine, N-oxide, dihydrochioride; o 2,3 ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-7-phenyl-4-(2-pyridinylcarbonyl)- 1 H- 1,4- 00 benzodiazepine, tri hydrochloride; 2,3 ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-7-phenyl-4-(2-quinolinylcarbonyl)- I H- 1,4benzodiazepine, tri hydrochloride; 2,3 ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-7-phenyl-4-( 1 -isoquinolinylcarbonyl)- I H- 1 ,4-benzodiazepine, tri hydrochloride; 4-(3-Chloro-2-nitrobenzoyl)-2,3 ,4,5-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-7-phenyl- 1H- 1 ,4-benzodiazepine, dihydrochioride; 2,3 ,4,5-Tetrahydro- I H-imidazol-4-ylmethyl)-4-(2-nitrobenzoyl)-7-pheryl- I H- 1,4benzodiazepine, d ihydrochloride; 2,3,4,5-Tetrahydro-1I H-imidazol-4-ylmethyl)-4-(3-methoxy-2-nitrobenzoyl)-7-phenyl- 1 H-i ,4-benzodiazepine, dihydrochioride; 2,3 ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-4-( I H-indol-4-ylcarbonyl)-7-phenyl- 1 H- 1 ,4-benzodiazepine, d ihydrochloride; 4-[(2,6-Dihydroxy-3 -naphthalenyl)carbonyl] -2,3,4,5 -tetrahydro- 1-(1 H-imidazol-4ylmethyl)-7-phenyl- 1 H-I ,4-benzodiazepine, dihydrochioride; 1H-Benzimidazol-5-ylcarbonyl)-2,3 ,4,5-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-7phenyl-1I H- 1,4-benzodiazepine, trihydrochioride; 1H-Benzotriazol-5-ylcarbonyl)-2,3,4,5-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-7-phenyl- 1 H-i ,4-benzodiazepine, di hydrochloride; 2,3 ,4,5-Tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-4-[(4-methoxy-2-quinolinyl)carbonyl]-7phenyl- 1 H-i ,4-benzodiazepine, trihydrochioride; ,4,5-Tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-7-phenyl- 1H-i ,4-benzodiazepin-4yl] carbonyl]phenyl]-acetamide, d ihydrochloride; 2,3 ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-4-(2-methyl- 1 -oxo-2-phenylpropyl)-7phenyl-1I H-i ,4-benzodiazepine, dihydrochioride; imethy lam ino)benzoyl -tetrahydro- 1 H-imidazol-4-ylmethyl)-7-phenyl- 1 H-i ,4-benzodiazepine, trihydrochioride; 4-(3-Ethoxybenzoyl)-2,3,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-7-phenyl- 1 H- 1,4benzodiazepine, di hydrochloride; 2,3,4,5-Tetrahydro-4-(2-hydroxy[ 1,1 '-biphenyl]-3-ylcarbonyl)- 1-(1 H-imidazol-4ylmethyl)-7-phenyl- 1 H-i ,4-benzodiazepine, dihydrochioride; 2,3 ,4,5-Tetrahydro-4- [2-[(2-hydroxyethyl)thio]benzoyl]- I H-imidazol-4-ylmethyl)-7phenyl- I H-I ,4-benzodiazepine, dihydrochioride; o 2,3,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-4-[(2-methoxy- I -naphthalenyl)carbonyl]-7- 00 phenyl- 1 H-i ,4-benzodiazepine, dihydrochioride; 2,3,4,5-Tetrahydro-4-[(2-hydroxy-4-quinolinyl)-carbonyl]- 1 H-imidazol-4-ylmethyl)-7phenyl- I H-I ,4-benzodiazepine, dihydrochioride; ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-7-phenyl- 1 H-I ,4-benzodiazepin-4yl]carbonyl]benzamide, dihydrochioride; IDN-( 1,1-Dimethylethyl)-2-[[2,3 ,4,5-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-7-phenyl- IH- 1 ,4-benzodiazepin-4-yl] carbonyl]benzamide, dihydrochioride; N-(4-Fluorophenyl)-N'-[3-[[2,3 ,4,5-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-7-phenyl- IH- 1 ,4-benzodiazepin-4-yI]carbonyl]phenyl] urea, dihydrochioride; 2,3,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-4-[(3-methyl-4-oxo-2-phenyl-4Hbenzopyran-8-yl)carbonyl]-7-phenyl- 1H-I ,4-benzodiazepine, dihydrochioride; 2,3,4,5-Tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-7-phenyl-4-[3-(trifluoromethoxy)benzoyl]- 1 H-i ,4-benzodiazepine, dihydrochioride; 4-(2-Cyanobenzoyl)-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-7-phenyl- I H- 1,4benzodiazepine, di hydrochloride; 2,3,4,5-Tetrahydro- 1 I H-imidazol-4-ylmethyl)-4-[2-[[(4methyl phenylI)sul fonylI]amino] benzoyl] -7-phenyl- 1 H-I ,4-benzodiazepine, d ihydrochloride; 2,3,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-7-phenyl-4-(6-quinolinylcarbonyl)- I H- 1,4benzodiazepine, trihydrochioride; 2,3,4,5-Tetrahydro-l1-( IH-imidazol-4-ylmethyl)-7-phenyl-4-(8-quinolinylcarbonyl)- 1H- 1,4benzodiazepine, tri hydrochioride; 4-(Benzo[b]thiophen-2-ylcarbonyl)-2,3,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-7phenyl- 1 H-i ,4-benzodiazepine, dihydrochioride; 4-[[4-(Dimethylamino)- 1 -naphthalenyl]carbonyl]-2,3 ,4,5-tetrahydro- 1 H-imidazol-4ylmethyl)-7-phenyl- 1 H-i ,4-benzodiazepine, trihydrochioride; 2,3,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-7-phenyl-4-( 1 H-purin-6-ylcarbonyl)- I Hl- 1 ,4-benzodiazepine, trihydrochioride; 2,3,4,5-Tetrahydro- 1-(1 H-imidazol-4-ylmethyl)-4-(methoxyphenylacetyl)-7-phenyl- 1H- 1,4benzodiazepine, di hydrochloride; 2,3,4,5-Tetrahydro- I I H-imidazol-4-ylmethyl)-4-[(5-methyl- 1 -phenyl- I H-pyrazol-4yl)carbonyl]-7-phenyl-1I H-i ,4-benzodiazepine, trihydrochioride; 2,3 ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-4-[2-(2-methylphenyl)- 1 -oxopropyl]-7phenyl- 1 H-i ,4-benzodiazepine, dihydrochioride; o 2,3,4,5 -Tetrahydro- 1 H-imidazol-4-ylmethyl)-7-phenyl-4- [(tetrahydro-4-phenyl-2H- 00 pyran-4-yl)carbonyl]- I H-i ,4-benzodiazepine, dihydrochioride; 2,3 ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-4-[2-(methylphenylamino)benzoyl]-7phenyl- 1 H-I ,4-benzodiazepine, trihydrochioride; 2,3 ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-7-phenyl-4-(4-quinolinylcarbonyl)- 1 H- 1,4benzodiazepine, N-oxide, dihydrochioride; IND N-Methyl-N-(2-pyridinylmethyl)-2-[[2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-7- C) 10 phenyl- 1 H-i ,4-benzodiazepin-4-yI]carbonyl]benzamide, trihydrochioride; 2,3 ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-4-(3-isoquinolinylcarbonyl)-7-phenyl- 1 H- 1 ,4-benzodiazepine, trihydrochioride; 2,3,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-4-[(2-naphthalenylthio)acetyl]- 1 H- 1,4benzodiazepine, trifluoroacetate ,4-Dimethoxyphenyl)- I -oxopropyl]-2,3 ,4,5-tetrahydro- I H-imidazol-4-ylmethyl)- I H-i ,4-benzodiazepine, trifluoroacetate 1,1 '-Biphenyl]-4-ylacetyl)-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)- I H- 1,4benzodiazepine, trifluoroacetate 2,3 ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-4-(2-naphthalenylacetyl)- I H- 1,4benzodiazepine, trifluoroacetate 1,1 '-Biphenyl]-2-ylcarbonyl)-2,3,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)- I H- 1,4benzodiazepine, trifluoroacetate 2,3 ,4,5-Tetrahydro- I H-imidazol-4-ylmethyl)-4-[(2-phenyl4-quinolinyl)carbonyl]- 1 H- 1 ,4-benzodiazepine, trifluoroacetate 2,3 ,4,5-Tetrahydro- I H-imidazol-4-ylmethyl)-4-(3-pyridinylacetyl)- 1 H- 1,4benzodiazepine, trifluoroacetate 4-(9H-Fluoren-9-ylacetyl)-2,3,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)- I H- 1,4benzodiazepine, trifluoroacetate [2-(Di methylIamino)- 1 -oxo-3-phenylpropyl]-2,3 ,4,5-tetrahydro- 1 H-imidazol-4ylmethyl)- 1 H-i ,4-benzodiazepine, trifluoroacetate ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-4-[(2-oxo-4-phenyl-3oxazolidinyl)acetyl]- 1 H-i ,4-benzodiazepine, trifluoroacetate 4-(9-Acridinylcarbonyl)-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)- 1 H- 1,4benzodiazepine, trifluoroacetate 2,3,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-4-(3-phenoxybenzoyl)- I H- 1,4benzodiazepine, trifluoroacetate o ~2,3 ,4,5-Tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-4-[[4'-(trifluoromethyl)[ 1,1 '-biphenyl]-2- 00 yl]carbonyl]- 1H-i ,4-benzodiazepine, trifluoroacetate 2,3 ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-4-(4-phenoxybenzoyl)- 1 H- 1,4benzodiazepine, trifluoroacetate C 2,3 ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-4-(2-naphthalenylcarbonyl)- I H- 1,4benzodiazepine, trifluoroacetate IND2,3 ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-4-( 1 -oxo-4-phenylbutyl)- I H- 1,4benzodiazepine, trifluoroacetate 2,3 ,4,5-Tetrahydro- I H-imidazol-4-ylmethyl)-4-[(2-phenoxyphenyl)acetyl]- 1 Hl- 1,4benzodiazepine, trifluoroacetate 2,3 ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-4-[2-[(4-methylphenyl)sulfinyl]benzoyl]- I H-i ,4-benzodiazepine, trifluoroacetate 2,3 ,4,5-Tetrahydro- I H-imidazol-4-ylmethyl)-4-[2-[(phenylmethyl)amino]benzoyl]- I H- 1 ,4-benzodiazepine, trifluoroacetate 1,2,3 ,5-Tetrahydro- 1 H-imidazol-4-yl-methyl)-N,N-diphenyl-4H- 1 ,4-benzodiazepine-4carboxamide, hydrochloride; 1,2,3 ,5-Tetrahydro- 1 H-imidazol-4-yl-methyl)-a,7-diphenyl-4H- 1 ,4-benzodiazepine-4acetic acid, methyl ester, hydrochloride; 4-Acetyl-2,3,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-3-(phenylmethyl)- 1 H- 1,4benzodiazepine, hydrochloride; (R)-7-Bromo-2,3 ,4,5-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-4-(methylsulfonyl)-3 (phenylmethyl)- 1 H-i ,4-benzodiazepine, hydrochloride; ,4,5-Tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-4-(methylsulfonyl)-3-(phenylmethyl)- 1 H-I ,4-benzodi azepi ne-7 -carbon itri le, monohydrochloride; (R)-4-Acetyl-2,3 ,4,5-tetrahydro-lI-( IH-imidazol-4-ylmethyl)-7-phenyl-3 -(phenylmethyl)- 1 H-i ,4-benzodiazepine, monohydrochloride; 7-Bromo-4-[[2-(dimethylamino)ethyl]sulfonyl]-2,3 ,4,5-tetrahydro- 1 H-imidazol-4ylmethyl)-3-(phenylmethyl)-4H- 1,4-benzodiazepine, trifluoroacetate 2,3,4,5-Tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-7-phenyl-4-[( 1,2,3 ,4-tetrahydro- 1quinolinyl)carbonyl]- 1 H-i ,4-benzodiazepine, monohydrochloride; N-Ethyl- 1,2,3 ,5-tetrahydro- 1-(1 H-imidazol-4-ylmethyl)-N,7-diphenyl-4H- 1,4benzodiazepine-4-carboxamide, monohydrochloride; 4-[(2,3-Dihydro- 1 H-indol- 1 -yI)carbonyl]-2,3,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-7phenyl- I Hl-i ,4-benzodiazepine, monohydrochioride; o 2,3,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-4-(methylsulfonyl)-3-(phenylmethyl)-7-(4- 00 pyridinyl)- I H-i ,4-benzodiazepine, trihydrochioride; (R)-4-[[2-(Dimethylamino)ethyl]sulfonyl]-2,3,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)- 7-phenyl-3-(phenylmethyl)- I H-i ,4-benzodiazepine, trifluoroacetate 1); [2,3 ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-4-( I -naphthalenylcarbonyl)- 1 H- 1,4benzodiazepin-8-yl]carbamic acid, cyclohexyl ester, dihydrochioride; IND (R)-7-Bromo-2,3 ,4,5-tetrahydro- 1 -(I1-methyl- I H-imidazol-5-yl)methyl)-4-(methylsulfonyl)- 3-(phenylmethyl)- 1 H-i ,4-benzodiazepine, hydrochloride; (R)-7-Cyano-2,3 ,4,5-tetrahydro- I -+(1-methyl- I H-imidazol-5-yl)methyl]-4- (methylsulfonyl)-3 -(phenylmethyl)- 1 H-i ,4-benzodiazepine, monohydrochloride; 4-[2-(4-Chlorophenyl)- 1 ,2-dioxoethyl]-2,3,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-7phenyl-1I H-I ,4-benzodiazepine, hydrochloride; 4-(1I,2-Dioxopropyl)-2,3 ,4,5-tetrahydro- I H-imidazol-4-ylmethyl)-7-phenyl- 1 H- 1,4benzodiazepine, hydrochloride; 2,3,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-4-[2-(4-nitrophenyl)- 1 ,2-dioxoethyl]-7phenyl- 1 H-I ,4-benzodiazepine, hydrochloride; 2,3 ,4,5-Tetrahydro- I H-imidazol-4-ylmethyl)-4-[2-(4-methoxyphenyl)- 1 ,2-dioxoethyl]-7phenyl-1I H-I ,4-benzodiazepine, hydrochloride; 2,3 ,4,5-Tetrahydro- I H-imidazol-4-ylmethyl)-7-phenyl-4-(3 ,3,3 -trifluoro- 1,2dioxopropyl)- 1 H-i ,4-benzodiazepine, trifluoroacetate (R)-7-Bromo-2,3 ,4,5-tetrahydro- I H-imidazol-4-ylacetyl)-4-(methylsulfonyl)-3- (phenylmethyl)- 1 H-i ,4-benzodiazepine, monohydrochloride; (R)-7-Bromo-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylethyi)-4-(methylsulfonyl)-3- (phenylmethyl)- 1 Hl-i ,4-benzodiazepine, monohydrochioride; 8-[(Cyclohexylcarbonyl)amino]- 1,2,3 ,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-3- (phenylmethyl)-4H-1I,4-benzodiazepine-4-carboxyl ic acid, methyl ester, dihydrochioride; N-[2,3 ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-4-( 1 -naphthalenylcarbonyl)- 1 H- 1,4benzodiazepin-8-yl- I -piperidinecarboxamide, dihydrochloride; (R)-7-Cyano- 1,2,3 ,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-3-(phenylmethyl)-4H- 1,4benzodiazepine-4-carboxyi ic acid, ethyl ester, hydrochloride; N-[2,3 ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-4-(methylsulfonyl)-3 -(phenylmethyl)- 1 H-I ,4-benzodiazepin-8-yllcyclohexanecarboxamide, dihydrochloride; (R)-7-Cyano-4-[[2-(dimethylamino)ethyl]sulfonyl]-2,3 ,4,5-tetrahydro- 1 H-imidazol-4ylmethyl)-3-(phenylmethyl)-4H- 1,4-benzodiazepine, di hydrochloride; o (R)-7-Cyano-2,3,4,5-tetrahydro-1I -(I1H-imidazol-4-ylmethyl)-4-[[2-(4- 00 morpholinyl)ethyl]sulfonyl]-3-(phenylmethyl)-4H- 1,4-benzodiazepine, d ihydrochloride; N-[2,3 ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-4-(2-methoxy-3-methylbenzoyl)- 1 H- 1 ,4-benzodiazepin-8-yl] cyclohexanecarboxamide, dihydrochioride, 8-[(Cyclohexylcarbonyi)amino]-2,3,4,5-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-N-phenyl- 1 H-i ,4-benzodiazepine-4-carboxamide, dihydrochioride; N-[2,3 ,4,5-Tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-4-[(2-methylphenyl)sulfonyl]-I1H- 1,4- C) 10 benzodiazepin-8-yl]cyclohexanamide, dihydrochioride; N-[2,3,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-4-[(2-methoxyphenyl)carbonyl]- 1 Hl- 1 ,4-benzodiazepin-8-yl]cyclohexanamide, dihydrochioride; (R)-7-Cyano- 1,2,3 ,5-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-3-(phenylmethyl)-4H- 1,4benzodiazepine-4-sulfonic acid, ethyl ester, hydrochloride; (3R)-7-Bromo-l1-[cyano( 1H-imidazol-4-yl)methyl]-2,3 ,4,5-tetrahydro-4-(methylsulfonyl)-3 (phenylmethyl)- I Hl-i ,4-benzodiazepine, monohydrochloride; (3 1-[2-Amino-I H-imidazol-4-yl)ethyl]-2,3,4,5-tetrahydro-4-(methylsulfonyl)-3 (phenylmethyl)- 1 H-i ,4-benzodiazepine, dihydrochloride; 1-[2-(Dimethylamino)- 1-(1 H-imidazol-4-yl)ethyl]-2,3 ,4,5-tetrahydro-4- 20(methylsulfonyl)-3-(phenylmethyl)- IH-i ,4-benzodiazepine, dihydrochloride; 1 -[2-Amino- I H-imidazol-4-yl)ethyl]-7-bromo-2,3,4,5-tetrahydro-4- (methylsulfonyl)-3-(phenylmethyl)- I H-i ,4-benzodiazepine, dihydrochioride; 1 -[2-(Dimethylamino)- 1 H-imidazol-4-yl)ethyl]-7-bromo-2,3 ,4,5-tetrahydro-4- (methylsulfonyl)-3-(phenylmethyl)- 1H-I ,4-benzodiazepine, di hydrochloride; 7-Cyano- 1,3,4,5-tetrahydro-lI-(1-methyl-i H-imidazol-5-ylmethyl)-3-(phenylmethyi)-4- (phenylsulfonyl)-2H- 1,4-benzodiazepin-2-one, monohydrochloride; 7-Cyano- 1,3 ,4,5-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-3-(phenylmethyl)-4- (phenylsulfonyl)-2H- 1,4-benzodiazepin-2-one, monohydrochloride; 7-Bromo-2,3 ,4,5-tetrahydro-l1-( IH-imidazoi-4-ylmethyi)-4-(methylsulfonyl)-3 phenylethyl)- I H-i ,4-benzodiazepine, dihydrochloride; 7-Bromo-3 -[(3-chlorophenyl)methyl]-2,3 ,4,5-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-4- (methylsulfonyl)-l1H-I ,4-benzodiazepine, dihydrochloride; (R)-7-Bromo-3-(cyclohexylmethyl)-2,3 ,4,5-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-4- (methylsulfonyl)- 1 H-I ,4-benzodiazepine, dihydrochloride; 7-Bromo-3-[(2-chlorophenyl)methyl]-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-4- (methylsulfonyl)- 1 H-I ,4-benzodiazepine, di hydrochloride; o (S)-7-Bromo-3-(cyclohexyimethyl)-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-4- 00 (methylsulfonyl)- 1 H-i ,4-benzodiazepine, dihydrochioride; 7-Bromo-2,3,4,5-tetrahydro- 1 H-imidazol-4-yimethyl)-3 -[(4-methoxyphenyl)methyl]-4- (methylsulfonyl)- 1 H-I ,4-benzodiazepine, dihydrochioride; 4-Acetyl-7-bromo-3-[(2-chlorophenyl)methyl]-2,3,4,5-tetrahydro- 1 H-imidazol-4ylmethyl)- I H-i ,4-benzodiazepine, dihydrochioride; IND 4-Acetyl-7-bromo-3-[(3-chlorophenyl)methyl]-2,3 ,4,5-tetrahydro- 1 H-imidazol-4ylmethyl)- I Hl-I ,4-benzodiazepine, di hydrochloride; 7-Bromo-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-3 -[(4-hydroxyphenyl)methyl]-4- (methylsulfonyl)- I H-i ,4-benzodiazepine, dihydrochioride; (R)-2,3,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-4-(methylsulfonyl)-7-phenyl-3 pyridinylmethyl)- 1 H-I ,4-benzodiazepine, dihydrochioride; 2,3,4,5-Tetrahydro-8-(hydroxymethyl)- 1 H-imidazol-4-ylmethyl)-4-( 1naphthalenylcarbonyl)- 1 H-i ,4-benzodiazepine, di hydrochloride; 2,3 ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-4-( I -naphthalenylcarbonyl)-8- (phenoxymethyl)- IH-i ,4-benzodiazepine, dihydrochioride; N-Cyclohexyl-2,3,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-4-( 1 -naphthalenylcarbonyl)- 0 1 H-I ,4-benzodiazepine-8-carboxamide, dihydrochioride; N-(Cyclohexylmethyl)-2,3,4,5-tetrahydro- I H-imidazol-4-ylmethyl)-4-( 1naphthalenylcarbonyl)- 1 H-i ,4-benzodiazepine-8-carboxamide, dihydrochioride; 2,3 ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-4-( 1 -naphthalenylcarbonyl)-N- (phenylmethyl)- 1 H-i ,4-benzodiazepine-8-carboxamide, dihydrochioride; (R)-4-Acetyl-7-[2-[(dimethylamino)methyl]phenyl]-2,3,4,5-tetrahydro- 1 H-imidazol-4ylmethyl)-3 -(phenylmethyl)- 1 H-I ,4-benzodiazepine, dihydrochioride; (R)-4-Acetyl-7-cyano-2,3 ,4,5-tetrahydro- 1 I H-imidazol-4-ylmethyl)-3-(phenylmethyl)- 1 H-I ,4-benzodiazepine, monohydrochioride; (R)-7-Cyano-2,3 ,4,5-tetrahydro- 1 I H-imidazol-4-ylmethyl)-4-( 1 -oxobutyl)-3- (phenylmethyl)- 1 H-I ,4-benzodiazepine, monohydrochioride; (R)-7-Cyano-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-4-(2-methyl- 1 -oxopropyl)-3- (phenylmethyl)- 1 H-I ,4-benzodiazepine, monohydrochioride; (R)-7-Cyano-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-3 -(phenylmethyl)-4-(2pyridinylacetyl)- 1 H-I ,4-benzodiazepine, dihydrochioride; (R)-7-Cyano-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-3 -(phenylmethyl)-4-(2thienylsulfonyl)- 1 H-i ,4-benzodiazepine, monohydrochioride; o (R)-7-Cyano-2,3 ,4,5-tetrahydro- I H-imidazol-4-ylmethyl)-4-[( 1 -methylethyl)sulfonyl]-3- 00 (phenylmethyl)- 1 Hl-i ,4-benzodiazepine, monohydrochioride; (R)-7-Cyano-2,3 ,4,5-tetrahydro- 1 H-imidazoi-4-ylmethyl)-3 -(phenylmethyl)-4- [(trifluoromethyl)sulfonyl]- 1H-i ,4-benzodiazepine, monohydrochioride; (R)-7-Bromo-2,3,4,5-tetrahydro-l1-(1 H-imidazol-4-yimethyi)-3-(phenylmethyl)-4- (propylsulfonyl)- 1 H-i ,4-benzodiazepine, monohydrochioride; (R)-7-Bromo-2,3,4,5-tetrahydro-1 -(1H-imidazol-4-ylmethyl)-3-(phenylmethyl)-4- C) 10 (phenylsulfonyl)-l1H-i ,4-benzodiazepine, monohydrochioride;

(N

,4,5-Tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-7-phenyl-3-(phenylmethyl)-4- (phenylsul fonyl)- 1 Hl-i ,4-benzodiazepine, monohydrochioride; ,4,5-Tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-7-phenyl-3-(phenylmethyl)-4- (propyisulfonyl)- I H-i ,4-benzodiazepine, monohydrochioride; (R)-7-Cyano-4-[(4-fluorophenyl)sulfonyl]-2,3,4,5-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)- 3 -(phenylmethyl)- I H-i ,4-benzodiazepine, monohydrochioride; (R)-7-Cyano-4-[(3-cyanophenyl)sulfonyl]-2,3,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)- 3 -(phenylmethyl)- I Hl-I ,4-benzodiazepine, monohydrochioride; (R)-7-Cyano-2,3 ,4,5 -tetrahydro- 1 I H-imidazol-4-ylmethyl)-4- 1-methyl -I H-imidazol-2yl)sulfonyl]-3-(phenylmethyl)- 1H-i ,4-benzodiazepine, di hydrochloride; (R)-4-[(3-Bromophenyl)sulfonyl]-7-cyano-2,3,4,5-tetrahydro- I H-imidazol-4-ylmethyl)- 3 -(phenylmethyl)- 1H-i ,4-benzodiazepine, monohydrochioride; (R)-N-[5-[[7-cyano-2,3,4,5-tetrahydro-l1-( IH-imidazoi-4-ylmethyl)-3 -(phenylmethyl)- 1H- I ,4-benzodiazepin-4-yl] sul fonyl] -4-methyl-2-thiazoiyi]acetamide, dihydrochioride; 4-Acetyl-2,3 ,4,5 -tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-3-(phenylmethyl)-7-(4-pyridinyl)- 1 H-i ,4-benzodiazepine, trihydrochioride; 2,3 ,4,5-Tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-4-(2-phenyl- 1,2-dioxoethyl)-7-(4pyridinyl)- I H-I ,4-benzodiazepine, trihydrochioride; 2,3,4,5-Tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-7-(4-pyridinyl)-4-[2- (trifluoromethoxy)benzolyl]- 1 H-i ,4-benzodiazepine, trihydrochioride; ,4,5-Tetrahydro-lI-[(i-methyl-I H-imidazol-5-yl)methyl]-4-(methylsulfonyl)-7phenyl-3 -(phenylmethyl)- 1H-i ,4-benzodiazepine; (R)-7-Cyano-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyi)-4-(phenylacetyl)-3- (phenylmethyl)- I H-i ,4-benzodiazepine, monohydrochioride; 4-(2-Benzothiazolyl)-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-7-phenyl- 1 H- 1,4benzazepine, trihydrochioride;

C.)

00 (trifluoroacetyl)- I H-I ,4-benzodiazepine, trihydrochioride; 2,3 ,4,5-Tetrahydro- 1 H-imidazol-4-yimethyl)-4-(methylsulfonyl)-3-(phenylmethyl)-7-(3pyridinyl)- 1 Hl-i ,4-benzodiazepine, trihydrochioride; 7-Bromo-3-[(1,1I -dimethylethoxy)methyi]- 1 ,2,3,4-tetrahydro- 1 H-imidazol-4-yimethyl)- ,4-benzod iazepi n-5 -one; IND7-Bromo-2,3 ,4,5-tetrahydro- 1 H-imidazoi-4-ylmethyl)-4-(methylsulfonyl)-3 C) 10 (phenoxymethyl)- I H-i ,4-benzodiazepine, dihydrochioride; 7-Bromo-2,3 ,4,5-tetrahydro-3-(hydroxymethyl)- 1 H-imidazol-4-yimethyl)-4- (methylsulfonyl)- 1 H-i ,4-benzodiazepine, monohydrochioride; 7-Bromo-3 -dimethyiethoxy)methyl]-2,3,4,5-tetrahydro- I H-imidazol-4-ylmethyl)- 4-(methylsulfonyl)- 1 H-i ,4-benzodiazepine; [7-Bromo-2,3 ,4,5-tetrahydro- I H-imidazol-4-ylmethyl)-3 -(phenylmethyl)- I H- 1,4benzodiazepin-8-yI]carbamic acid, 2-methyipropyl ester, tri hydrochloride; [4-Acetyl-7-bromo-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-3-(phenylmethyl)- 1 Hl- 1 ,4-benzodiazepin-8-yI]carbamic acid, 2-methyipropyl ester; N-[4-Acetyl-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-3-(phenylmethyl)- I H- 1,4benzodiazepin-8-yl]cyclohexanecarboxamide, dihydrochioride; [7-Bromo-2,3 ,4,5-tetrahydro-l1-(1 H-imidazol-4-ylmethyi)-4-(methylsulfonyl)-3- (phenylmethyl)-i H-i ,4-benzodiazepin-8-yl]carbamic acid, 2-methyipropyl ester; ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-4-(phenylsulfonyl)-3-(phenylmethyl)- 1 H-i ,4-benzodiazepine-7-carbonitrile, monohydrochioride; 7-Bromo- 1,2,3 ,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-3 -(phenylmethyl)-4H- 1,4benzodiazepine-4-acetamide; 7-Bromo-4-[(dimethylamino)acetyl]-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-3- (phenylmethyl)- I Hl-i ,4-benzodiazepine; (R)-7-iBromo-4-(1I,2-dioxopropyl)-2,3,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-3- (phenylmethyl)- 1 H-i ,4-benzodiazepine, trifluoroacetate; (R)-7-Bromo-4-(cyclopropylcarboonyl)-2,3 ,4,5-tetrahydro- I H-imidazol-4-ylmethyl)-3- (phenylmethyl)- 1 H-I ,4-benzodiazepine, trifluoroacetate; (R)-7-Cyano-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-3 -(phenylmethyl)-4- (propyisulfonyl)- 1 H-i ,4-benzodiazepine, monohydrochioride; 7-Bromo-2,3 ,4,5-tetrahydro- I ,4-bis( I H-imidazol-4-ylmethyl)-3 -(phenylmethyl)- 1 H- 1,4benzodiazepine, dihydrochioride; o ~7-Bromo- 1,2,3,5-tetrahydro- 1-(1 H-imidazol-4-yimethyl)-N,N-dimethyl-3-(phenylmethyl)- 00 4H- 1,4-benzodiazepine-4-sulfonamide, monohydrochioride; 2,3 ,4,5-Tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-4-(methyisulfonyl)-3-(phenylmethyl)- 1H- 1 ,4-benzodiazepine-7-carbonitrile, monohydrochioride; (R)-7-Cyano- 1,2,3 ,5-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-N,N-dimethyl-3- (phenylmethyl)-4H- 1,4-benzodiazepine-4-carboxamide, monohydrochioride; N,N-Diethyl-2,3 ,4,5-tetrahydro- 1-(1 H-imidazol-4-ylmethyl)-4-(methylsulfonyl)-3 C) 10 (phenylmethyl)- I H-I ,4-benzodiazepine-7-carboxamide, monohydrochioride; 2,3 ,4,5-Tetrahydro- 1-(1 H-imidazol-4-ylmethyl)-7-phenyl-4-(1I-phenyl- 1 H-i ,4-benzodiazepine, monohydrochioride; (R)-7-Cyano-2,3 ,4,5-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-3 -(phenylmethyl)-4-(2pyrazinylcarbonyl)-4H-1I,4-benzodiazepine, monohydrochioride; (R)-4-[7-Bromo-2,3,4,5-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-3-(phenylmethyl)-4H- 1,4benzodiazepin-4-yl]-4-oxobutanoic acid, methyl ester, monohydrochioride; (R)-7-Cyano-2,3 ,4,5-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-4-(4-morpholinylcarbonyl)-3 (phenylmethyl)- 1 H-i ,4-benzodiazepine, monohydrochioride; (R)-7-Cyano-2,3,4,5-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-3 -(phenylmethyl)-4-[[2-( Ipyrrolidinyl)ethyl]sulfonyl]- I H-i ,4-benzodiazepine, dihydrochioride; ,4,5-Tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-4-(methylsulfonyl)-7-phenyl-3 pyridinylmethyl)- 1 H-I ,4-benzodiazepine, dihydrochioride; ,4,5-Tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-7-phenyl-3-(3-pyridinylmethyl)-4-(2thienylsulfonyl)- I H-I ,4-benzodiazepine, dihydrochioride; ,4,5-Tetrahydro- 1-(1 H-imidazol-4-ylmethyl)-7-phenyl-4-(propysulfonyl)-3 pyridinylmethyl)- 1 H-i ,4-benzodiazepine, monohydrochioride; (R)-7-Bromo-2,3 ,4,5-tetrahydro- 1 (1 H-imidazol-4-ylmethyl)-4-(methylsulfonyl)-3 pyridinylmethyl)- 1 H-i ,4-benzodiazepine, monohydrochioride; 2,3 ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-4-(methylsulfonyl)-3-(phenylmethyl)-7-(2pyrimidinyl)-1I H-I ,4-benzodiazepine, dihydrochioride; (R)-7-Bromo-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-3 -(phenylmethyl)-4- [(trifluoromethyl)sulfonyl]- 1 H-i ,4-benzodiazepine, monohydrochioride; (R)-2,3,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-7-phenyl-3-(phenylmethyl)-4- (trifluoroacetyl)- 1 H-I ,4-benzodiazepine, monohydrochioride; ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-4-(methylsulfonyl)-3 -(phenylmethyl)- 7-(4-pyridinyl)- I H-I ,4-benzodiazepine, dihydrochioride;

C.)

00 thienylsulfonyl)- I H-i ,4-benzodiazepine, dihydrochioride; ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-3-(phenylmethyl)-4-(phenylsulfonyl)- 7-(4-pyridinyl)-l1H-I ,4-benzodiazepine, dihydrochioride; ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-3-(phenylmethyl)-4-(propylsulfonyl)-7- (4-pyridinyl)- 1 H-I ,4-benzodiazepine, dihydrochioride; IND(R)-7-Cyano-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-3 -(phenylmethyl)-4-[(3 C) 10 dimethyl-isoxazol-4-yl)sulfonyl]- 1 H-i ,4-benzodiazepine, di hydrochloride; (R)-7-Cyano-4-[(4-cyanophenyl)sulfonyl]-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)- 3 -(phenylmethyl)- 1H-i ,4-benzodiazepine, dihydrochioride; (R)-7-Cyano-2,3 ,4,5-tetrahydro-l1-( IH-imidazol-4-ylmethyl)-3 -(phenylmethyl)-4-[(2,2,2trifluoroethyl)sulfonyl] -1H-i ,4-benzodiazepine, dihydrochioride; (R)-[(5-Bromo-2-thienyl)sulfonyl]-7-cyano-2,3 ,4,5-tetrahydro- 1 I H-imidazol-4-ylmethyl)- 3-(phenylmethyl)- 1 H-i ,4-benzodiazepine, dihydrochioride; (R)-7-Cyano-2,3,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-4-[(4methoxyphenyl)sulfonyl] -3-(phenylmethyl)- 1H-I ,4-benzodiazepine, di hydrochloride; N-[[7-Bromo-2,3 ,4,5-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-4-(methylsulfonyl)-l1H- 1,4benzodiazepin-3 -yl] methyl]benzamide, dihydrochioride; (R)-7-Cyano-1I,2,3,5-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-N,N-dimethyl-3- (phenylmethyl)-4H- 1,4-benzodiazepine-4-sulfonamide, hydrochloride; (R)-7-Cyano- 1,2,3 ,5-tetrahydro-N,N-dimethyl-l1-[(1-methyl-i H-imidazol-5-yl)methyl]-3- (phenylmethyl)-4H- 1,4-benzodiazepine-4-sulfonamide, hydrochloride; (R)-7-Chloro-2,3 ,4,5-tetrahydro- 1 I-methyl- I H-imidazol-5-yl)methyl]-4- (methylsulfonyl)-3-(phenylmethyl)-I H-i ,4-benzodiazepine, monohydrochloride; (R)-7-Chloro-2,3 ,4,5-tetrahydro- 1-(1 H-imidazol-4-ylmethyl)-4-(methylsulfonyl)-3 (phenylmethyl)- 1 H-i ,4-benzodiazepine, monohydrochloride; (R)-7-Chloro-2,3 ,4,5-tetrahydro-l1-[(1-methyl-I H-imidazol-5-yl)methyl]-4- (phenylsulfonyl)-3 -(phenylmethyl)- 1 H-I ,4-benzodiazepine, monohydrochloride; (R)-7-Cyano-2,3 ,4,5-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-3 -(pyridin-3 -ylmethyl)-4- (methylsulfonyl)- 1 H-i ,4-benzodiazepine, tetrahydrochloride; (R)-7-Bromo-2,3 ,4,5-tetrahydro- 1 H-imidazol-2-ylmethyl)-4-(methylsulfonyl)-3- (phenylmethyl)- 1 Hl-I ,4-benzodiazepine, di hydrochloride; (R)-7-Bromo-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-yimethyl)-4-[( 1-methyl- I H-imidazol-4yl)sulfonyi]-3-(phenylmethyl)- 1H-i ,4-benzodiazepine, trihydrochioride; o (R)-7-Chloro-2,3 ,4,5-tetrahydro-l1-(1 -methyl-imidazol-5-ylmethyl)-4-[(2-morphoiin-4-yl- 00 ethyl)sulfonyl] -3 -(phenylmethyl)- IH-i ,4-benzodiazepine, dihydrochioride; (R)-7-Chloro-2,3 ,4,5-tetrahydro- 1-(1 H-imidazol-4-ylmethyl)-4-[(2-morpholin-4-ylethyl)sulfonyl]-3-(phenyimethyl)- IH-i ,4-benzodiazepine, dihydrochloride; (R)-7-Chloro-4-[(dimethylamino)sulfonyl]- I-[(i-methyl-i H-imidazol-5-yl)methyl]-3- (phenylmethyl)- I H-i ,4-benzodiazepine, monohydrochioride; (R)-7-Chloro-2,3,4,5-tetrahydro- 1 I -methyl-imidazoi-5-ylmethyl)-4-[(4-methyl-piperidin- C) 10 4-yl-ethyl)sulfonyl]-3-(phenyimethyl)- IH-i ,4-benzodiazepine, dihydrochioride; (R)-7-Bromo-2,3 ,4,5-tetrahydro-li-( I-methyl-imidazol-5-ylmethyl)-4-[(4-methyl-piperidin- 4-yl-ethyl)sulfonyl]-3-(phenylmethyl)-1 H-i ,4-benzodiazepine, dihydrochioride; (R)-7-Cyano- 1,2,3 ,5-tetrahydro-l1-(i H-imidazol-4-ylmethyl)-3-(phenylmethyl)-4H- 1,4benzodiazepine-4-carboxylic acid, isopropyl ester, hydrochloride; (R)-7-Bromo-2,3 ,4,5-tetrahydro-4-[[2-( IH-imidazol- 1-yl)ethyl]sulfonyl]- iH-imidazol-4ylmethyl)-3-(phenylmethyl)-i H-i ,4-benzodiazepine, dihydrochloride; (R)-7-Cyano-2,3 ,4,5-tetrahydro- I H-imidazoi-4-ylmethyl)-4-(propylsulfonyl)-3-(3pyridinylmethyl)- I H-i ,4-benzodiazepine, hydrochloride; 7-Bromo-2,3 ,4,5-tetrahydro- I I H-imidazol-4-ylmethyl)-3 -(phenylmethyl)- I H- 1,4benzodiazepin-5-one, hydrochloride; (R)-7-Bromo-2,3 ,4,5-tetrahydro-li-( iH-imidazol- 1-ylacetyl)-4-(methylsulfonyl)-3 (phenylmethyl)- I H-i ,4-benzodiazepine, trifluoroacetate; ,2,4,5-Tetrahydro- I H-imidazol-4-ylmethyl)-2-(2-phenylethyl)-3H- I ,4-benzodiazepin-3one; 2,3,4,5-Tetrahydro- I I H-imidazoi-4-ylmethyl)-4-(methylsulfonyl)-2-(2-phenylethyl)- I H- 1,4-benzodiazepine, monohydrochloride; ,4,5-Tetrahydro- I I H-imidazol-4-yimethyi)-4-(methylsuifonyl)-7-phenyl-3-(4pyridinylmethyl)- I H-i ,4-benzodiazepine, dihydrochloride; ,4,5-Tetrahydro- I I H-imidazol-2-ylmethyl)-4-(phenylsulfonyl)-3-(phenylmethyi)i H-i ,4-benzodiazepine-7-carbonitri le, hydrochloride; (R)-7-Cyano- 1,2,3 ,5-tetrahydro- I H-imidazol-4-ylmethyl)-N,N-dimethyl-3-(3pyridinylmethyl)-4H-i ,4-benzodiazepine-4-carboxamide, di hydrochloride; (R)-7-Cyano- 1,2,3 ,5-tetrahydro-lI-(1 H-imidazol-4-ylmethyl)-N,N-dimethyl-3-(3pyridinylmethyl)-4H-i ,4-benzodiazepine-4-sulfonamide, dihydrochloride; ,4,5-Tetrahydro- 1 -(4-cyanophenylmethyl)-imidazol-5-ylmethyl)-4- (methylsulfonyl)-3-(phenylmethyl)- 1H-I ,4-benzodiazepine-7-carbonitrile, hydrochloride; o ,4,5-Tetrahydro- 1 -(4-cyanophenylmethyl)-imidazol-4-ylmethyl)-4- 00(methylsulfonyl)-3 -(phenylmethyl)- 1H-i ,4-benzodiazepine-7-carbonitri le, hydrochloride; (R)-4-Benzoyl-7-cyano-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-3 -(phenylmethyl)- 1 H-I ,4-benzodiazepine, monohydrochioride; (R)-7-Cyano-2,3 ,4,5-tetrahydro- 1 -[(1-methyl- I H-imidazol-5-yl)methyl]-3-(pyridin-3ylmethyl)-4-(methylsulfonyl)- I H-i ,4-benzodiazepine, dihydrochioride; (R)-7-Cyano-2,3,4,5-tetrahydro- 1 -[(I1-methyl- I H-imidazol-5-yl)methyl]-3-(pyridin-3- C) 10 ylmethyl)-4-(propylsulfonyl)- I H-i ,4-benzodiazepine, trihydrochioride; (R)-7-Cyano-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-yl)methyl]-3-(pyridin-3-ylmethyl)-4- (phenylsulfonyl)- 1 H-I ,4-benzodiazepine, dihydrochioride; 2,3 ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-4-(methylsulfonyl)-7-phenyl-3- (phenylmethyl)- 1 H-I ,4-benzodiazepine; 1,2,3 ,5-Tetrahydro- 1 I H-imidazol-4-yimethyl)-N-( 1 -naphthalenyl)-7-phenyl-4H- 1,4benzodiazepine-4-carboxamide, monohydrochloride; (S)-7-Bromo-2,3,4,5-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-4-(methylsulfonyl)-3 (phenylmethyl)- 1 H-i ,4-benzodiazepine, hydrochloride; N-[2,3 ,4,5-Tetrahydro- I H-imidazol-4-ylmethyl)-4-(2,3-dimethylbenzoyl)- I H- 1,4benzodiazepin-8-yI]cyclohexanecarboxamide, dihydrochioride; (R)-7-Cyano-N-[2-(dimethylamino)ethyl]-2,3,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)- N-methyl-3 -(phenylmethyl)- 1 H-I ,4-benzodiazepine-4-carboxamide, tri fluoroacetate 7-Bromo-2,3,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-4-(methylsulfonyl)-2-oxo-3- (phenylmethyl)- I H-i ,4-benzodiazepine, trifluoroacetate; (R)-7-Cyano-4-(2-furanylcarbonyl)-2,3 ,4,5-tetrahydro- I H-imidazol-4-ylmethyl)-3- (phenylmethyl)- 1 H-i ,4-benzodiazepine, trifluoroacetate 1); (R)-7-Cyano-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-4-[(4-nitrophenyl)sulfonyl]-3- (phenylmethyl)- 1 H-i ,4-benzodiazepine, trifluroracetate; (R)-7-Cyano-2,3 ,4,5 -tetrahydro- 1 H-imidazol-4-ylmethyl)-4-[[4-(4-methyl- 1 piperazinyl)phenyl]sulfonyl]-3-(phenylmethyl)- IH-I ,4-benzodiazepine, trifluoroacetate; (R)-7-Cyano-2,3,4,5-tetrahydro- I H-imidazol-4-ylmethyl)-4-[[(4dimethylamino)phenyl]sul fonyl] -3 -(phenylmethyl)- IH-i ,4-benzodiazepine, trifluoroacetate; (R)-7-Bromo-4-[[2-(dimethylamino)ethyllsulfonyl]-2,3,4,5-tetrahydro- 1 H-imidazol-4ylmethyl)-3-(phenylmethyl)-4H- 1,4-benzodiazepine, di hydrochloride; (R)-7-Cyano-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-3 -(phenylmethyl)-4-(3pyridinylsulfonyl)- I H-i ,4-benzodiazepine, trihydrochioride; o 2,3,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-4-(methylsulfonyl)-3-(phenylmethyl)- I H- 00 1 ,4-benzo-diazepine, dihydrochioride; (R)-7-Bromo-2,3 ,4,5-tetrahydro- 1 -methyl-I H-imidazol-4-yl)methyl]-4- (methylsulfonyl)-3 -(phenylmethyl)- IH-i ,4-benzodiazepine, dihydrochioride; (R)-4-[[3-(Dimethylamino)propyl]sulfonyl]-2,3 ,4,5-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)- 7-phenyl-3-(phenylmethyl)- 1 H-I ,4-benzodiazepine, dihydrochioride; ID(R)-7-Cyano-2,3,4,5-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-3-(phenylmethyl)- 1H-i ,4benzodiazepine, tri hydrochloride; 4-Butyl-2,3 ,4,5-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-3-(phenylmethyl)- 1 H- 1,4benzodiazepine, tri hydrochloride; (R)-7-Bromo-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-4-[[2-(4morpholinyl)ethyl]sulfonyl]-3-(phenylmethyl)- I H-i ,4-benzodiazepine, dihydrochioride; (R)-7-Bromo-2,3,4,5-tetrahydro-1 -methyl- I H-imidazol-5-yl)methyl]-4-[[2-(4morpholinyl)ethyl]sulfonyl]-3 -(phenylmethyl)- 1H-i ,4-benzodiazepine, d ihydrochloride;, (R)-7-Cyano-l1-(1 H-imidazol-4-ylmethyl)-4-(4-morpholinylsulfonyl)-3-(phenylmethyl)- 1H- I ,4-benzodiazepine, monohydrochioride; (R)-7-Cyano-l1-[(1-methyl-i H-imidazol-5-yl)methyl]-4-[(4-morpholinyl)sulfonyl]-3- (phenylmethyl)- 1 H-i ,4-benzodiazepine, monohydrochioride; (R)-7-Cyano-2,3,4,5-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-4-[(4-aminophenyl)sulfonyl]- 3 -(phenylmethyl)- 1 H-i ,4-benzodiazepine, hydrochloride; 2,3,4,5-Tetrahydro-lI-(1 H-imidazol-4-ylmethyl)-4-[(4-pyridylthio)acetyl]-7-phenyl- IH- 1,4benzodiazepine, dihydrochloride; N-(4-Chlorophenyl)-N'-cyano- 1 ,2,3,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-7-phenyl-4H- I ,4-benzodiazepine-4-imidamide, monohydrochloride; 4-Acetyl-7-bromo- 1,2,4,5, 1 1,3 '-hexahydro- I-(I H-imidazol-4-ylmethyl)spiro[3 H- 1,4benzodiazepine-3,2'- [2H] indene], dihydrochloride; 7-Bromo-4-[3-(dimethylamino)-lI-oxopropyl]-2,3,4,5-tetrahydro-l1-(1 H-imidazol-4ylmethyl)-3-(phenylmethyi)- 1 H-i ,4-benzodiazepine, trifluoroacetate ,4,5-Tetrahydro-l1-(1-methyl-i H-imidazol-5-yimethyl)-4-(phenylsulfonyl)-3- (phenylmethyl)- I H-i ,4-benzodiazepine-7-carbonitrile, monohydrochloride; 2,3 ,4,5-Tetrahydro- I -+(1-methyl- I H-imidazol-5-yl)-methyl]-4-(methyl-sulfonyl)-7-phenyl- __3-(pyridin-3-yl-methyl)-1IH- 1,4-benzodiazepine, hydrochloride trifluoroacetate (1:0.75) salt; 004-[4-(Fluorophenyl)sulfonyl]-2,3 ,4,5-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-2-(2phenylethyl)- 1 H-i ,4-benzodiazepine, monohydrochloride; 7-Bromo-2,3 ,4,5-tetrahydro- 1-(1 H-imidazol-4-yl-methyl)-4-(methyl-sulfonyl)-2-(2phenylethyl)- 1 H-i ,4-benzodiazepine, monohydrochloride; (R)-7-Cyano-2,3 ,4,5-tetrahydro-l1-(1-methyl-i H-imidazol-5-ylmethyl)-4-[[2-( 1morphoiinyl)ethyl]sulfonyl]-3-(phenylmethyl)- 1H-I ,4-benzodiazepine, d ihydrochloride; C) 10 (R)-7-Bromo-2,3 ,4,5-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-4-(methyl-sulfonyl)-3-(4bromophenylmethyl)- 1 H-i ,4-benzodiazepine, hydrochloride; (R)-7-Bromo-2,3 ,4,5-tetrahydro-lI-(1 H-imidazol-4-ylmethyl)-4-(methyl-sulfonyl)-3- (thiazol-4-ylmethyl)- I H-i ,4-benzodiazepine, hydrochloride; (R)-7-Bromo-2,3 ,4,5-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-4-(propyl-sulfonyl)-3-(thiazol- 4-ylmethyi)- I H-i ,4-benzodiazepine, hydrochloride; (R)-7-Bromo-2,3,4,5-tetrahydro-l1-(1 H-imidazol-4-yimethyi)-4-(propylsulfonyl)-3 bromophenylmethyl)- I H-i ,4-benzodiazepine, hydrochloride; (R)-7-Bromo-2,3 ,4,5-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-3 -(Pyridin-3 -ylmethyl)-4- (methylsulfonyl)- 1 H-i ,4-benzodiazepine, trihydrochloride; 20(R)-7-Bromo-2,3,4,5-tetrahydro-lI-(1 H-i -methyl-imidazol-5-ylmethyl)-3 -(pyridin-3ylmethyl)-4-(methylsulfonyi)- 1 H-i ,4-benzodiazepine, dihydrochloride; (R)-7-Cyano-2,3,4,5-tetrahydro-lI-(1 H-imidazol-4-ylmethyl)-4-(phenyl-sulfonyl)-3-(4cyanophenylmethyl)- 1 H-i ,4-benzodiazepine, hydrochloride; (R)-7-Cyano-4-[(N-methyl-N-phenylmethyl)aminosulfonyl]- H-imidazol-4-yI)methyl]- 3-(phenyimethyl)-1I H-I ,4-benzodiazepine, monohydrochloride; (R)-7-Cyano-4-[N-(tetrahydroisoquinolinyl)sulfonyl]- IH-imidazol-4-yl)methyl]-3- (phenylmethyl)- 1 H-i ,4-benzodiazepine, monohydrochloride; (R)-7-Cyano-2,3,4,5-tetrahydro-l1-( IH-imidazol-4-ylmethyl)-4-(phenylsulfonyl)-3-(2thienylmethyl)- 1 H-i ,4-benzodiazepine, hydrochloride; cis-2,3 ,4,5-Tetrahydro- 1,5-bis( 1H-imidazol-4-ylmethyl)-3-(phenylmethyl)- 1H-i benzodiazepine-2-carboxylic acid ethyl ester, trifluoroacetate (R)-7-Cyano-4-[(N-piperidinyl)sulfonyl]- IH-imidazol-4-yl)methyl]-3-(phenylmethyl)- 1 Hl-i ,4-benzodiazepine, monohydrochloride; (R)-7-Cyano-2,3 ,4,5-tetrahydro- 1 H- I -methyl-imidazoi-5-ylmethyl)-3-(phenylmethyl)-4- (2-thienylsulfonyl)- 1 H-I ,4-benzodiazepine, hydrochloride; Co (R)-7-Cyano-2,3 ,4,5-tetrahydro- 1 H-imidazoi-4-yimethyl)-3-(pyridin-3 -ylmethyl)-4-[[2- 00(dimethylamino)ethyl]sulfonyl]- IH-i ,4-benzodiazepine, trihydrochioride; (R)-7-Cyano-2,3,4,5-tetrahydro-l1-(1 H-I -methyl-imidazol-5-ylmethyl)-3 -(phenylmethyl)-4- (propylsulfonyl)- 1 H-I ,4-benzodiazepine, hydrochloride; N-(Cyano)-N'-methyl- 1,2,3,5-tetrahydro-l1-(1 H-imidazol-4-yimethyl)-7-phenyl-4H- 1,4benzodiazepine-4-imidamide, hydrochloride; (R)-7-Cyano-4-[(2-nitrophenyl)-sulfonyl]-2,3,4,5-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-3- C) 10 (phenyl-methyl)- 1 H-i ,4-benzodiazepine, hydrochloride; R)-7-Cyano-4-[(4-methyl-phenyl)sulfonyl]-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyi)- 3-(phenylmethyl)- 1 H-I ,4-benzodiazepine, hydrochloride; (R)-7-Cyano-4-(butylsulfonyl)-2,3,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-3 (phenylmethyl)-1I H-i ,4-benzodiazepine, hydrochloride; (R)-7-Cyano-4-[(2-trifluoro-methylphenyl)sulfonyl]-2,3,4,5-tetrahydro- 1 H-imidazoi-4ylmethyl)-3-(phenylmethyl)-1 H-i ,4-benzodiazepine, hydrochloride; (R)-7-Cyano-4- [(2-trifluoromethoxyphenyl)sulfonyl] -2,3 ,4,5-tetrahydro- I H-imidazol-4yl methyl)-3 -(phenyimethyl)- I H-I ,4-benzodiazepine, hydrochloride; (R)-7-Cyano-4-[(2-methoxy-carbonylphenyi)sulfonyl]-2,3,4,5-tetrahydro- I-(I H-imidazoi-4ylmethyl)-3 -(phenylmethyl)- I Hl-i ,4-benzodiazepine, hydrochloride; (R)-7-Cyano-4- [(2-methyl -sul fonylphenyl)sul fonyl] -2,3 ,4,5 -tetrahydro- I I H- imidazol1-4ylmethyl)-3-(phenylmethyl)-I H-i ,4-benzodiazepine, hydrochloride; (R)-7-Cyano-2,3,4,5-tetrahydro-1-(i H-imidazol-4-ylmethyl)-3-(phenylmethyl)-4-(((4methylsulfonyl)-phenyi)-sulfonyl)- 1 H-I ,4-benzodiazepine; (R)-7-Cyano-2,3,4,5-tetrahydro-l1-(I H-imidazol-4-ylmethyl)-3 -(phenylmethyl)-4-(((4trifluoromethyl)-phenyi)-sul fonyl)- IH-I ,4-benzodiazepine; (R)-7-Cyano-2,3,4,5-tetrahydro-lI-(1 H-imidazol-4-yimethyl)-3 -(phenylmethyl)-4-((3 methoxypropyl)-sulfonyl)- IH-i ,4-benzodiazepine; (R)-7-Cyano-2,3,4,5 -tetrahydro- 1-(1 H-imidazol-4-ylmethyl)-3-(phenylmethyl)-4-((3,4dimethoxyphenyl)-sulfonyl)- I H-i ,4-benzodiazepine; (R)-7-Cyano-2,3,4,5-tetrahydro- I H-imidazol-4-yimethyl)-3-((4-fluorophenyl)methyl)-4- (phenyisul fonyl)- I Hl-I ,4-benzodiazepine; (R)-7-Cyano-4-[(N-cyclopropylmethyl-N-propyl)-aminosulfonyl]- I H-imidazol-4yl)methyl]-3-(phenylmethyl)- I H-I ,4-benzodiazepine; (R)-7-Cyano-4-[(N,N-(dibutylamino))-sulfonyl]-I 1+I( H-imidazol-4-yI)methyl]-3- (phenylmethyl)- I H-I ,4-benzodiazepine; o I,2,3 ,4-Tetrahydro-7-bromo-4-[(I H-imidazol-4-yl)methyl]-2-phenylmethyl-I 00 (methylsul fonyl)quinoxaline; (R)-7-Cyano-2,3 ,4,5-tetrahydro- I H-imidazoi-4-ylmethyl)-3 -(phenyimethyl)-4- ((imidazol-4-yl)methylsulfonyl)- 1 H-i ,4-benzodiazepine; (R)-7-Cyano-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-3-((2-thienyl)methyl)-4- (propylsulfonyl)- 1 H-i ,4-benzodiazepine; I'D (R)-7-Cyano-2,3 ,4,5-tetrahydro- I H-imidazol-4-ylmethyi)-3-((2-thienyl)methyl)-4-((2thienyl)-sulfonyl)- 1 H-I ,4-benzodiazepine; (R)-7-Cyano-2,3,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-3-(phenyimethyl)-4-((3methylthiopropyl)-sulfony)-1I H-i ,4-benzodiazepine; (R)-7-Cyano-2,3,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-3-(phenylmethyl)-4-(((3methylthioxo)-propyl)-sulfonyl)-1I H-I ,4-benzodiazepine; (R)-7-Cyano-2,3,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-3-(phenylmethyl)-4-(((3methylsulfonyl)-propyl)-sulfonyl)- I H-i ,4-benzodiazepine; (R)-7-Cyano-2,3,4,5-tetrahydro- I H-imidazol-4-ylmethyl)-3 -(phenylmethyl)-4-((2methylpropyl)-sulfonyi)- I H-i ,4-benzodiazepine; (R)-7-Cyano-2,3,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-3 -(phenylmethyl)-4-30 (cyclopentyisulfonyl)- I H-i ,4-benzodiazepine; (R)-7-Cyano-2,3,4,5-tetrahydro- I I H-imidazol-4-ylmethyl)-3 -(phenylmethyi)-4-((4,4,4trifluorobutyl)-sulfonyl)- 1 H-i ,4-benzodiazepine; (R)-7-Cyano-2,3,4,5-tetrahydro- 1 I H-imidazol-4-ylmethyl)-3 -(phenylmethyl)-4- ((phenylmethyl)-sulfonyi)- 1 H-i ,4-benzodiazepine; (R)-7-Cyano-2,3,4,5-tetrahydro- 1 I H-imidazoi-4-ylmethyl)-3 -(phenylmethyl)-4-[ benzoyl)-aminomethyl)-thienyl]-sulfonyl]- 1 H-i ,4-benzodiazepine (R)-7-Cyano-2,3,4,5-tetrahydro- 1 H-imidazol-4-yimethyl)-3 -(phenylmethyi)-4-[[2-( 1-(3chioro-5-methyl-pyridin-2-yl))-pyrrolyi]-sulfonyl]- I H-i ,4-benzodiazepine; (R)-7-Cyano-2,3,4,5-tetrahydro- I H-imidazol-4-ylmethyl)-3 -(phenylmethyl)-4-((4carboxyphenyl)-sulfonyi)- 1 H-i ,4-benzodiazepine; (R)-7-Cyano-2,3,4,5-tetrahydro- I H-imidazol-4-ylmethyl)-3 -(phenylmethyl)-4-[((3methyl-i ,2,4-oxadiazoi-5-yl)-phenyl)-sulfonyl]- 1 H-i ,4-benzodiazepine; (R)-7-Cyano-2,3,4,5-tetrahydro- 1 H-imidazoi-4-ylmethyl)-3-(phenylmethyl)-4-((2,5dimethoxyphenyl)-sulfonyl)- 1 H-i ,4-benzodiazepine; (R)-7-Cyano-4-[(N-tetrahydroquinolinyl)sulfonyl]- 1 H-imidazol-4-yl)methyl]-3- (phenylmethyl)- 1 H-i ,4-benzodiazepine; o (R)-7-Cyano-4-[(N,N-bis-[1 -(2-methylpropyl)amino]-sulfonyl]- H-imidazol-4- 00 yI)methyl]-3-(phenylmethyl)-1 H-i ,4-benzodiazepine; (R)-7-Cyano-4-[(N-methyl-N-phenyl)aminosulfonyl]- H-imidazol-4-yI)methyl]-3- (phenylmethyl)- 1 H-i ,4-benzodiazepine; (R)-7-Cyano-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-3-(2-(2,6-dimethylphenyl)ethyl)-4-(methylsulfonyl)- 1 H-I ,4-benzodiazepine; (R)-7-Cyano-2,3 ,4,5-tetrahydro- 1 -(N-phthalimidoethyl)-imidazol-5-ylmethyl)-3- C) 10 (phenylmethyl)-4-(methylsulfonyl)- I H-I ,4-benzodiazepine; (R)-7-Cyano-2,3 ,4,5-tetrahydro-l1-[(2-(N ,N-dimethylamino)-ethyl)-imidazol-5-yimethyl]-3- (phenylmethyl)-4-(methylsulfonyl)-1 H-I ,4-benzodiazepine; (R)-7-Cyano-2,3 ,4,5-tetrahydro- 1 -[(2-aminoethyl)-imidazol-5-ylmethyl]-3-(phenylmethyl)- 4-(methylsulfonyl)- 1 H-i ,4-benzodiazepine; (R)-4-(methanesulfonyl)-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-3-(phenylmethyl)- 1 H-8-oxo-pyrimidino[4,5-e]- 1 ,4-diazepine; (R)-7-Cyano-2,3 ,4,5-tetrahydro- I H-imidazol-4-ylmethyl)-3-((4-(2-methoxyethoxy)phenyl)methyl)-4-(phenylsulfonyl)- 1 H-i ,4-benzodiazepine; (R)-7-Cyano-2,3,4,5-tetrahydro- 1 H-imidazol-4-ylmethyi)-3-((4-(2-(dimethyiamino)ethoxy)-phenyl)methyl)-4-(phenylsulfonyl)- 1 H-I ,4-benzodiazepine; (R)-7-Cyano-2,3,4,5-tetrahydro- I-(I H-imidazol-4-ylsulfonyl)-3-(phenylmethyl)-4- (methylsul fonyl)- 1 H-i ,4-benzodiazepine; (R)-7-Cyano-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylsulfonyl)-3-(phenylmethyl)-4- (propylsulfonyl)- I H-I ,4-benzodiazepine; (R)-7-Cyano-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylsulfonyl)-3-(phenylmethyl)-4- (phenyisulfonyl)- 1 H-i ,4-benzodiazepine; (R)-7-Cyano-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylsulfonyl)-3-(phenylmethyl)-4-(2thienylsulfonyl)- 1 H-i ,4-benzodiazepine; 7-Cyano-2,3,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-3-(R)-[(R)- 1 -phenyl -ethyl] 4- (methylsulfonyl)- 1H-I ,4-benzodiazepine; 7-Cyano-2,3 ,4,5 -tetrahydro- 1 H-i midazol-4-yi methyl)-3 1 -phenyl -ethyl] -4- (propylsulfonyl)- 1 H-I ,4-benzodiazepine; 7-Cyano-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-3-(R)-[(R)- I -phenyl -ethyl]-4- (phenylsulfonyl)- 1 H-i ,4-benzodiazepine; 7-Cyano-2,3,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-3-(R)-[(R)- I -phenyl -ethyl] N_ thienyl)-sulfonyl)- 1 H-i ,4-benzodiazepine; o 7-Cyano-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-3 1 -phenyl -ethyl]-4- 00 (methylsulfonyl)- 1 H-i ,4-benzodiazepine; 7-Cyano-2,3,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-3-(S)-[(R)- I -phenyl -ethyl] -4- (propylsulfonyl)- 1 H-I ,4-benzodiazepine; 7-Cyano-2,3,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-3-(S)-[(R)- 1 -phenyl -ethyl] -4- (phenylsulfonyl)- I H-i ,4-benzodiazepine; 7-Cyano-2,3,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-3-(S)-[(R)- I -phenyl -ethyl] thienyl)-sulfonyl)- 1 H-i ,4-benzodiazepine; 7-Cyano-2,3,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-3-(R)-[(S)- 1 -phenyl -ethyl]-4- (methylsulfonyl)- 1 H-I ,4-benzodiazepine; 7-Cyano-2,3,4,5-tetrahydro- I H-imidazol-4-ylmethyl)-3-(R)-[(S)- I -phenyl -ethyl] -4- (propylsulfonyl)- 1 H-i ,4-benzodiazepine; 7-Cyano-2,3,4,5-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-3-(R)-[(S)- i -pheny I-ethyl] -4- (phenylsulfonyl)- I H-i ,4-benzodiazepine; 7-Cyano-2,3,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-3-(R)-[(S)- I -phenyl -ethyl] thienyl)-suifonyl)- I H-i ,4-benzodiazepine; 7-Cyano-2,3,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-3-(S)-[(S)- 1 -phenylI-ethyl] -4- (methylsulfonyl)- 1 H-I ,4-benzodiazepine; 7-Cyano-2,3,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-3-(S)-[(S)- I -phenylI-ethyl] 4- (propylsulfonyl)- I H-i ,4-benzodiazepine; 7-Cyano-2,3,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-3 1 -phenyl-ethyl]-4- (phenylsulfonyl)- 1 H-i ,4-benzodiazepine; 7-Cyano-2,3,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-3-(S)-[(S)- I -phenyli-ethyl] thienyl)-sulfonyi)- I H-i ,4-benzodiazepine; 7-Cyano-2,3,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-3-(R)-[(R)-phenylcyclopropyl)-4- (methylsulfonyl)- 1 H-i ,4-benzodiazepine; 7-Cyano-2,3,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-3 -(R)+[R)-phenylcyclopropyl)-4- (propylsulfonyl)-1I H-i ,4-benzodiazepine; 7-Cyano-2,3,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-3-(R)-[(R)-phenylcyclopropyl)-4- (phenylsulfonyl)- 1 H-I ,4-benzodiazepine; 7-Cyano-2,3,4,5-tetrahydro- 1 H-imidazol-4-ylmethyi)-3-(R)- [(R)-phenylcyclopropyl)-4- ((2-thienyl)-sulfonyl)- 1 H-i ,4-benzodiazepine; 7-Cyano-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-3-(R)-[(S)-phenylcyclopropyl)-4- (methylsulfonyl)- I H-I ,4-benzodiazepine; o 7-Cyano-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-3-(R)-[(S)-phenylcyclopropyl)-4- 00 (propylsulfonyl)- I H-i ,4-benzodiazepine; 7-Cyano-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-3 -(R)-[(S)-phenylcyclopropyl)-4- (phenylsulfonyl)- I H-I ,4-benzodiazepine; 7-Cyano-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-3-(R)-[(S)-phenylcyclopropyl)-4- ((2-thienyl)-sulfonyl)- 1 H-i ,4-benzodiazepine; 7-Cyano-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-3-(S)-[(R)-phenylcyclopropyl)-4- (methylsulfonyl)- 1 H-i ,4-benzodiazepine; 7-Cyano-2,3,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-3-(S)-[(R)-phenylcyclopropyl)-4- (propylsuifonyl)- 1 H-I ,4-benzodiazepine; 7-Cyano-2,3,4,5-tetrahydro- I H-imidazol-4-ylmethyl)-3 -(S)-[(R)-phenylcyclopropyl)-4- (phenylsulfonyl)- I H-I ,4-benzodiazepine; 7-Cyano-2,3,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-3-(S)-[(R)-phenylcyclopropyl)-4- ((2-thienyl)-sulfonyl)- 1 H-I ,4-benzodiazepine; 7-Cyano-2,3 ,4,5-tetrahydro- I H-imidazol-4-ylmethyl)-3-(S)-[(S)-phenylcyclopropyl)-4- (methylsulfonyl)- 1 H-i ,4-benzodiazepine; 7-Cyano-2,3,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-3-(S)-[(S)-phenylcyclopropyl)-4- (propylsulfonyl)- 1 H-i ,4-benzodiazepine; 7-Cyano-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-3-(S)-[(S)-phenylcyclopropyl)-4- (phenylsulfonyl)- 1 H-i ,4-benzodiazepine; 7-Cyano-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-3-(S)-[(S)-phenylcyclopropyl)-4- ((2-thienyl)-sulfonyl)- 1 H-I ,4-benzodiazepine; (R)-7-Cyano-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-3-(phenylmethyl)-4-[(2-(5- (pyridin-2-yl))-thienyl)-sulfonyl])- I H-I ,4-benzodiazepine; (R)-7-Cyano-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-3 -(phenylmethyl)-4-[(2-(5- (1 ,2-isoxazol-3-yI))-thienyl)-sulfonyl])- 1 H-I ,4-benzodiazepine; (R)-7-Cyano-2,3 ,4,5-tetrahydro- 1 H-imidazol-2-yI)-propyl)-3 -(phenylmethyl)-4- (phenylsulfonyl)- 1 H-i ,4-benzodiazepine; (R)-7-Cyano-2,3 ,4,5-tetrahydro- 1 H-imidazol-2-yl)-propyl)-3-(phenylmethyl)-4- (methylsulfonyl)- I H-i ,4-benzodiazepine; (R)-7-Cyano-2,3 ,4,5-tetrahydro- I H-imidazol-2-yI)-propyl)-3-(phenylmethyl)-4- (propylsulfonyl)- 1 H-i ,4-benzodiazepine; (R)-7-Cyano-2,3,4,5-tetrahydro- I 1 H-imidazol-2-yl)-propyl)-3-(phenylmethyl)-4-((2thienyl)-sulfonyl)- 1 H-i ,4-benzodiazepine;

C.)

00 4-(phenylsulfonyl)- 1 H-i ,4-benzodiazepine; (R)-7-Cyano-2,3,4,5-tetrahydro- 1 1 H-imidazol-2-yl)-ethylsulfonyl)-3-(phenylmethyl)- 4-(methylsulfonyl)- I H-I ,4-benzodiazepine; (R)-7-Cyano-2,3 ,4,5-tetrahydro- 1 1 H-imidazol-2-yl)-ethylsulfonyi)-3-(phenylmethyi)- 4-(propylsulfonyl)- 1 H-i ,4-benzodiazepine; (R)-7-Cyano-2,3 ,4,5-tetrahydro- 1 1 H-imidazol-2-yl)-ethylsulfonyl)-3-(phenylmethyl)- C) 10 4-((2-thienyl)-sulfonyl)- 1 H-i ,4-benzodiazepine; N (R)-7-Cyano-2,3 ,4,5 -tetrahydro- 1 H-imidazol-4-ylmethyl)-3 -(phenyl methyl)-4-(( I oxoethyl)-amino)- I H-i ,4-benzodiazepine; (R)-7-Cyano-2,3 ,4,5 -tetrahydro- I H-imidazol-4-ylmethyl)-3 -(phenylmethyl)-4- (methanesulfonylamino)- 1 H-i ,4-benzodiazepine; (R)-7-Cyano-2,3 ,4,5 -tetrahydro- 1 H-imidazol-4-ylmethyl)-3 -(Phenylmethyl)-4- (phenylsulfonylamino)- 1 H-i ,4-benzodiazepine.

In another embodiment of the invention the compound has the formula: 0 NH

R

N

H

0 wherein R, is selected from Cl, Br, phenyl, pyridyl or cyano and R 2 is selected from substituted aralkyl or substituted heterocycloalkyl.

In yet another embodiment of the invention the compound has the formula 00 O R 1

H

wherein RI is selected from Cl, Br, phenyl, pyridyl or cyano and R 2 is selected from substituted 0 aralkyl or substituted heterocycloalkyl.

c 5 In another embodiment of the invention wherein the compound has the formula

\O

R1

Z'

1

N

R2

N

H

wherein Ri is selected from Cl, Br, phenyl, pyridyl or cyano;

R

2 is selected from substituted aralkyl or substituted heterocycloalkyl;

R

3 is selected from substituted alkyl, substituted aryl or substituted heterocyclo; Zi is selected from CO, SO 2 C0 2 CONHRs, SO 3

SO

2

NR

5 or C(NCN)NR 5

R

5 is selected from hydrogen, lower alkyl, substituted alkyl, aryl or substituted aryl.

In one aspect of the inevntion the compound has the formula 0 R 3

S

R

N

00 N-R2 -(CH2)n+l IN DI O I SProt wherein R, is selected from Cl, Br, phenyl, pyridyl or cyano;

R

2 is selected from substituted aralkyl or substituted heterocycloalkyl;

R

3 is selected from substituted alkyl, substituted aryl or substituted heterocyclo; Zi is selected from CO, SO 2 CO2, CONHRs, SO 3

SO

2 NRs, or C(NCN)NR 5 Prot is triphenylmethyl or Boc; and

R

5 is selected from hydrogen, lower alkyl, substituted alkyl, aryl or substituted aryl.

In one aspect the invention provides a method of treating a synucleinopathic subject, the method comprising, administering to a synucleinopathic subject a farnesyl transferase inhibitor compound of the formula: B DC D C R 4

R

Ax n

N-Z-R

8

N

Y N R,-Ss-Tt 2 3 NR NV R 1

R

2

R

3

R

6

R

7

ID

Sor a stereoisomeric form, or a pharmaceutically acceptable acid or base addition salt form thereof, in a therapeutically effective amount, O wherein 00 nis 1; r, s and t are 0 or 1; p is 0, 1 or 2; \O V, W and X are selected from the group consisting of oxygen, hydrogen, R R 2 and R

SCN

CN N

O

8/ w II II N -N-SO 2 C- R 13

R

14 0 N 0 2 SN-N 0 NR 20

R

21 N NR 2 2

R

1 R R 18 9 1- Z and Y are selected from the group consisting of CHR 9 SO2, SO 3 CO, CO 2 O, NR'O, SO 2 NR" CONR 2 or Z may be absent; R, R 7

R

9 R, R R R R, R 4, R 7 5, R, R R 1

I

9 R R R20, R21 R24, R25, R26, R28

R

29

R

30

R

3 1

R

3 2

R

33

R

34 ,R R 3 6

R

37 and R 38 are selected from the group consisting of hydrogen, lower alkyl, substituted alkyl, aryl and substituted aryl;

R

4 and R 5 are selected from the group consisting of hydrogen, halo, nitro, cyano and U--R 23 U is selected from the group consisting of sulfur, oxygen, NR 24 CO, SO, SO 2

CO

2

,NR

2

CO

2

NR

26

CONR

27

NR

28

SO

2

NR

29 SO2 NR 30

SO

2

NR

31

NR

32 CO, CONR 33 PO2 R 34 and PO3 R 35 or U is absent;

R

2 and R 3 are selected from the group consisting of hydrogen, alkyl, alkoxycarbonyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, aralkyl, cycloalkyl, aryl, substituted aryl, heterocyclo, substituted heterocyclo, cyano, carboxy, carbamyl and substituted carbamyl;

R

8 and R 23 are selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, aralkyl, cycloalkyl, aryl, substituted aryl, heterocyclo and substituted heterocyclo; 00 any two of R2 and R 3 may be joined to form a cycloalkyl group; R, S and T are selected from the group consisting of CH 2 CO and CH(CH 2 )pQ wherein Q 36 37 38 is NR R OR or CN; and A, B, C and D are carbon; with the provisos that V and W are not both oxygen; W and X together may be oxygen only if Z is either absent, 0, NR'o, CHR 9

N(R'

4 N(R' )--SO2 R23 may be hydrogen except when U is SO, SO 2 NR21 CO 2 or NR28 SO 2 and

R

8 may be hydrogen except when Z is SO 2

CO

2 N(R's)--SO0 2 O NR 20

R

21 N NR 22 S- or S In one embodiment of the invention the pharmaceutically acceptable salt is mesylate. In one embodiment of the invention the compound is (R)-7-cyano-2,3,4,5-tetrahydro--(I Himidazol-4-ylmethyl)-3-(phenylmethyl)-4-(2-thienylsulfonyl)-l H-1,4-benzodiazepine, mesylate salt. In yet another embodiment of the innvetion the compound is selected from the group consisting of: 2,3,4,5-Tetrahydro- 1 -(1H-imidazol-4-ylmethyl)-4-( 1 -naphthalenylcarbonyl)- 1 H-1,4benzodiazepine, hydrochloride; 8-Chloro-2,3,4,5-tetrahydro-1-(1 H-imidazol-4-ylmethyl)-4-( -naphthalenylcarbonyl)-1 H-1,4benzodiazepine, hydrochloride; 2,3,4,5-Tetrahydro- 1-(1H-imidazol-4-yl-methyl)-2-methyl-4-(1-naphthalenylcarbonyl)-1H-1,4benzodiazepine, hydrochloride; 2,3,4,5-Tetrahydro-4-( 1 -naphthalenylcarbonyl)- -(phenylmethyl)-1 yl]methyl]-1 H-1 ,4-benzodiazepine, hydrochloride; 2,3,4,5-Tetrahydro-(1H-imidazol-4-yl-methyl)-4-(l -naphthalenylsulfonyl)- I H-1,4benzodiazepine, hydrochloride; ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-3-[2-(methylthio)ethyl]-4-( 1naphthalenylcarbonyl)- I H-I ,4-benzodiazepine, hydrochloride; o 2,3 ,4,5-Tetrahydro- 1 H-imidazol-4-yl-methyl)-N-methyl-N-phenyl-4H- 1 ,4-benzodiazepine- 00 4-carboxamide, hydrochloride; 2-[2,3 ,4,5-Tetrahydro-l1-(1 H-imidazol-4-yl-methyl)- IH-i ,4-benzodiazepin-4yI]sulfonyl]benzoic acid, methyl ester, hydrochloride; 7-Bromo-2,3 ,4,5-tetrahydro-lI-(I H-imidazol-4-ylmethyl)-4-( I-naphthalenylcarbonyl)- 1H- 1,4benzodiazepine, hydrochloride; ID2,3 ,4,5-Tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-4-( I-naphthalenenylcarbonyl)-7-phenyl- 1H- C) 10 1 ,4-benzodiazepine, hydrochloride; 2,3 ,4,5-Tetrahydro-l1-(1 H-imidazol-2-ylmethyl)-4-( 1-naphthalenylcarbonyl)- I H- 1,4benzodiazepine, dihydrochioride; 2,3 ,4,5-Tetrahydro-l1-[3-( 1H-imidazol-2-yl)propyl]-4-( I-naphthalenylcarbonyl)- 1 H- 1,4benzodiazepine, dihydrochioride; 1 -[3-Amino-3-( I H-imidazol-2-yl)propyl]-2,3,4,5-tetrahydro-4-( 1 -naphthalenylcarbonyl)- 1 H- 1 ,4-benzodiazepine, trihydrochloride; 2,3 ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-3-methyl-4-(1 -napthalenylcarbonyl)- I H- 1,4benzodiazepine, hydrochloride; ,4,5-Tetrahydro- 1-(1 H-imidazol-4-ylmethyl)-3-[2-(methylthio)ethyl]-4-( 1naphthalenylmethyl)- I H-i ,4-benzodiazepine, hydrochloride; 2,3,4,5-Tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-9-methyl-4-(1 -naphthalenylcarbonyl)- 1 H- 1,4benzodiazepine, dihydrochioride; 1- [[2-(2-Aminoethyl)- 1 H-imidazol-4-ylmethyl-2,3 ,4,5 -tetrahydro-4-( 1 -naphthalenylcarbonyl)- 1 H-i ,4-benzodiazepine, trihydrochloride; 1 -[[2-Aminomethyl)- 1 H-imidazol-4-yllmethyl]-2,3,4,5-tetrahydro-4-( I -naphthalenylcarbonyl)- I H-i ,4-benzodiazepine, trihydrochioride; N-[2,3,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-4-(1 -naphthalenylcarbonyl)- 1 H-i ,4benzodiazepin-8-yl]acetamide, dihydrochioride; 2,3 ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-4-( 1 -naphthalenylcarbonyl)- 1 H-naphtho[2,3e]-1 ,4-diazepine, dihydrochioride; 2,3 ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-4-( I -naphthal enyl carbonyl)- 8-nitro- 1 H- 1,4benzodiazepine, d ihydrochloridc; 2,3 ,4,5-Tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-4-( 1 -naphthalenylcarbonyl)-8 -amino- I H- 1,4benzodiazepine, dihydrochioride; 7- 69 N-[2,3 ,4,5Tetrahydro- I H-imidazol-4-ylmethyl)-4-( 1 -naphthalenylcarbonyl)- 1 H- 1,4- __benzodiazepin-8-yl]benzamide, dihydrochioride; oN-[2,3 ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-4-( 1 -naphthalenylcarbonyl)- 1 H-I 1,4- 00 benzodiazepin-8-yl]cyclohexanamide, dihydrochioride; 2,3 ,4,5-Tetrahydro- 1 H-imidazol-4-yl)ethyl]-4-( 1 -naphthalenylcarbonyl)- 1 H- 1,4benzodiazepine, dihydrochioride; 2,3 ,4,5-Tetrahydro-l1-[2-( 1 H-imidazol-4-yl)ethyl]-4-( 1-naphthalenylcarbonyl)-7-phenyl- I H- 1 ,4-benzodiazepine, di hydrochloride; ID 7-Bromo-2,3 ,4,5-tetrahydro-l1-[2-( IH-imidazol-4-yl)ethyl]-4-( 1-naphthalenylcarbonyl)- 1H- 1,4benzodiazepine, dihydrochioride; 1 -(2-Aminoethyl)- 1 H-imidazol-5-yI]methyl]-2,3 ,4,5-tetrahydro-4-naphthalenylcarbonyl)-7phenyl- I H-i ,4-benzodiazepine, tri hydrochloride; 2,3 ,4,5Tetrahydro- I H-imidazol-4-ylmethyl)-7-phenyl- I H-I ,4-benzodiazepine-4-carboxylic acid, phenylmethyl ester; 2,3 ,4,5-Tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-7-phenyl-4-[2-(trifluoromethoxy)benzoyl]- 1 H- 1 ,4-benzodiazepine; 1 ,2,3,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-N-methyl-N,7-diphenyl-4H- 1,4benzodiazepine-4-carboxamide, dihydrochioride; 2,3 ,4,5,-Tetrahydro- 1 I H-imidazol-4-ylmethyl)-4-( I -naphthaleneylcarbonyl)-7-( 1piperidinylsulfonyl)- I H-i ,4-benzodiazepine, monohydrochioride; 2,3 ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-4-( 1 -naphthalenylcarbonyl)-7-pyridin-2-yl- I H- I ,4-benzodiazepine, tri hydrochloride; 7-(2-Furanyl)-2,3 ,4,5-tetrahydro-l1-( I H-imidazol-4-ylmethyl)-4-( I -naphthalenylcabonyl)- 1 H- 1 ,4-benzodiazepine, d ihydrochloride; 2,3,4,5-Tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-4-( I-naphthalenylcarbonyl)-7-(2-thienyl)- 1H- 1 ,4-benzodiazepine, dihydrochioride; 2,3 ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-4-( I -naphthalenylcarbonyl)-7-(4-pyridinyl)- 1 H-i ,4-benzodiazepine, trihydrochioride; 2,3 ,4,5-Tetrahydro- 1 H-imidazol-2-yl)propyl]-4-( 1 -naphthalenylcarbonyl)-7-phenyl- 1 H- 1 ,4-benzodiazepine, d ihydrochloride; 2,3,4,5-Tetrahydro-1I,4-bis( 1H-imidazol-4-ylmethyl)-7-phenyl-lIH-I ,4-benzodiazepine, dihydrochioride; 2,3 ,4,5-Tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-4-( 1-naphthalenylmethyl)-7-phenyl- 1H- 1,4benzodiazepine, trifluoroacetate; 2,3 ,4,5-Tetrahydro- I H-imidazol-4-ylmethyl)-7-methoxy-4-( 1 -naphthalenylcarbonyl)- 1 H- 1 ,4-benzodiazepine, dihydrochioride; o 2,3,4,5-Tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-4-( I-naphthalenylcarbonyl)- IH- 1,4- 00 benzodiazepine-7-carboxylic acid, dihydrochioride; 2,3,4,5-Tetrahydro-l1-(1 H-imidazol-5-ylmethyl)-4-( 1-naphthalenylcarbonyl)-7-cyclohexyl- IH- I ,4-benzodiazepine, 2,5 hydrochloride; 7-Butyl-2,3 ,4,5-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-4-( I-naphthalenylcarbonyl)- 1 H- 1,4benzodiazepine, dihydrochioride; INI 1-[[2-(2-Aminoethyl)- IH-imidazol-4-yl]methyl]-2,3,4,5-tetrahydro-4-( 1naphthalenylcarbonyl)-7-phenyl- 1 H-i ,4-benzodiazepine, trihydrochioride; 1 -[[2-(Aminomethyl)- 1 H-imidazol-4-yl]methyl]-2,3 ,4,5-tetrahydro-4-( I -naphthalenylcarbonyl)- 7-phenyl- 1 H-I ,4-benzodiazepine, trihydrochioride; 2,3,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-4-( 1 -naphthalenylcarbonyl)-8-[N,Nbis(phenyl-methyl)amino] -I H-I ,4-benzodiazepine, trihydrochioride; N-[2,3 ,4,5-Tetrahydro-l1-(1 H-imidazol-4-yl-methyl)-4-( 1-naphthalenylcarbonyl)-l1H- 1,4benzodiazepin-8y1]phenylsulfonamide, di hydrochloride; N-Phenyl-2,3,4,5-tetrahydro- 1 H-imidazol-4-yl-methyl)-4-( I -naphthalenylcarbonyl)- 1 H- 1,4benzo-diazepine-7carboxamide, dihydrochioride; N-[2,3 ,4,5-Tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-4-( 1-naphthalenylcarbonyl)- I H- 1,4benzodiazepin-8-yl]-3-methylbenzamide, dihydrochioride; N-[2,3 ,4,5-Tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-4-( 1-naphthalenylcarbonyl)- 1 H- 1,4benzodiazepin-8-yfl-4-methylbenzamide, dihydrochioride; 3 -Chiloro-N -tetrahydro- 1 H -imidazol-4-yl -methyl)-4-( I -naphthal enylIcarbonyl)- I H- I ,4-benzo-diazepin-8-yl]benzamide, dihydrochioride;.

7-Bromo-2,3 ,4,5,-tetrahydro-l1-[[2-[(dimethylamino)-methyl]- IH-imidazol-4-yljmethyl]-4-( 1naphthalenylcarbonyl)- 1 H-i ,4-benzodiazepine, dihydrochioride; 7-(4-Chlorophenyl)-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-4-( 1naphthalenylcarbonyl)- 1 H-i ,4-benzodiazepine, di hydrochloride; 7-(3-Aminophenyl)-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-4-( 1naphthalenylcarbonyl)- I H-I ,4-benzodiazepine, tri hydrochloride; 1 -Methyl-N-[2,3,4,5-tetrahydro- I H-imidazol-4-ylmethyl)-4-( 1 -naphthalenylcarbonyl)- 1 H- I ,4-benzodiazepin-8-y]- -1 H-pyrrole-2-carboxamide, trihydrochioride; N-[2,3 ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-4-( 1 -naphthalenylcarbonyl)- 1 H- 1,4benzodiazepin-8-yl] -3 -furancarboxamide, dihydrochioride; 7-(3-Chlorophenyl)-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-4-( I- __naphthalenylcarbonyl)- I H-I ,4-benzodiazepine, dihydrochioride; o 2-Methyi-N-[2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-4-( 1 -naphthalenylcarbonyl)- 1 Hl- 00 1 ,4-benzodiazepin-8-yl] benzamide, di hydrochloride; N-Phenyl-N'-[2,3 ,4,5-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-4-( 1-naphthalenylcarbonyl)- IH- 1 ,4-benzodiazepin-8-yl] urea, dihydrochioride; 2,3,4,5-Tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-4-( 1-naphthalenylcarbonyl)-7-(3-pyridinyl)- I H-i ,4-benzodiazepine, trihydrochioride; 2,3,4,5 -Tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-9-methoxy-4-( 1-naphthalenylcarbonyl)- 1H- 1 ,4-diazepine, dihydrochioride; (R)-2,3,4,5-Tetrahydro-lI-(1 H-imidazol-4-ylmethyl)-3-[2-(methylthio)ethyl]-4-( 1naphthalenylcarbonyl)- I H-I ,4-benzodiazepine, hydrochloride; 2,3,4,5-Tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-4-( I-naphthalenylcarbonyl)-3-(phenylmethyl)- 1 H-i ,4-benzodiazepine, hydrochloride; 2,3,4,5-Tetrahydro-3-(2-hydroxyethyl)- I-(I H-imidazol-4-ylmethyl)-4-(I naphthalenylcarbonyl)- 1 H-I ,4-benzodiazepine, trifluoroacetate; (S)-2,3,4,5-Tetrahydro- I-(I H-imidazol-4-ylmethyl)-4-( I-naphthalenylcarbonyl)-3- (phenylmethyl)- 1 H-I ,4-benzodiazepine, trifluoroacetate; 4-Acetyl-7-bromo-2,3 ,4,5-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-3 -(phenylmethyl)- 1H- 1,4benzodiazepine, hydrochloride; 7-Bromo- 1,2,3 ,5-tetrahydro-lI-(I H-imidazol-4ylmethyl)-3-(phenylmethyl)-4H- 1,4benzodiazepine-4-carboxamide, trifluoroacetate; 7-Bromo-2,3 ,4,5-tetrahydro-lI-(I H-imidazol-4-ylmethyl)-4-(methylsulfonyl)-3 -(phenylmethyl)- 1 H-i ,4-benzodiazepine, hydrochloride; 4-Acetyl-2,3,4,5-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-7-phenyl-3 -(phenylmethyl)- 1 H- 1,4benzodiazepine, trifluoroacetate; 4-Acetyl-7-bromo-3 -[(4-chlorophenyl)methyl]-2,3 ,4,5-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)- 1 H-I ,4-benzodiazepine, d ihydrochloride; 4-Acetyl-2,3,4,5-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-3-(phenylmethyl)- 1 H-naphtho[2,3-e]- 1 ,4-diazepine, monohydrochioride; N-Cyclohexyl-N'-[2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-4-( 1 -naphthalenylcarbonyl]- I H-i ,4-benzodiazepin-8-yl]urea, dihydrochioride; 2,3,4,5-Tetrahydro- I H-imidazol-4-ylmethyl)-4-(methylsulfonyl)-3-(phenylmethyl)- I Hnaphtho [2,3 -1 ,4-diazepine, monohydrochioride; 2,2-Dimethyl-N-[2,3 ,4,5-tetrahydro- I H-imidazol-4-ylmethyl)-4-( 1 -naphthalenylcarbonyl)- FH-i ,4-benzodiazepin-8-yl]propanamide, dihydrochioride; o 2,3 ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-4-( 1-naphthalenylsulfonyl)-7-phenyl- 1 H- 1,4- 00 benzodiazepine, monohydrochioride; 4-Acetyl-7-bromo-2,3,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-3-(2-naphthalenylmethyl)- 1 H-I ,4-benzodiazepine, dihydrochioride; 4-Acetyl-7-bromo-2,3,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-3-( 1 -naphthalenylmethyl)- 1 H-i ,4-benzodiazepine, dihydrochioride; 7-(2-Chlorophenyl)-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-4-( I C) 10 naphthalenylcarbonyl)- 1 H-i ,4-benzodiazepine, dihydrochioride; 2,3 ,4,5-Tetrahydro- I H-imidazol-4-ylmethyl)-7-phenyl- I Hl-i ,4-benzodiazepine, monohydrochioride; 1 -Methyl-N-[2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-4-( I -naphthalenylcarbonyl)- 1 Hl- I ,4-benzodiazepin-8-yl] -2-piperidinecarboxamide, trihydrochioride; N-[2,3,4,5-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-4-( 1-naphthalenylcarbonyl)- 1 H- 1,4benzodiazepin-8-yl]-4-morpholinecarboxamide, dihydrochio ride; 2,3 ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-4-( 1 -naphthalenylcarbonyl)- I H- 1,4benzodiazepin-8-yl]-3-methylbutanamide, dihydrochioride; 1,2,3 ,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-N,N,7-triphenyl-4H- I ,4-benzodiazepin carboxamide, dihydrochioride; 1 ,2,3,5-Tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-3-(phenylmethyl)-4H-naphtho[2,3-e]- 1,4diazepine-4carboxyl ic acid, methyl ester, monohydrochioride; 2,3 ,4,5-Tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-7-phenyl-4-[(4-phenyl-1I,2,3 yl)carbonyl]- 1 H-I ,4-benzodiazepine, trifluoroacetate; [(Cyclohexylamino)carbonyl] amino] -2,3 ,4,5-tetrahydro- I H-imidazol-4-ylmethyl)-3- (phenylmethyl)- 1 Hl-I ,4-benzodiazepine-4-carboxylic acid, 1, 1 -dimethylethyl ester; 2,3 ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-8-[[(4-methylphenyl)sulfonyl]amino]-3- (phenylmethyl)- 1 H-i ,4-benzodiazepine-4-carboxylic acid, 1, 1 -dimethyl ethylIester; 7-Bromo- 1 ,2,3,4-tetrahydro- 1 H-imidazol-4-ylmethyl)-3-(phenylmethyl)-5 H- 1,4benzodiazepin-5-one, di hydrochloride; 2,3 ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-4-[ I -oxo-3-( 1 -piperidinyl)propyl]-7-phenyl- I H-I ,4-benzodiazepine, trihydrochioride; 2,3 ,4,5-Tetrahydro- 1 I H-imidazol-4-ylmethyl)-7-phenyl-4-(4-quinolinylcarbonyl)- I H- 1,4benzodiazepine, tri hydrochloride; -Bromo-3 -pyridinyl)carbonyl] -2,3 ,4,5 ,tetrahydro- 1 H-imidazol-4-ylmethyl)-7-phenyl- I H-I ,4-benzodiazepine, trihydrochioride; o(S)-4-[2-(Dimethylamino)- 1 -oxo-3-phenylpropyl]-2,3,4,5-tetrahydro- I -(]Himdzl4 00 ylrnethyl)-7-phenyl- 1 H-i ,4-benzodiazepine, trihydrochioride; 2,3 ,4,5-Tetrahydro-4-[4-hydroxy-3-(4-morpholinyl-methyl)benzoyl]- 1 H-imidazol-4yimethyl)-7-phenyl- 1 H-i ,4-benzodiazepine, trihydrochioride; (S)-2,3,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-4-[( 1 -methyl-2-pyrrolidinyl)carbonyl]-7phenyl- 1 H-I ,4-benzodiazepine, trihydrochioride; IND 2,3 ,4,5-Tetrahydro- I H-imidazol-4-ylmethyl)-7-phenyi-4-[[2-(Propylthio)-3- C) 10 pyridinyl]carbonyl]- 1 H-i ,4-benzodiazepine, trihydrochioride; 4-[(2-Chloro-6-methyl-4-pyridinyl)carbonyl]-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-7phenyl- 1 H-i ,4-benzodiazepine, tri hydrochloride; 2,3 ,4,5-Tetrahydro- 1I-(]I H-imidazol-4-ylmethyl)-7-phenyl-4-[[2-(phenylthio)-3pyridinyl] carbonyl] -1H-I ,4-benzodiazepine, trihydrochioride; 2,3 ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-4-[[2-(4-methylphenoxy)-3piperidinyl]carbonyi]-7-phenyl- 1 H-i ,4-benzodiazepine, trihydrochioride; 2,3 ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-4-[(2-methoxy-3-pyridinyl)carbonyl]-7-phenyl- 1 H-i ,4-benzodiazepine, tri hydrochloride; 2,3 ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-7-phenyl-4-[(5-phenyl-4-oxazolyl)carbonyl]- 1 H-i ,4-benzodiazepine, dihydrochioride; 4-Acetyl-2,3 ,4,5-tetrahydro- I H-imidazol-4-ylmethyl)-7-phenyl- 1 H-i ,4-benzodiazepine, dihydrochioride; 2,3 ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-7-phenyl-4-[(tetrahydro-3-furanyl)carbonyl]- 1 H-i ,4-benzodiazepine, dihydrochioride; 2,3 ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-4-[(2-methoxyethoxy)acetyl]-7-phenyl- 1 H- 1,4benzodiazepine, di hydrochioride; 2,3 ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-4-(4-(4-morpholinylmethyl)benzoyl]-7 2,3 ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-4-(4-(4-morpholinylmethyl)benzoyl]-7 2,3 ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-4-[4-(methylsulfonyl)benzoyl]-7-phenyl- 1 H- 1 ,4-benzodiazepine, di hydrochloride; 2,3 ,4,5-Tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-4-[ 1-oxo-3-(phenylsulfonyl)propyl]-7-phenyl- 1 H-i ,4-benzodiazepine, di1hydrochloride; 2,3 ,4,5-Tetrahydro-l1-(1 H-imidazoi-4-ylmethyl)-7-phenyl-4-(3 -pyridinylacetyl)-l1H- 1 ,4benzodiazepine, trihydrochioride; 2,3,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-7-phenyl-4-(2-quinoxalinylcarbonyl)- 1 H- 1,4benzodiazepine, tetrahydrochioride; o 2,3 ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-4-(4-isoquinolinylcarbonyl)-7-phenyl- 1H- 1,4- 00 benzodiazepine, trihydrochioride; 4-[(2-Chloro-3-pyridinyl)carbonyl]-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-7-phenyl- 1 H-i ,4-benzodiazepine, trihydrochioride; 2,3,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-7-phenyl-4-(3 -pyridinylcarbonyl)- I H- 1,4benzodiazepine, trihydrochioride; 1-10 4-[(2,6-Dimethoxy-3-pyridinyl)carbonyl]-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-7- C) 10 phenyl- 1 H-I ,4-benzodiazepine, tri hydrochloride; 2,3 ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-7-phenyl-4-(2-pyrazinylcarbonyl)- 1 Hl- 1,4benzodiazepine, tetrahydrochioride; 4-(2-Ethoxybenzoyl)-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-7-phenyl- I H- 1,4benzodiazepine, dihydrochioride; 4-[3-(Dimethylamino)benzoyl]-2,3,4,5-tetrahydro-lI-(I H-imidazol-4-ylmethyl)-7-phenyl- IH- I ,4-benzodiazepine, tri hydrochloride; 2,3 ,4,5-Tetrahydro- I H-imidazol-4-ylmethyl)-7-phenyl-4-[( 1 -phenylcyclopropyl)carbonyl]- 1 H-I ,4-benzodiazepine, dihydrochioride; 4+[Bicyclo[4.2. 0]octa- 1,3 ,5-trien-7-yl)carbonyl]-2,3 ,4,5-tetrahydro-l1-(1 H-imidazol-4ylmethyl)-7-phenyl- 1 H-i ,4-benzodiazepine, dihydrochioride; 4-Benzoyl-2,3 ,4,5-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-7-phenyl- 1H-I ,4-benzodiazepine, dihydrochioride; 4-(2-Chlorobenzoyl)-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-7-phenyl- I Hl-I ,4benzodiazepine, d ihydrochloride; 4-(2,3-Dichlorobenzoyl)-2,3,4,5-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-7-phenyl- 1H- 1,4benzodiazepine, di hydrochioride; ,4,5-Tetrahydro-l1-( IH-imidazol-4-ylmethyl)-7-phenyl- 1H-i ,4-benzodiazepin-4yl] carbonyl]phenyl]acetamide, dihydrochioride; 2,3 ,4,5-Tetrahydi'o-l1-(1 H-imidazol-4-ylmethyl)-4-(2-phenoxybenzoyl)-7-phenyl- 1 H- 1,4benzodiazepine, dihydrochioride; 2,3 ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-4-(2-methoxybenzoyl)-7-phenyl- 1 H- 1,4benzodiazepine, d ihydrochloride; 4-(2,3 -Dimethoxybenzoyl)-2,3 ,4,5-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-7-phenyl- IH- 1,4benzodiazepine, dihydrochioride; 4-(2,4-Dimethoxybenzoyl)-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-7-phenyl- 1 H- 1,4benzodiazepine, dihydrochioride; o 4-(2,5-Dimethoxybenzoyl)-2,3 ,4,5-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-7-phenyl- 1H- 1,4- 00 benzodiazepine, dihydrochioride; 4-(2,6-Dimethoxybenzoyl)-2,3 ,4,5-tetrahydro- I H-imidazol-4-ylmethyl)-7-phenyl- 1 H- 1,4benzodiazepine, dihydrochioride; 4-(2,3-Dihydroxybenzoyl)-2,3 ,4,5-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-7-phenyl- 1H- 1,4benzodiazepine, dihydrochioride; ID4-([ 1,1'-Biphenyl]-2-ylcarbonyl)-2,3 ,4,5-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-7-phenyl- 1H- C) 10 1,4-benzodiazepine, dihydrochioride; 2,3 ,4,5Tetrahydro- 1 H-imidazol-4-ylmethyl)-4-(2-methylbenzoyl)-7-phenyl- 1 H- 1,4benzodiazepine, dihydrochioride; 4-(2,3-Dimethylbenzoyl)-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-7-phenyl- 1 H- 1,4benzodiazepine, dihydrochioride; 4-(3-Cyanobenzoyl)-2,3,4,5-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-7-phenyl- 1H- 1,4benzodiazepine, di hydrochloride; 4-(3-Chlorobenzoyl)-2,3,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-7-phenyl- 1 H- 1,4benzodiazepine, dihydrochioride; 2,3,4,5-Tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-4-(3-phenoxybenzoyl)-7-phenyl- 1H- 1,4benzodiazepine, d ihydrochloride; 2,3 ,4,5-Tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-4-(3-methoxybenzoyl)-7-phenyl- IH- 1,4benzodiazepine, dihydrochioride; 4-(3 ,4-Dimethoxybenzoyl)-2,3 ,4,5-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-7-phenyl- 1H- 1,4benzodiazepine, d ihydrochloride; 4-(3 ,5-Dimethoxybenzoyl)-2,3 ,4,5-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-7-phenyl- 1H- 1,4benzodiazepine, di hydrochloride; 2,3 ,4,5-Tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-4-(3-methylbenzoyl)-7-phenyl- IH- 1,4benzodiazepine, di hydrochloride; 1,2-Dioxo-2-phenylethyl)-2,3,4,5-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-7-phenyl- IH- 1,4benzodiazepine, d ihydrochloride; 4-[(2-Ethoxy- I-naphthalenyl)carbonyl]-2,3,4,5-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-7phenyl- 1 H-I ,4-benzodiazepine, dihydrochioride; 2,3,4,5-Tetrahydro- 1-(1 H-imidazol-4-ylmethyl)-4-(2-naphthalenylcarbonyl)-7-phenyl- 1H- 1,4benzodiazepine, dihydrochioride; 4-(Fluorophenylacetyl)-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-7-phenyl- 1 H- 1,4benzodiazepine, di hydrochloride; o 4-(Diphenylacetyl)-2,3 ,4,5-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-7-phenyl- 1H- 1,4- 00 benzodiazepine, di hydrochloride; 2,3 ,4,5-Tetrahydro-4-(2-hydroxy-l1-oxo-2-phenylpropyl)- 1-(1 H-imidazol-4-ylmethyl)-7-phenyl- 1 Hl-i ,4-benzodiazepine, dihydrochioride; 2,3 ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-4-( 1 H-indol-2-ylcarbonyl)-7-phenyl- 1 Hl- 1,4benzodiazepine, d ihydrochloride; ID2,3,4,5-Tetrahydro- 1-(1 H-imidazol-4-ylmethyl)-4-( IH-indol-3-ylcarbonyl)-7-phenyl- 1 H- 1,4benzodiazepine, dihydrochioride; 2,3 ,4,5-Tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-4-( I H-indol-5-ylcarbonyi)-7-phenyl- 1 H- 1,4benzodiazepine, di hydrochloride; 2,3 ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-4-[( 1-methyl- I H-indol-2-yI)carbonyl]-7phenyl- 1 H-i ,4-benzodiazepine, dihydrochioride; 4-(2-Benzofuranylcarbonyl)-2,3 ,4,5-tetrahydro- I H-imidazol-4-ylmethyl)-7-phenyl- 1 H- 1,4benzodiazepine, dihydrochioride; 2,3 ,4,5-Tetrahydro- 1-(1 H-imidazol-4-ylmethyl)-7-phenyl-4-(3 -pyridinylcarbonyl)- I H- 1,4benzodiazepine, N-oxide, dihydrochioride; 2,3 ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-7-phenyl-4-(2-pyridinylcarbonyl)- I H- 1,4benzodiazepine, tri hydrochloride; 2,3,4,5-Tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-7-phenyl-4-(2-quinolinylcarbonyl)- 1H- 1,4benzodiazepine, trihydrochioride; 2,3 ,4,5-Tetrahydro- 1 H-imidazoi-4-ylmethyl)-7-phenyl-4-( 1 -isoquinolinylcarbonyl)- 1 H- 1,4benzodiazepine, trihydrochioride; 4-(3-Chloro-2-nitrobenzoyl)-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-yimethyl)-7-phenyl- 1 H- 1,4benzodiazepine, d ihydrochloride; 2,3,4,5-Tetrahydro- 1-(1 H-imidazol-4-ylmethyl)-4-(2-nitrobenzoyl)-7-phenyl- IH- 1,4benzodiazepine, dihydrochioride; 2,3 ,4,5-Tetrahydro-l1-( I H-imidazol-4-ylmethyl)-4-(3-methoxy-2-nitrobenzoyl)-7-phenyl- 1H- 1 ,4-benzodiazepine, dihydrochioride; 2,3 ,4,5-Tetrahydro- 1 H-irnidazol-4-ylmethyl)-4-( 1 H-indol-4-ylcarbonyl)-7-phenyl- I H- 1,4benzodiazepine, dihydrochioride; 4-[(2,6Dihydroxy-3-naphthalenyl)carbonyl]-2,3,4,5-tetrahydro- 1-(1 H-imidazol-4-ylmethyl)-7phenyl- 1 H-i ,4-benzodiazepine, dihydrochloride; 77 4-(l1 H-Benzimidazol-5-ylcarbonyl)-2,3,4,5-tetrahydro- I H-imidazol-4-ylmethyl)-7-phenyl- I_ H-i ,4-benzodiazepine, trihydrochioride; o 4-(1I H-Benzotriazol-5-ylcarbonyl)-2,3,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-7-phenyl- I H- 00 1 ,4-benzodiazepine, d ihydrochloride; 2,3 ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-4-[(4-methoxy-2-quinolinyl)carbonyl]-7phenyl- I H-I ,4-benzodiazepine trihydrochioride; ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-7-phenyl- 1 H-i ,4-benzodiazepin-4yI]carbonyl]phenyl]-acetamide, dihydrochioride; IND 2,3,4,5 -Tetrahydro- I H-imidazol-4-ylmethyl)-4-(2-methyl- 1 -oxo-2-phenylpropyl)-7-phenyl- 1 H-i ,4-benzodiazepine, dihydrochioride; 4-[2-(Dimethylamino)benzoyl]-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-7-phenyl- 1 H- 1 ,4-benzodiazepine, trihydrochioride; 4-(3-Ethoxybenzoyl)-2,3,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-7-phenyl- 1 H- 1,4benzodiazepine,dihydrochloride; 2,3 ,4,5-Tetrahydro-4-(2-hydroxy[ 1,1 '-biphenyl]-3-ylcarbonyl)- 1-(1 H-imidazol-4-ylmethyl)-7phenyl- 1 H-i ,4-benzodiazepine, dihydrochioride; 2,3 ,4,5-Tetrahydro-4-[2-[(2-hydroxyethyl)thio]benzoyl]- I-(1 H-imidazol-4-ylmethyl)-7-phenyl- 1 H-I ,4-benzodiazepine, d ihydrochloride; 2,3,4,5 -Tetrahydro- 1 H-imidazol-4-ylmethyl)-4- [(2-methoxy- 1 -naphthalenyl)carbonyl] -7phenyl- 1 H-I ,4-benzodiazepine, dihydrochioride; 2,3,4,5-Tetrahydro-4-[(2-hydroxy-4-qiunolinyl)-carbonyl]- 1 H-imidazol-4-ylmethyl)-7phenyl- I H-I ,4-benzodiazepine, dihydrochioride; ,4,5-Tetrahydro- 1 I H-imidazol-4-ylmethyl)-7-phenyl- I H-i ,4-benzodiazepin-4yl]carbonyl]benzamide, dihydrochioride; 1,1-Dimethylethyl)-2-[[2,3 ,4,5-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-7-phenyl- 1H- 1,4benzodiazepin-4-yl]carbonyl]benzamide, dihydrochioride; N-(4-Fluorophenyl)-N'-[3-[[2,3 ,4,5-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-7-phenyl- 1 H- 1,4benzodiazepin-4-yl]carbonyl]phenyl] urea, dihydrochioride; 2,3,4,5 -Tetrahydro- 1 H-imidazol-4-ylmethyl)-4-[(3-methyl-4-oxo-2-phenyl-4H-benzopyran- 8-yl)carbonyl]-7-phenyl- 1 H-I ,4-benzodiazepine, di hydrochloride; 2,3 ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-7-phenyl-4-[3-(trifluoromethoxy)benzoyl]- I H- I ,4-benzodiazepine, dihydrochioride; 4-(2-Cyanobenzoyl)-2,3 ,4,5-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-7-phenyl- I H- 1,4benzod iazepi ne,d ihydrochloride; 2,3,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-4-[2-[[(4- __methophenyl)sul fonyl] amino] benzoyl] -7-phenylI- I H-i ,4-benzodiazepine, di hydrochloride; o 2,3,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-7-phenyl-4-(6-quinolinylcarbonyl)- 1 H- 1,4- 00 benzodiazepine, trihydrochioride; 2,3,4,5-Tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-7-phenyl-4-(8-quinolinylcarbonyl)- 1 H- 1,4benzodiazepine, trihydrochioride; 4-(Benzo[b]thiophen-2-ylcarbonyl)-2,3,4,5-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-7-phenyl- 1 H-i ,4-benzodiazepine, dihydrochioride; IND4-[[4-(Dimethylamino)-l1-naphthalenyl]-carbonyl] -2,3,4,5-tetrahydro-l1-(1 H-imidazol-4ylmethyl)-7-phenyl- 1 H-i ,4-benzodiazepine, trihydrochioride; 2,3,4,5-Tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-7-phenyl-4-( IH-purin-6-ylcarbonyl)- IH- 1,4benzodiazepine, tri hydrochloride; 2,3,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-4-(methoxyphenylacetyl)-7-phenyl- 1 H- 1,4benzodiazepine, dihydrochioride; 2,3,4,5-Tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-4-[(5-methyl- 1-phenyl- 1H-pyrazol-4yl)carbonyl]-7-pheny!- 1 H-i ,4-benzodi azepine,tri hydrochloride; 2,3,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-4-[2-(2-methylphenyl)- 1 -oxopropyl]-7-phenyl- 1 H-i ,4-benzodiazepine, dihydrochioride; 2,3,4,5 -Tetrahydro- 1 H-imidazol-4-ylmethyl)-7-phenyl-4- [(tetrahydro-4-phenyl-2H-pyran-4yl)carbonyl]- 1 H-i ,4-benzodiazepine, di hydrochloride; 2,3,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-4-[2-(methylphenylamino)benzoyl]-7-phenyl- I H-I ,4-benzodiazepine, tri hydrochloride; 2,3,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-7-phenyl-4-(4quinolinylcarbonyl)- I H-phenyl- I H-i ,4-benzodiazepine, tri hydrochloride; 2,3,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-7-phenyl-4-(4-quinolinylcarbonyl)- 1 H- 1,4benzodiazepine, N-oxide, dihydrochioride; N-Methyl-N-(2-pyridinyl methyl)-2-[[2,3 ,4,5 -tetrahydro- 1 H-imidazol-4-ylmethyl)-7-phenyl- 1 H-i ,4-benzodiazepin-4-yl] carbonyl] benzaniide, trihydrochioride; 2,3,4,5-Tetrahydro- 1 H-imidazol-4-ylrnethyl)-4-(3-isoquinolinylcarbonyl)-7-phenyl- 1 H- 1,4bezodiazepine, trihydrochioride; 2,3,4,5-Tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-4-[(2-naphthalenylthio)acetyl]-I1H- 1,4benzodiazepine, trifluoroacetate ,4-Dimethoxyphenyl)- 1-oxopropyl]-2,3,4,5-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)- 1H- 1 ,4-benzodiazepine, trifluoroacetate 79 1,1 '-Biphenyl]-4-ylacetyl)-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)- 1 H- 1,4- __benzodiazepine, trifluoroacetate o 2,3 ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-4-(2-naphthalenylacetyl)- I H- 1,4- 00 benzodiazepine,trifluoroacetate 1,1'-Biphenyl]-2-ylcarbonyl)-2,3 ,4,5-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)- 1H- 1,4benzodiazepine, trifluoroacetate 2,3,4,5-Tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-4-[(2-phenyl-4-quinolinyl)carbonyl]- IH- 1,4benzodiazepine, trifluoroacetate IND 2,3 ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-4-(3-pyridinylacetyl)- 1 H-i ,4-benzodiazepine, trifluoroacetate 4-(9H-Fluoren-9-ylacetyl)-2,3 ,4,5-tetrahydro- I H-imidazol-4-ylmethyl)- 1 H- 1,4benzodiazepine, tri fluoroacetate (S)-4-[2-(Dimethylamino)- 1 -oxo-3-phenylpropyl]-2,3 ,4,5-tetrahydro- I H-imidazol-4ylmethyl)- 1 H-I ,4-benzodiazepine, trifluoroacetate ,4,5-Tetrahydro- 1 H-im idazol-4-ylmethyl)-4- [(2-oxo-4-phenyl -3 -oxazo lid inyl)acetyl 1 H-i ,4-benzodiazepine, trifluoroacetate 4-(9-Acridinylcarbonyl)-2,3,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)- 1 H-I ,4benzodiazepine, trifluoroacetate 2,3 ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-4-(3-phenoxybenzoyl)- I H-i ,4-benzodiazepine, trifluoroacetate 2,3 ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-4-[[4'-(trifluoromethyl)[ 1,1 '-biphenyl]-2yI]carbonyl]- 1 H-i ,4-benzodiazepine, trifluoroacetate 2,3 ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-4-(4-phenoxybenzoyl)- 1 H-I ,4-benzodiazepine, trifluoroacetate 2,3 ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-4-(2-naphthalenylcarbonyl)- 1 H- 1,4benzodiazepine, trifluoroacetate 2,3,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-4-( 1 -oxo-4-phenylbutyl)- 1 H- 1,4benzodiazepine, trifluoroacetate 2,3 ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-4-[(2-phenoxyphenyl)acetyl]- 1 H- 1,4benzodiazepine, trifluoroacetate 2,3 ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-4-[2-[(4-methylphenyl)sulfinyl]benzoyl]- I Hl- 1 ,4-benzodiazepine, trifluoroacetate 2,3 ,4,5-Tetrahydro- 1 H-imidazol-4-yimethyl)-4-[2-[(phenylmethyl)amino]benzoyl]- I H- 1,4benzodiazepine, trifluoroacetate 1,2,3 ,5-Tetrahydro- 1 H-imidazol-4y1-methyl)-N,N-diphenyl-4H-1I,4-benzodiazepine- 4carboxamide, hydrochloride;, o 1,2,3 ,5-Tetrahydro- I H-imidazol-4-yl-methyl)-a,7-diphenyl-4H- 1 ,4-benzodiazepine-4-acetic 00 acid, methyl ester, hydrochloride; 4-Acetyl-2,3,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-3-(phenylmethyl)- I H- 1,4benzodiazepine, hydrochloride; (R)-7-Bromo-2,3 ,4,5-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-4-(methylsulfonyl)-3 (phenylmethyl)- 1 H-I ,4-benzodiazepine, hydrochloride; IND (R)-2,3,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-4-(methylsulfonyl)-3-(phenylmethyl)- 1 H- C) 10 1 ,4-benzodiazepine-7-carbonitrile, monohydrochioride; (R)-4-Acetyl-2,3 ,4,5-tetrahydro- 1-(1 H-imidazol-4-ylmethyl)-7-phenyl-3 -(phenylmethyl)- 1H- I ,4-benzodiazepine, monohydrochioride; 7-Bromo-4-[[2-(dimethylamino)ethyl]sulfonyi]-2,3,4,5-tetrahydro- I H-imidazol-4-ylrnethyl)- 3-(phenylmethyl)-4H- 1,4-benzodiazepine, trifluoroacetate 2,3,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-7-phenyl-4-[( 1,2,3 ,4-tetrahydro- I quinolinyl)carbonyl]- 1 H-i ,4-benzodiazepine, monohydrochloride; N-Ethyl-i ,2,3,5-tetrahydro- I H-imidazol-4-ylmethyl)-N,7-diphenyl-4H- I ,4-benzodiazepine- 4-carboxamide, monohydrochloride; 4-[(2,3-Dihydro- IH-indol-1I-yl)carbonyl]-2,3 ,4,5-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-7phenyl- 1 H-i ,4-benzodiazepine, monohydrochloride; 2,3,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-4-(methylsulfonyl)-3-(phenylmethyl)-7-(4pyridinyl)- 1 H-i ,4-benzodiazepine, trihydrochloride; (R)-4-[t2-(Dimethylamino)ethyl]sulfonyl]-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-7phenyl-3-(phenylmethyl)- IH-I ,4-benzodiazepine, trifluoroacetate [2,3 ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-4-( I -naphthalenylcarbonyl)- 1 H- 1,4benzodiazepin-8-yl]carbamic acid, cyclohexyl ester, d ihydrochloride; (R)-7-Bromo-2,3 ,4,5-tetrahydro- 1 -methyl-I H-imidazol-5-yl)methyl)-4-(methylsulfonyl)-3- (phenylmethyl)- 1 H-i ,4-benzodiazepine, hydrochloride; (R)-7-Cyano-2,3,4,5-tetrahydro- 1 -methyl- I H-imidazol-5-yl)methyl]-4-(methylsulfonyl)-3- (phenylmethyl)- I H-i ,4-benzodiazepine, monohydrochloride; 4-[2-(4-Chlorophenyl)- 1 ,2-dioxoethy]-2,3,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-7phenyl- 1 H-I ,4-benzodiazepine, hydrochloride; 1,2-Dioxopropyl)-2,3,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-7-phenyl- 1 H- 1,4benzodiazepine, hydrochloride;, 2,3 ,4,5-Tetrahydro- I H-imidazol-4-ylmethyl)-4-[2-(4-nitrophenyl)- 1 ,2-dioxoethyl]-7-phenyl- I H-I ,4-benzodiazepine, hydrochloride; o 2,3 ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-4-[2-(4-methoxyphenyl)- 1 ,2-dioxoethyl]-7- 00 phenyl- I H-I ,4-benzodiazepine, hydrochloride; 2,3 ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-7-phenyl-4-(3 ,3,3 -trifluoro- 1 ,2-dioxopropyl)- 1 H-i ,4-benzodiazepine, trifluoroacetate (R)-7-Bromo-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylacetyl)-4-(methylsulfonyl)-3 (phenylmethyl)- 1 H-i ,4-benzodiazepine, monohydrochioride; IC (R)-7-Bromo-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylethyl)-4-(methylsulfonyl)-3- C) 10 (phenylmethyl)- I H-i ,4-benzodiazepine, monohydrochioride; 8-[(Cyclohexylcarbonyl)amino]- I ,2,3,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-3- (phenylmethyl)-4H- 1,4-benzodiazepine-4-carboxylic acid, methyl ester, dihydrochioride; N-[2,3 ,4,5-Tetrahydro- 1 I H-imidazol-4-ylmethyl)-4-( 1 -naphthalenylcarbonyl)- 1 H- 1,4benzodiazepin-8-yl]- 1 -piperidinecarboxamide, dihydrochioride; (R)-7-Cyano- 1,2,3 ,5-tetrahydro- 1 I H-imidazol-4-ylmethyl)-3-(phenylmethyl)-4H- 1,4benzodiazepine-4-carboxyl ic acid, ethyl ester, hydrochloride; N-[2,3 ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-4-(methylsulfonyl)-3 -(phenylmethyl)- I H- 1 ,4-benzodiazepin-8-yl]cyclohexanecarboxamide, di hydrochloride; (R)-7-Cyano-4-[[2-(dimethylamino)ethyl]sulfonyl]-2,3 ,4,5-tetrahydro- 1 H-imidazol-4ylmethyl)-3-(phenylmethyl)-4H-1 ,4-benzodiazepine, dihydrochloride; (R)-7-Cyano-2,3 ,4,5-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-4-[[2-(4morpholinyl)ethyl] sulfonyl] -3 -(phenylmethyl)-4H- 1,4-benzodiazepine, dihydrochloride; N-[2,3,4,5-Tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-4-(2-methoxy-3-methylbenzoyl)- IH- 1,4benzodiazepin8-yl]cyclohexanecarboxamide, dihydrochloride; 8-[(Cyclohexylcarbonyl)amino]-2,3,4,5-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-N-phenyl- IH- 1 ,4-benzodiazepine-4-carboxamide, dihydrochloride; N-[2,3 ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-4-[(2-methylphenyl)sulfonyl]- 1 H- 1,4benzodiazepin-8-yl]cyclohexanamide, dihydrochioride; N-[2,3 ,4,5-Tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-4-[(2-methoxyphenyl)carbonyl]- 1H- 1,4benzodiazepin-8-yl]cyclohexanamide, di hydrochiloride; (R)-7-Cyano-1I,2,3 ,5-tetrahydro- 1-(1 H-imidazol-4-ylmethyl)-3 -(phenylmethyl)-4H- 1,4benzodiazepine-4-sul fonic acid, ethyl ester, hydrochloride; (3 R)-7-Bromo-l1-[cyano( IH-imidazol-4-yl)methyl]-2,3,4,5-tetrahydro-4-(methylsulfonyl)-3 (phenylmethyl)- 1 H-I ,4-benzodiazepine, monohydrochloride; (3 I -[2-Amino- I H-imidazol-4-yl)ethyl]-2,3,4,5-tetrahydro4-(methylsulfonyl)-3- (phenylmethyl)-1IH-1 ,4-benzodiazepine, dihydrochioride; (3 I -[2-(Dimethylamino)- 1 H-imidazol-4-yi)ethyl]-2,3,4,5-tetrahydro-4-(methylsulfonyi)- 00 3 -(phenylmethyl)- 1 H-i ,4-benzodiazepine, dihydrochioride; 1 -[2-Amino- I H-imidazol-4-yl)ethyl]-7-bromo-2,3 ,4,5-tetrahydro-4-(methylsulfonyl)-3- (phenylmethyl)- I H-i ,4-benzodiazepine, dihydrochioride; I -[2-(Dimethylamino)- I H-imidazol-4-yl)ethyl]-7-bromo-2,3 ,4,5 -tetrahydro-4- (methylsulfonyl)-3 -(phenyimethyl)- I H-i ,4-benzodiazepine, dihydrochioride; 7-Cyano- 1,3 ,4,5-tetrahydro- I -methyl- I H-imidazoi-5-ylmethyl)-3 -(phenyl methyi)-4- C) 10 (phenylsulfonyl)-2H-1i,4-benzodiazepin-2-one, monohydrochioride; 7-Cyano- i ,3 ,4,5-tetrahydro- I H-imidazol-4-ylmethyl)-3 -(phenylmethyl)-4-(phenylsufonyl)- 2H-1i,4-benzodiazepin-2-one, monohydrochioride; 7-Bromo-2,3 ,4,5 -tetrahydro- I I H-imidazol-4-ylmethyi)-4-(methylsul fonyl)-3 -(2-phenylethyl)- IH-i ,4-benzodiazepine, dihydrochioride; 7-Bromo-3 -chilorophenyl)methyl] -2,3 ,4,5 -tetrahydro- 1 H-imidazol-4-ylmethyl)-4- (methylsuifonyl)- 1 H-i ,4-benzodiazepine, dihydrochioride; (R)-7-Bromo-3 -(cyclohexylmethyl)-2,3 ,4,5 -tetrahydro- I H-imidazol-4-yl methyl)-4- (methylsuifonyl)- I H-i ,4-benzodiazepine, dihydrochioride; 7-Bromo-3 -[(2-chlorophenyl)methyl] -2,3,4,5 -tetrahydro- I-(I H-imidazol-4-ylmethyl)-4- (methylsuifonyl)-l1H-i ,4-benzodiazepine, dihydrochioride; (S)-7-Bromo-3 -(cyclohexylmethyl)-2,3 ,4,5-tetrahydro- I I H-imidazol-4-ylmethyl)-4- (methylsul fonyl)- I H-i ,4-benzodiazepine, dihydrochioride; 7-Bromo-2,3,4,5 -tetrahydro- I I H-imidazol-4-ylmethyl)-3 -[(4-methoxyphenyl)methyl]-4- (methylsulfonyl)- I H-i ,4-benzodiazepine, dihydrochioride; 4-Acetyl-7-bromo-3-[(2-chiorophenyl)methyl]-2,3 ,4,5-tetrahydro- I I H-imidazol-4-ylmethyl)- IH-i ,4-benzodiazepine, dihydrochioride; 4-Acetyl-7-bromo-3-[(3-chlorophenyl)methyi]-2,3 ,4,5-tetrahydro- I I H-imidazoi-4-ylmethyl)- IH-i ,4-benzodiazepine, dihydrochioride; 7-Bromo-2,3,4,5-tetrahydro- I H-imidazol-4-ylmethyl)-3 -[(4-hydroxyphenyl)methyl]-4- (methylsulfonyl)- I H-i ,4-benzodiazepine, dihydrochioride; ,4,5-Tetrahydro- I I H-imidazol-4-ylmethyi)-4-(methylsulfonyl)-7-phenyl-3-(3pyridinylmethyl)- 1H-i ,4-benzodiazepine, di hydrochloride; 2,3,4,5-Tetrahydro-8-(hydroxymethyl)- I H-imidazoI-4-ylmethyl)-4-( 1naphthalenylcarbonyl)- I H-i ,4-benzodiazepine, dihydrochioride; 2,3 ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-4-( 1 -naphthalenylcarbonyl)-8- (phenoxymethyl)- I H-I ,4-benzodiazepine, dihydrochioride; o N-Cyclohexyi-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-4-( 1 -naphthalenylcarbonyl)- 1 H- C0 0 1 ,4-benzodiazepine-8-carboxamide, dihydrochioride; N-(Cyclohexylmethyl)-2,3 ,4,5-tetrahydro- 1 I H-imidazol-4-ylmethyl)-4-( 1naphthalenylcarbonyl)- 1 H-i ,4-benzodiazepine-8-carboxamide, dihydrochioride; 2,3,4,5 -Tetrahydro- 1 H-imidazol-4-ylmethyi)-4-( 1 -naphthalenylcarbonyl)-N-(phenyimethyl)- 1 H-I ,4-benzodiazepine-8-carboxamide, dihydrochioride; (R)-4-Acetyl-7-[2-[(dimethylamino)methyl]phenyl]-2,3 ,4,5-tetrahydro- 1 H-imidazol-4ylmethyl)-3-(phenylmethyl)- 1H-I ,4-benzodiazepine, dihydrochioride; (R)-4-Acetyl-7-cyano-2,3 ,4,5-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-3-(phenylmethyl)- IH- 1 ,4-benzodiazepine, monohydrochioride; (R)-7-Cyano-2,3 ,4,5-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-4-( I-oxobutyl)-3-(phenylmethyl)- I H-i ,4-benzodiazepine, monohydrochioride; (R)-7-Cyano-2,3 ,4,5-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-4-(2-methyl-l1-oxopropyl)-3- (phenylmethyl)- I H-i ,4-benzodiazepine, monohydrochioride; (R)-7-Cyano-2,3 ,4,5 -tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-3 -(phenylmethyl)-4-(2pyridinylacetyl)- 1 H-I ,4-benzodiazepine, di hydrochloride; (R)-7-Cyano-2,3,4,5 -tetrahydro-lI-(I H-imidazol-4-ylmethyl)-3 -(phenylmethyl)-4-(2thienylsulfonyl)- I H-I ,4-benzodiazepine, monohydrochioride; (R)-7-Cyano-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-4-[( 1 -methylethyl)sulfonyl]-3- (phenylmethyl)- 1 H-i ,4-benzodiazepine, monohydrochioride; (R)-7-Cyano-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-3-(phenylmethyl)-4- [(trifluoromethyl)sulfonyl] -1 H-i ,4-benzodiazepine, monohydrochioride; (R)-7-Bromo-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-3-(Phenylmethyl)-4- (propylsulfonyl)- 1 H-i ,4-benzodiazepine, monohydrochioride; (R)-7-Bromo-2,3,4,5-tetrahydro- I H-imidazol-4-ylmethyl)-3-(phenylmethyl)-4- (phenylsul fonyl)- 1H-i ,4-benzodiazepine, monohydrochioride; ,4,5 -Tetrahydro- 1 H-imidazol-4-ylmethyl)-7-phenyl-3 -(phenylmethyl)-4- (phenylsul fonyl)- 1 H-I ,4-benzodiazepine, monohydrochioride; ,4,5 -Tetrahydro- 1 H-imidazol-4-ylmethyl)-7-phenyl -3 -(phenyl methyl1)-4- (propylsulfonyl)- I H-I ,4-benzodiazepine, monohydrochioride; (R)-7-Cyano-4-[(4-fluorophenyl)sulfonyl]-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-3- (phenylmethyl)- I H-I ,4-benzodiazepine, monohydrochioride; (R)-7-Cyano-4-[(3-cyanophenyl)sulfonyl]-2,3,4,5-tetrahydro- 1 H-imidazol-4-yimethyl)-3- (phenylrnethyl)- 1 H-i ,4-benzodiazepine, monohydrochioride; o (R)-7-Cyano-2,3,4,5-tetrahydro- I H-imidazol-4-ylmethyl)-4-[( 1-methyl- I H-imidazol-2- 00 yl)sulfonyl]-3-(phenyimethyl)- 1H-I ,4-benzodiazepine, d ihydrochloride; (R)-4-[(3-Bromophenyl)sulfonyl]-7cyano-2,3 ,4,5-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-3- (phenylmethyl)- 1 H-i ,4-benzodiazepine, monohydrochioride; (R)-N-[5-[[7-cyano-2,3 ,4,5-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-3-(phenylmethyl)- IH- 1,4benzodiazepin-4-yl]sulfonyl]-4-methyl-2-thiazolyl]acetamide, dihydrochioride; 4-Acetyl-2,3 ,4,5-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-3-(phenylmethyl)-7-(4-pyridinyl)- 1H- C) 10 1 ,4-benzodiazepine, tri hydrochioride; 2,3,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-4-(2-phenyl-1I,2-dioxoethyl)-7-(4-pyridinyl)- I H-i ,4-benzodiazepine, tri hydrochloride; 2,3,4,5-Tetrahydro- I H-imidazol-4-ylmethyl)-7-(4-pyridinyl)-4-[2- (trifluoromethoxy)benzoyl] -1 H-I ,4-benzodiazepine, tri hydrochloride; (R)-2,3,4,5-Tetrahydro- 1I -(-methyl-i H-imidazol-5-yl)methyl]-4-(methylsulfonyl)-7-phenyl-3 (phenylmethyl)- 1 H-I ,4-benzodiazepine; (R)-7-Cyano-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-4-(Phenylacetyl)-3 (phenylmethyl)- 1 H-i ,4-benzodiazepine, monohydrochioride; 4-(2-Benzothiazolyl)-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-7-phenyl- 1 H- 1,4benzazepine, trihydrochioride; 2,3 ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-3-(phenylmethyl)-7-(3-pyridinyl)-4- (trifluoroacetyl)- I H-i ,4-benzodiazepine, tri hydrochloride; 2,3,4,5-Tetrahydro- 1 H-imidazoi-4-yimethyl)-4-(methyisulfonyl)-3-(phenylmethyl)-7-(3pyridinyl)- I H-i ,4-benzodiazepine, trihydrochioride; 7-Bromo-3-[( I -dimethylethoxy)methyl]- 1,2,3 ,4-tetrahydro- 1 1 ,4-benzodiazepin-Sone; 7-Bromo-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-4-(methylsulfonyl)-3 (phenoxymethyl)- 1 H-I ,4-benzodiazepine, dihydrochioride; 7-Bromo-2,3,4,5-tetrahydro-3-(hydroxymethyl)- 1 I H-imidazol-4-ylmethyl)-4- (methylsulfonyl)- 1 H-I ,4-benzodiazepine, monohydrochioride; 7-Bromo-3 -dimethylethoxy)methyl]-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-4- (methylsulfonyl)- I H-I ,4-benzodiazepine; [7-Bromo-2,3,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-3 -(phenylmethyl)- I H- 1,4benzodiazepin-8-yl]carbamic acid, 2-methyipropyl ester, trihydrochioride; [4-Acetyl-7-bromo-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-3 -(phenylmethyl)- 1 H- 1,4benzodiazepin-8-yI]carbamic acid, 2-methyipropyl ester; o N-[4-Acetyl-2,3 ,4,5-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-3-(phenylmethyl)- I H- 1,4- 00 benzodiazepin-8-yI]cyclohexanecarboxamide, dihydrochioride; [7-Bromo-2,3,4,5-tetrahydro- 1 H-imidazol-4-yimethyl)-4-(methylsulfonyl)-3 (phenylmethyl)- 1 H-I ,4-benzodiazepin-8-yi]carbamic acid, 2-methyipropyl ester; ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-4-(phenylsulfonyl)-3-(phenylmethyl)- I H- 1 ,4-benzodiazepine-7-carbonitriie, monohydrochioride; ID7-Bromo- 1,2,3 ,5-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-3 -(phenylmethyl)-4H- 1,4benzodiazepine-4-acetamide; 7-Bromo-4-[(dimethylamino)acetyl]-2,3,4,5-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-3- (phenylmethyl)- I H-I ,4-benzodiazepine; (R)-7-Bromo-4-(1I,2-dioxopropyi)-2,3 ,4,5-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-3- (phenylmethyl)- 1 H-i ,4-benzodiazepine, trifluoroacetate; (R)-7-Bromo-4-(cyclopropylcarbonyl)-2,3 ,4,5-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-3 (phenylmethyl)- I H-i ,4-benzodiazepine, trifluoroacetate; (R)-7-Cyano-2,3,4,5-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-3-(phenylmethyl)-4- (propylsulfonyl)- 1 H-i ,4-benzodiazepine, monohydrochioride; 7-Bromo-2,3 ,4,5-tetrahydro- 1,4-bis( 1H-imidazol-4-ylmethyl)-3-(phenylmethyl)- 1H- 1,4benzodiazepine, dihydrochioride; 7-Bromo- I ,2,3,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-N,N-dimethyl-3-(phenylmethyl)-4H- I ,4-benzodiazepine-4-sulfonamide, monohydrochioride; 2,3,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-4-(methylsulfonyl)-3-(phenylmethyl)- 1 H- 1,4benzodiazepine-7-carbonitri le, monohydrochioride; (R)-7-Cyano-1 ,2,3 ,5-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-N,N-dimethyl-3-(phenylmethyl)- 4H- 1,4-benzodiazepine-4-carboxamide monohydrochioride; N,N-Diethyl-2,3 ,4,5-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-4-(methylsulfonyl)-3 (phenylmethyl)- 1 H-i ,4-benzodiazepine-7-carboxamide, monohydrochioride; 2,3,4,5-Tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-7-phenyl-4-( I-phenyl- 1H-tetrazol-5-yl)- 1H- 1 ,4-benzodiazepine, monohydrochioride; (R)-7-Cyano-2,3 ,4,5-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-3 -(phenylmethyl)-4-(2pyrazi nylcarbonyl)-4H-1I,4-benzodiazepine, monohydrochioride; (R)-4-[7-Bromo-2,3 ,4,5-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-3-(phenylmethyl)-4H- 1,4benzodiazepin-4-yI]-4-oxobutanoic acid, methyl ester, monohydrochioride; (R)-7-Cyano-2,3 ,4,5 -tetrahydro- 1 H-imidazol-4-ylmethyi)-4-(4-morpholinocarbonyl)-3- (phenylmethyl)- I H-i ,4-benzodiazepine, monohydrochioride; o (R)-7-Cyano-2,3,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-3-(phenylmethyl)-4-[[2-(I1 00 pyrrolidinyl)ethyl]sulfonyl]- I H-i ,4-benzodiazepine, dihydrochioride;- (S)-2,3,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-4-(methylsulfonyl)-7-phenyl-3 pyridinylmethyl)- 1 H- I,4-benzodiazepine, dihydrochioride; (R)-2,3,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-7-phenyl-3-(3 -pyridinylmethyl)-4-(2thienylsulfonyl)- 1 H-I ,4-benzodiazepine, dihydrochioride; 1-10 ,4,5-Tetrahydro- I H-imidazol-4-yimethyl)-7-phenyl-4-(propylsulfonyl)-3-(3- C) 10 pyridinylmethyl)- I H-i ,4-benzodiazepine, monohydrochioride; (R)-7-Bromo-2,3,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-4-(methylsulfonyl)-3 pyridinylmethyl)- I H-i ,4-benzodiazepine, monohydrochioride; 2,3 ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-4-(methylsulfonyl)-3-(phenylmethyl)-7-(2pyrimidinyl)- 1 Hl-i ,4-benzodiazepine,dihydrochloride; (R)-7-Bromo-2,3,4,5-tetrahydro- I I H-imidazol-4-yimethyl)-3-(phenylmethyl)-4- [(trifluoromethyl)suifonyl]- IH-i ,4-benzodiazepine, monohydrochioride; (R)-2,3,4,5-Tetrahydro- I I H-imidazol-4-ylmethyl)-7-phenyi-3-(phenylmethyl)-4- (tri fluoroacetyl)- 1 H-i ,4-benzodiazepine, monohydrochioride; (R)-2,3,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-4-(methyisulfonyl)-3-(phenylmethyl)-7-(4pyridinyl)- I H-i ,4-benzodiazepine, dihydrochioride; (R)-2,3,4,5-Tetrahydro- 1 H-imidazol-4-yimethyi)-3-(phenylmethyl)-7-(4-pyridinyl)-4-(2thienylsulfonyl)- 1 H-i ,4-benzodiazepine, d ihydrochloride; (R)-2,3,4,5-Tetrahydro 1 H-imidazol-4-ylmethyi)-3-(phenylmethyl)-4-(phenyisufonyl)-7-(4pyridinyl)- I H-i ,4-benzodiazepine, dihydrochioride; (R)-2,3,4,5-Tetrahydro- I H-imidazol-4-ylmethyl)-3-(phenylmethyl)-4-(propylsulfonyl)-7-(4pyridinyl- 1 H-i ,4-benzodiazepine, dihydrochioride; (R)-7-Cyano-2,3 ,4,5-tetrahydro- I H-imidazol-4-ylmethyl)-3 -(phenylmethyl)-4-[(3,5dimethyl-isoxazoi-4-yI)sulfonyl]- I H-i ,4-benzodiazepine, dihydrochioride; (R)-7-Cyano4[(4-cyanophenyl)sulfonyl]-2,3,4,5-tetrahydro- I H-imidazol-4-ylmethyl)-3- (phenylmethyl)- I H-i ,4-benzodiazepine, dihydrochioride; (R)-7-Cyano-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-yimethyl)-3-(phenylmethyl)-4-[(2,2,2trifluoroethyl)sulfonyl]- I H-i ,4-benzodiazepine, di hydrochloride; (R)-[(5-Bromo-2-thienyl)sulfonyl]-7-cyano-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-3- (phenylmethyl)- 1 H-i ,4-benzodiazepine, dihydrochi~oride; (R)-7-Cyano-2,3 ,4,5 -tetrahydro- 1 H-imidazol-4-ylmethyl)-4-[(4-methoxyphenyl)sulfonyl]-3 (phenylmethyl)- 1 H-i ,4-benzodiazepine, dihydrochioride; oN-[[7-Bromo-2,3 ,4,5-tetrahydro- I H-imidazoi-4-ylmethyl)-4-(methylsulfonyl)- 1 H- 1,4- 00 benzodiazepin-3-ylmethyl]benzamide, dihydrochioride; (R)-7-Cyano- 1,2,3 ,5-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-N,N-dimethyl-3-(phenylmethyl)- 4H-1I,4-benzodiazepine-4-sulfonamide, hydrochloride; (R)-7-Cyano- 1,2,3 ,5-tetrahydro-N,N-dimethyi-l1-[(1-methyl-i H-imidazol-5-yl)methyl]-3- (phenylmethyl)-4H-1I,4-benzodiazepine-4-sulfonamide, hydrochloride; 1-10(R)-7-Chloro-2,3 ,4,5-tetrahydro-l1-[(1-methyl-i H-imidazol-5-yl)methyl]-4-(methylsulfonyl)-3- (phenyimethyl)- 1 H-i ,4-benzodiazepine, monohydrochioride; (R)-7-Chloro-2,3 ,4,5-tetrahydro- 1-(1 H-imidazol-4-ylmethyl)-4-(methylsulfonyl)-3 (phenylmethyl)- 1 H-i ,4-benzodiazepine, monohydrochioride; (R)-7-Chloro-2,3 ,4,5-tetrahydro-lI-[(1-methyl-i H-imidazol-5-yl)methyl]-4-(phenylsulfonyl)-3phenylmethyl)- I H-i ,4-benzodiazepine, monohydrochioride; (R)-7-Cyano-2,3 ,4,5-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-3 -(pyridin-3-ylmethyl)-4- (methylsulfonyl)- 1 H-I ,4-benzodiazepine, tetrahydrochioride; (R)-7-Bromo-2,3 ,4,5-tetrahydro- 1-(1 H-imidazol-2-ylmethyl)-4-(methylsulfonyl)-3 (phenylmethyl)- I H-i ,4-benzodiazepine, dihydrochioride; (R)-7-Bromo-2,3,4,5-tetrahydro-l1-(1 H-imidazoi-4-yimethyl)-4-[( 1-methyl-i H-imidazol-4yl)sulfonyl]-3-(phenyimethyl)- 1H-i ,4-benzodiazepine, trihydrochioride; (R)-7-Chloro-2,3 ,4,5-tetrahydro- I-(1 -methyl-imidazol-5-ylmethyl)-4-[(2-morpholin-4-yiethyl)sulfonyl]-3-(phenylmethyi)- 1 H-i ,4-benzodiazepine, dihydrochioride; (R)-7-Chloro-2,3 ,4,5-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-4-[(2-morpholin-4-yIethyl)sulfonyl]-3-(phenylmethyl)- 1H-i ,4-benzodiazepine, dihydrochioride; (R)-7-Chloro-4-[(dimethylamino)suifonyl]- I-[(1-methyl-i H-imidazol-5-yI)methyl]-3- (phenylmethyl)- 1 H-i ,4-benzodiazepine, monohydrochioride; (R)-7-Chloro-2,3 ,4,5-tetrahydro-l1-(1 -methyl-imidazol-5-yimethyl)-4-[(4-methyl-piperidin-4-yethyl)sulfonyl]-3-(phenylmethyl)- 1H-I ,4-benzodiazepine, dihydrochioride;, (R)-7-Bromo-2,3 ,4,5-tetrahydro- 1 -methyl-imidazol-5-ylmethyl)-4-[(4-methyl-piperidin-4-ylethyl)sulfonyl]-3-(phenylmethyl)- IH-i ,4-benzodiazepine, dihydrochioride; (R)-7-Cyano- 1,2,3 ,5-tetrahydro-lI-(1 H-imidazol-4-yimethyl)-3 -(phenylmethyl)-4H-1I,4benzodiazepine-4-carboxyl ic acid, isopropyl ester, hydrochloride; (R)-7-Bromo-2,3,4,5-tetrahydro-4-[[2-( IH-imidazol- 1-yl)ethyl]sulfonyl]- I-(1 H-imidazol-4ylmethyl)-3-(phenylmethyl)-1I H-i1,4-benzodiazepine, dihydrochioride; 88 (R)-7-Cyano-2,3 ,4,5-tetrahydro- I H-imidazol-4-ylmethyl)-4-(propylsulfonyl)-3 pyridinylmethyl)- I H-i ,4-benzodiazepine, hydrochloride; o 7-Bromo-2,3 ,4,5-tetrahydro- I H-imidazol-4-ylmethyl)-3 -(phenylmethyl)- 1 H- 1,4- 00 benzodiazepin-5-one, hydrochloride; (R)-7-Bromo-2,3 ,4,5-tetrahydro-l1-(1 H-imidazol-1I-ylacetyl)-4-(methylsulfonyl)-3 (phenylmethyl)- 1 H-i ,4-benzodiazepine, trifluoroacetate; 1 ,2,4,5-Tetrahydro-l1-(1 H-imidazoi-4-ylmethyl)-2-(2-phenylethyl)-3 H-i ,4-benzodiazepin-3one; 2,3 ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-4-(methylsulfonyl)-2-(2-phenylethyl)- 1 H- 1,4- C) 10 benzodiazepine, monohydrochioride; N(R)-2,3 ,4,5-Tetrahydro-l1-(1 H-imidazol-4-ylmethyi)-4-(methylsulfonyl)-7-phenyl-3-(4pyridinylmethyl)- 1 H-i ,4-benzodiazepine, dihydrochioride; ,4,5-Tetrahydro-l1-(1 H-irnidazol-2-ylmethyl)-4-(phenylsulfonyl)-3-(phenylmethyl)- 1H- 1 ,4-benzodiazepine-7-carbonitri le, hydrochloride; (R)-7-Cyano- 1,2,3,5-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-N,N-dimethyl-3-(3pyridinylmethyl)-4H- 1,4-benzodiazepine-4-carboxamide, dihydrochioride; (R)-7-Cyano- 1,2,3 ,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-N,N-dimethyl-3-(3pyridinylmethyl)-4H-1I,4-benzodiazepine-4-sulfonamide, dihydrochioride; ,4,5-Tetrahydro- 1 -(4cyanophenylmethyl)-imidazol-5ylmethyl)-4-(methylsul fonyl)-3 (phenylmethyl)- I H-I ,4-benzodiazepine-7-carbonitrile, hydrochloride; (R)-2,3,4,5-Tetrahydro- 1 -(4-cyanophenylmethyl)-imidazol-4-ylmethyl)-4-(methylsulfonyl)- 3phenylmethyl)- 1 H-i ,4-benzodiazepirie-7-carbonitrile, hydrochloride; (R)-4-IBenzoyl-7-Cyano-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-3-(phenylmethyl)- I H- 1 ,4-benzodiazepine, monohydrochioride; (R)-7-Cyano-2,3 ,4,5-tetrahydro-lI-[(1-methyl-i H-imidazol-5-yl)methyl]-3-(pyridin-3ylmethyl)-4-(methylsulfonyl)-1I H-i ,4-benzodiazepine, dihydrochioride; (R)-7-Cyano-2,3 ,4,5-tetrahydro-l1-[(i-methyl-i H-imidazol-5-yl)methyl]-3-(pyridin-3ylmethyl)-4-(propylsulfonyl)- 1 H-i ,4-benzodiazepine, trihydrochioride; (R)-7-Cyano-2,3,4,5-tetrahydro-l1-[(1 H-imidazol-4-yi)methyi]-3-(pyridin-3-ylmethyl)-4- (phenylsul fonyl)-1I H-i ,4-benzodiazepine, dihydrochioride; 2,3 ,4,5-Tetrahydro-l1-(1 H-imidazol-4-yimethyl)-4-(methylsulfonyl)-7-phenyi-3- (phenyimethyl)- 1 H-i ,4-benzodiazepine; 1,2,3 ,5-Tetrahydro- I H-imidazol-4-ylmethyl)-N-( 1 -naphthalenyl)-7-phenyl-4H- 1,4benzodiazepine-4-carboxamide, monohydrochioride; (S)-7-Bromo-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-4-(methylsulfonyl)-3 (phenylmethyl)- 1 H-i ,4-benzodiazepine, hydrochloride; o N-[2,3 ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-4-(2,3 -dimethylbenzoyl)- 1 H- 1,4- 00 benzodiazepin-8-yI] cyclohexanecarboxamide, dihydrochioride; (R)-7-Cyano-N-[2-(dimethylamino)ethyl]-2,3 ,4,5-tetrahydro- 1-(1 H-imidazol-4-ylmethyl)-Nmethyl-3-(phenylmethyl)- 1 H-I ,4-benzodiazepine-4-carboxamide, trifluoroacetate 7-Bromo-2,3,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-4-(methylsulfonyl)-2-oxo-3- (phenylmethyl)- 1 H-I ,4-benzodiazepine, trifluoroacetate; 1-10(R)-7-Cyano-4-(2-furanylcarbonyl)-2,3 ,4,5-tetrahydro- 1 I H-imidazol-4-ylmethyl)-3- (phenylmethyl)- 1 H-i ,4-benzodiazepine, trifluoroacetate 1); (R)-7-Cyano-2,3 ,4,5-tetrahydro- 1 I H-imidazol-4-ylmethyl)-4-[(4-nitrophenyl)sulfonyl]-3- (phenylmethyl)- I H-I ,4-benzodiazepine, trifluoroacetate; (R)-7-Cyano-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-4-[[4-(4-methyl- 1 piperazin)phenyl]sulfonyl]-3-(phenylmethyl)- 1 H-i ,4-benzodiazepine, trifluoroacetate; (R)-7-Cyano-2,3,4,5-tetrahydro- 1 I H-imidazol-4-ylmethyl)-4-[[(4dimethylamino)phenyl] sulfonyl] -3 -(phenylmethyl)- 1H-i ,4-benzodiazepine, trifluoroacetate; (R)-7-Bromo-4-[[2-(dimethylamino)ethyl]sulfonyl]-2,3,4,5-tetrahydro-l1-(1 H-imidazol-4ylmethyl)-3-(phenylmethyl)-4H-1 ,4-benzodiazepine, dihydrochioride; (R)-7-Cyano-2,3 ,4,5 -tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-3-(phenylmethyl)-4-(3pyridinylsulfonyl)- I H-i ,4-benzodiazepine, trihydrochioride; 2,3 ,4,5-Tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-4-(methylsulfonyl)-3-(phenylmethyl)- IH- 1,4benzo-diazepine, dihydrochioride; (R)-7-Bromo-2,3 ,4,5-tetrahydro- I-[(1-methyl-I H-imidazol-4-yl)methyl]-4-(methylsulfonyl)-3 (phenylmethyl)- 1 H-i ,4-benzodiazepine, di hydrochloride; (R)-4-[[3-(Dimethylamino)propyl]sulfonyl]-2,3 ,4,5-tetrahydro-1I-(I H-imidazol-4-ylmethyl)-7phenyl-3 -(phenylmethyl)- 1 H-I ,4-benzodiazepine, dihydrochioride; (R)-7-Cyano-2,3 ,4,5-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-3 -(phenylmethyl)- I H- 1,4benzodiazepine, tri hydrochloride; 4-Butyl-2,3 ,4,5-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-3-(Phenylmethyl)- I H- 1,4benzodiazepine, trihydrochloride; (R)-7-Bromo-2,3,4,5-tetrahydro-i-(I H-imidazol-4-ylmethyl)-4-[[2-(4morpholinyl)ethyl]sulfonyl]-3-(phenylmethyl)-l1H-i ,4-benzodiazepine, d ihydrochloride; (R)-7-Bromo-2,3 ,4,5-tetrahydro- I-[(1-methyl-i H-imidazol-5-yI)methyl]-4- morpholinyl)ethyl]sulfonyl]-3-(phenylmethyl)- 1 H-i ,4-benzodiazepine, dihydrochioride; (R)-7-Cyano- 1 H-imidazol-4-ylmethyl)-4-(4-morpholinylsulfonyl)-3-(phenylmethyl)- 1 H- 1,4- N_ benzodiazepine, monohydrochioride; o (R)-7-Cyano-I 1 [(-methyl-I H-imidazol-5-yl)methyl]-4-[(4-morpholinyl)sulfonyl-]-3- 00 (phenylmethyl)- IH-I ,4-benzodiazepine, monohydrochloride; (R)-7-Cyano-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-4-[(4-aminophenyl)sulfonyl]-3- (phenylmethyl)- IH-i ,4-benzodiazepine, hydrochloride; 1-10 2,3 ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-4-[(4-pyridylthio)acetyl]-7-phenyl- 1 H- 1,4benzodiazepine, dihydrochioride; 1-0N-(4-Chlorophenyl)-N'-cyano- 1,2,3 ,5-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-7-phenyl-4H- 1,4- C) 10 benzodiazepine-4-imidamide, monohydrochioride; 4-Acetyl-7-bromo- 1,2,4,5,1 ',3'-hexahydro-l1-(1 H-imidazol-4-ylmethyl)spiro[3H- 1,4benzodiazepine-3,2'-[2H]indene), dihydrochioride; 7-Bromo-4-[3-(dimethylamino)-l1-oxopropyl]-2,3 ,4,5-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)- 3-(phenylmethyl)- 1H-i ,4-benzodiazepine, trifluoroacetate 1); ,4,5-Tetrahydro-l1-(1-methyl-I H-imidazol-5-ylmethyl)-4-(phenylsulfonyl)-3- (phenylmethyl)- 1H-I ,4-benzodiazepine-7-carbonitri le, monohydrochioride; 2,3 ,4,5-Tetrahydro-l1-[(1-methyl-I H-imidazol-5-yl)-methyl]-4-(methyl-sulfonyl)-7-phenyl-3 (pyridin-3-yl-methyl)- 1 H-i ,4-benzodiazepine, hydrochloride trifluoroacetate (1:0.75) salt; 4-[4-(Fluorophenyl)sulfonyl]-2,3 ,4,5-tetrahydro- 1 H-imidazolI-4-yl methy l)-2 -(2-phenyl ethyl)- 1 H-i ,4-benzodiazepine, monohydrochloride; 7-Bromo-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-yl-methyl)-4-(methyl-sulfonyl)-2-(2phenylethyl)- 1 H-i ,4-benzodiazepine, monohydrochloride; (R)-7-Cyano-2,3 ,4,5-tetrahydro- 1 -methyl- I H-imidazol-5-ylmethyl)-4-[[2-( 1morpholinyl)ethyl]sulfonyl]-3 -(phenylmethyl)- 1H-I ,4-benzodiazepine, d ihydrochloride; (R)-7-Bromo-2,3,4,5-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-4-(methyl-sulforiyl)-3-(4bromophenylmethyl)- 1 H-i ,4-benzodiazepine, hydrochloride; (R)-7-Bromo-2,3,4,5-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-4-(methyl-sul fonyl)-3-(thiazol-4ylmethyl)- 1 H-I ,4-benzodiazepine, hydrochloride; (R)-7-Bromo-2,3,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-4-(propyl-sulfonyl)-3-(thiazol-4ylmethyl)- 1 H-i ,4-benzodiazepine, hydrochloride; (R)-7-Bromo-2,3,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-4-(propylsulfonyl)-3 bromophenylmethyl)- 1 H-I ,4-benzodiazepine, hydrochloride; (R)-7-Bromo-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-3 -(pyridin-3 -ylmethyl)-4- (methylsulfonyl)- 1 H-i ,4-benzodiazepine, trihydrochioride; o (R)-7-Bromo-2,3 ,4,5-tetrahydro- I H- I -methyl-imidazol-5-ylmethyl)-3-(pyridin-3-ylmethyl)- 00 4-(methylsulfonyl)- 1 H-I ,4-benzodiazepine, dihydrochloride; (R)-7-Cyano-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-4-(phenyl-sulfonyl)-3-(4cyanophenylmethyl)- 1 H-i ,4-benzodiazepine, hydrochloride; (R)-7-Cyano-4-[(N-methyl-N-phenylmethyl)aminosulfonyl]-I 1+I( H-imidazol-4-yl)methyl]-3- (phenylmethyl)- 1 H-i ,4-benzodiazepine, monohydrochioride; 1-10 (R)-7-Cyano4-[N-(tetrahydroisoquinoline)sulfonyl]- 1 H-imidazol-4-yl)methyl]-3- (phenylmethyl)- 1 H-i ,4-benzodiazepine, monohydrochioride; (R)-7-Cyano-2,3 ,4,5-tetrahydro- 1 -(1I H-imidazol-4-ylmethyl)-4-(phenylsulfonyl)-3-(2thienylmethyl)- 1 H-i ,4-benzodiazepine, hydrochloride; cis-2,3 ,4,5-Tetrahydro- 1 ,5-bis( 1 H-imidazol-4-ylmethyl)-3-(Phenylmethyl)- 1 H- benzodiazepine-2-carboxyl ic acid ethyl ester-trifluoroacetate (R)-7-Cyano4-[(N-piperidinyl)sulfonyl]- H-imidazol-4-yl)methyl]-3-(phenylmethyl)- 1 H- 1 ,4-benzodiazepine, monohydrochioride; (R)-7-Cyano-2,3,4,5-tetrahydro-l1-(1 H-i -methyl-imidazol-5-ylmethyl)-3 -(phenylmethyl)-4-(2thienylsulfonyl)- 1 H-I ,4-benzodiazepine, hydrochloride; (R)-7-Cyano-2,3 ,4,5-tetrahydro-l1-( IH-imidazol-4-ylmethyl)-3 -(pyridin-3-ylmethyl)-4-[[2- (dimethylaniino)ethyl]sulfonyl]- I H-i ,4-benzodiazepine, trihydrochioride; (R)-7-Cyano-2,3 ,4,5-tetrahydro-l1-( IH-i -methyl-imidazol-5-ylmethyl)-3-(phenylmethyl)-4- (propylsulfonyl)- 1 H-i ,4-benzodiazepine, hydrochloride; N-(Cyano)-N'-methyl- 1,2,3 ,5-tetrahydro-l1-( IH-imidazol-4-ylmethyl)-7-phenyl-4H- 1,4benzodiazepine-4-imidamide, hydrochloride; (R)-7-Cyano-4-[(2-nitrophenyl)-sulfonyl]-2,3,4,5-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-3- (phenyl-methyl)- 1 H-i ,4-benzodiazepine, hydrochloride; (R)-7-Cyano-4-[(4-methyl-phenyl)sulfonyl]-2,3,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-3- (phenylmethyl)- 1 H-I ,4-benzodiazepine, hydrochloride; (R)-7-Cyano4-(butylsulfonyl)-2,3,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-3 (phenylmethyl)- 1 Hl-i ,4-benzodiazepine, hydrochloride; (R)-7-Cyano-4-[(2-trifluoro-methylphenyi)sulfonyl]-2,3 ,4,5 -tetrahydro- 1I-(]I H-imidazol-4yI methyl)-3 -(phenylmethyl)- 1 H-I ,4-benzodiazepine, hydrochloride; (R)-7-Cyano-4-[(2-trifluoromethylphenyl)sulfonyl]-2,3 ,4,5-tetrahydro- 1 H-imidazol-4ylmethyl)-3-(phenylmethyl)-I H-i ,4-benzodiazepine, hydrochloride; (R)-7-Cyano-4-[(2-methoxy-carbonylphenyl)sulfonyl]-2,3,4,5-tetrahydro- I H-imidazol-4ylmethyl)-3-(phenylmethyl)- 1 H-i ,4-benzodiazepine, hydrochloride; o(R)-7-Cyano-4-[(2-methyl-sulfonylphenyl)sulfonyl]-2,3 ,4,5-tetrahydro- I -mdzl4 00 ylmethyl)-3-(phenylmethyl)- 1 H-i ,4-benzodiazepine, hydrochloride; (R)-7-Cyano-2,3,4,5-tetrahydro- 1 H-imidazot-4-ylmethyl)-3-(phenylmethyl)-4-(((4methylnonyl)-phenyl)-sulfonyl)- I H-I ,4-benzodiazepine; (R)-7-Cyano-2,3,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-3-(phenylmethyl)-4-(((4trifluoromethyl)-phenyl)-sulfonyl)- 1 H-i ,4-benzodiazepine; (R)-7-Cyano-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-yimethyl)-3-(phenylmethyl)-4-((3 C) 10 methoxypropyl)-sulfonyl)- 1 H-I ,4-benzodiazepine; (R)-7-Cyano-2,3 ,4,5-tetrahydro- 1 I H-imidazol-4-ylmethyl)-3-(phenylmethyl)-4-((3,4dimethoxyphenyl)-sulfonyl)- 1 H-I ,4-benzodiazepine; (R)-7-Cyano-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-3-((4-fluorophenyl)methyl)-4- (phenylsulfonyl)- I H-I ,4-benzodiazepine; (R)-7-Cyano-4-(N-cyclopropylmethyl-N-propyl)-aminosulfonyl]- I H-imidazol-4yl)methyl]-3-(phenylmethyl)- I H-I ,4-benzodiazepine; (R)-7-Cyano-4-[(N,N-(dibutylamino))-sulfonyl]- I H-imidazol-4-yI)methyl]-3- (phenylmethyl)- I H-i ,4-benzodiazepine; (R)-7-Chloro-4-(methanesulfonyl)-2,3,4,5 -tetrahydro- 1 H-imidazol-4-yl methyl)-3 (phenylmethyl)- 1 H-pyrido[3,4-e]- 1 ,4-diazepine; 1,2,3 ,4-Tetrahydro-7-bromo-4-[( 1 H-imidazol-4-yl)methyl]-2-phenylmethyl- 1 (methylsulfonyl)quinoxaline; (R)-7-Cyano-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-3-(phenylmethyl)-4-((imidazol-4yl)methylsulfonyl)- 1 H-I ,4-benzodiazepine; (R)-7-Cyano-2,3 ,4,5-tetrahydro- 1 I H-imidazol-4-ylmethyl)-3-((2-thienyl)methyl)-4- (propylsulfonyl)- I H-I ,4-benzodiazepine; (R)-7-Cyano-2,3 ,4,5 -tetrahydro- 1 H-imidazol-4-ylmethyl)-3 -((2-thienyl)methyl)-4-((2thienyl)-sulfonyl)- I H-i ,4-benzodiazepine; (R)-7-Cyano-2,3,4,5-tetrahydro- I H-imidazol-4-ylmethyl)-3-(phenylmethyl)-4-((3 methylthiopropyl)-sulfonyl)- 1 H-i ,4-benzodiazepine; (R)-7-Cyano-2,3,4,5-tetrahydro- I H-imidazoi-4-ylmethyl)-3-(phenylmethyl)-4-(((3methylthioxo)-propyl)-sulfonyl)- 1 H-i ,4-benzodiazepine; (R)-7-Cyano-2,3,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-3-(phenylmethyl)-4-(((3methylsulfonyl)-propyl)-sulfonyl)- 11H-i ,4-benzodiazepine; (R)-7-Cyano-2,3,4,5-tetrahydro-1I -(I1H-imidazol-4-ylmethyl)-3-(phenylmethyl)-4-((2- __methylpropyl)-sulfonyl)-1I H-I ,4-benzodiazepine; o (R)-7-Cyano-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-3 -(phenylmethyl)-4- 00 (cyclopentylsulfonyl)- I H-i ,4-benzodiazepine; (R)-7-Cyano-2,3,4,5-tetrahydro-1I -(I1H-imidazol-4-ylmethyl)-3-(phenylmethyl)-4-((4,4,4trifluorobutyl)-sulfonyl)- 1 H-i ,4-benzodiazepine; (R)-7-Cyano-2,3 ,4,5-tetrahydro- I H-imidazoi-4-ylmethyl)-3-(Phenylmethyl)-4- ((phenylmethyl)-sulfonyl)- 1 H-I ,4-benzodiazepine; N (R)-7-Cyano-2,3 ,4,5-tetrahydro- I H-imidazol-4-ylmethyl)-3 -(phenylmethyl)-4-[[2-(5-(N- C) 10 benzoyl)-aminomethyl)-thienyl]-sulfonyl]- 1 H-i ,4-benzodiazepine; (R)-7-Cyano-2,3,4,5-tetrahydro- I H-imidazol-4-ylmethyl)-3-(phenylmethyl)-4-[[2-( -1 chloro-5-methyl-pyridin-2-yl))-pyrrolyl]-sulfonyl]- I H-I ,4-benzodiazepine; (R)-7-Cyano-2,3 ,4,5-tetrahydro- 1 I H-imidazol-4-ylmethyl)-3-(phenylmethyl)-4-((4carboxyphenyl)-sulfonyl)- I H-i ,4-benzodiazepine; (R)-7-Cyano-2,3 ,4,5-tetrahydro- I H-imidazol-4-ylmethyl)-3 -(phenylmethyl)-4-[((3-methyl- 1 ,2,4-oxadiazol-5-yI)-phenyl)-sulfonyl]- 1 H-I ,4-benzodiazepine; (R)-7-Cyano-2,3,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-3 -(phenylmethyl)-4-((2,5dimethoxyphenyl)-sulfonyl)- 1 H-i ,4-benzodiazepine; (R)-7-Cyano-4-[(N-tetrahydroquinolinyl)sulfonyl]- I H-imidazol-4-yI)methyl]-3 (phenylmethyl)- I H-I ,4-benzodiazepine; (R)-7-Cyano-4-(N,N-bis-[ I -(2-methylpropyl)amino]-sulfonyl]- 1 H-imidazol-4-yI)methyl]-3- )phenylmethyl)- I H-i ,4-benzodiazepine; (R)-7-Cyano-4-[(N-methyl-N-phenyl)aminosulfonyl]- I H-imidazol-4-yl)methyl]-3- (phenylmethyl)- I H-I ,4-benzodiazepine; (R)-7-Cyano-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-3-(2-(2,6-dimethylphenyl)-ethyl)- 4-(methylsulfonyl)- 1 H-i ,4-benzodiazepine; (R)-7-Cyano-2,3 ,4,5-tetrahydro- 1 -(N-phthalimidoethyl)-imidazol-5-ylmethyl)-3- (phenylmethyl)-4-methylsulfonyl)- 1 H-I ,4-benzodiazepine; (R)-7-Cyano-2,3 ,4,5 -tetrahydro- 1 -[(2-(N,N-dimethylamino)-ethyl)-imidazol-5-ylmethyl]-3- (phenylmethyl)-4-(methylsulfonyl)- 1 H-I ,4-benzodiazepine; (R)-7-Cyano-2,3 ,4,5-tetrahydro- 1 -[(2-aminoethyl)-imidazol-5-ylmethyl]-3-(phenylmethyl)-4- (methylsulfonyl)- 1 H-i ,4-benzodiazepine; (R)-7-Bromo-4-(methanesulfonyl)-2,3 ,4,5-tetrahydro- I H-imidazol-4-ylmethyl)-3 (phenylmethyl)- 1 H-thieno[2,3-e]- 1 ,4-diazepine; (R)-7-Bromo-4-(methanesulfonyl)-2,3 ,4,5-tetrahydro- I H-imidazol-4-ylmethyl)-3- (phenylmethyl)-1I H-thieno[3,2-e]- 1,4-diazepine; (R)-4-(methanesulfonyl)-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-3-(phenylmethyl)- 1 H- 00 8-oxo-pyrimidino[4,5-e]- 1 ,4-diazepine; (R)-7-Cyano-2,3,4,5-tetrahydro-1I H-imidazol-4-ylmethyl)-3-((4-(2-methoxyethoxy)phenyl)methyl)-4-(phenylsulfonyl)- 1 H-i ,4-benzodiazepine; (R)-7-Cyano-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-3-((4-(2-(dimethylamino)-ethoxy)phenyl)methyl)-4-(phenylsulfonyl)- 1 H-I ,4-benzodiazepine; (R)-7-Cyano-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylsulfonyl)-3-(phenylmethyl)-4- C) 10 (methylsulfonyl)- 1 H-i ,4-benzodiazepine; (R)-7-Cyano-2,3,4,5-tetrahydro- 1 H-imidazol-4-ylsulfonyl)-3-(phenylmethyl)-4- (propylsulfonyl)- 1 H-i ,4-benzodiazepine; (R)-7-Cyano-2,3,4,5-tetrahydro- 1 H-imidazol-4-ylsulfonyl)-3-(phenylmethyl)-4- (phenylsulfonyl)-1I H-I ,4-benzodiazepine; (R)-7-Cyano-2,3 ,4,5-tetrahydro- I H-imidazol-4-ylsulfonyl)-3-(phenylmethyl)-4-(2thienylsulfonyl)-1I H-I ,4-benzodiazepine; 7-Cyano-2,3 ,4,5-tetrahydro- 1 I H-imidazol-4ylmethyl)-3-(R)-[(R)- 1 -phenylI-ethyl]-4- (methylsulfonyl)- 1 H-i ,4-benzodiazepine; 7-Cyano-2,3,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-3-(R)-[(R)- 1 -phenyl -ethyl] -4- (propylsulfonyl)- 1 H-i ,4-benzodiazepine; 7-Cyano-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-3 1 -phenyl-ethyl]-4- (phenyisulfonyl)-1I H-I ,4-benzodiazepine; 7-Cyano-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-3-(R)-[(R)- 1 -phenylI-ethyl] thienyl)-sulfonyl)- I H-i ,4-benzodiazepine; 7-Cyano-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-3-(S)-[(R)- 1 -phenyl-ethyl]-4- (methylsulfonyl)- 1 H-i ,4-benzodiazepine; 7-Cyano-2,3,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-3-(S)-[(R)- 1 -phenylI-ethyl] -4- (propysufonyl)- 1 H-i ,4-benzodiazepine; 7-Cyano-2,3,4,5-tetrahydro- 1 H-iniidazol-4-ylmethyl)-3-(S)-[(R)- 1 -phenyl-ethyl]-4- (phenylsulfonyl)- 1 H-i ,4-benzodiazepine; 7-Cyano-2,3 ,4,5-tetrahydro- I H-imidazol-4-ylmethyl)-3-(S)-[(R)- 1 -phenyl -ethyl] thienyl)-sulfonyl)- 1 H-i ,4-benzodiazepine; 7-Cyano-2,3,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-3-(R)-[(S)- I -phenyl-ethyl]-4- (methylsulfonyl)- I H-I ,4-benzodiazepine; 7-Cyano-2,3 ,4,5-tetrahydro- 1 H-imidazoi-4-ylmethyl)-3-(R)-[(S)- I -phenyl -ethyl] -4- (propylsuifonyl)- I H-i ,4-benzodiazepine; o 7-Cyano-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-3-(R)-[(S)- 1 -phenyl -ethyl] -4- 00 (phenylsulfonyl)- 1 H-i ,4-benzodiazepine; 7-Cyano-2,3,4,5-tetrahydro- I H-imidazol-4-ylmethyl)-3-(R)-[(S)- 1 -phenyl -ethyl] thienyl)-sulfonyl)- I H-I ,4-benzodiazepine; 7-Cyano-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-3-(S)-[(S)- I -pheny I-ethyl]-4- (methylsulfonyl)- 1 H-I ,4-benzodiazepine; 7-Cyano-2,3,4,5-tetrahydro- I H-imidazol-4-ylmethyl)-3-(S)-[(S)- 1 -phenyl-ethyl]-4- C) 10 (propylsulfonyl)- 1 H-I ,4-benzodiazepine; 7-Cyano-2,3,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-3-(S)-[(S)-1I -phenyl -ethyl] -4- (phenylsulfonyl)- I H-i ,4-benzodiazepine; 7-Cyano-2,3,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-3-(S)-[(S)- I -pheny I-ethyl] thienyl)-sulfonyl)- 1 H-i ,4-benzodiazepine; 7-Cyano-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-3-(R)-[(R)-phenylcyclopropyl)-4- (methylsulfonyl)- I Hl-i ,4-benzodiazepine; 7-Cyano-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-3-(R)-[(R)-phenylcyclopropyl)-4propylsulfonyl)- 1 H-i ,4-benzodiazepine; 7-Cyano-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-3-(R)-[(R)-phenylcyclopropyl)-4phenylsulfonyl)-1I H-I ,4-benzodiazepine; 7-Cyano-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-3-(R)-[(R)-phenylcyclopropyl)-4-((2thienyl)-sulfonyl)- 1 H-i ,4-benzodiazepine; 7-Cyano-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-3-(R)-[(S)-phenylcyclopropyl)-4- (methylsulfonyl)-1I H-i ,4-benzodiazepine; 7-Cyano-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-3-(R)-[(S)-phenylcyclopropyl)-4propylsulfonyl)- 1 H-i ,4-benzodiazepine; 7-Cyano-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-3-(R)-[(S)-phenylcyclopropyl)-4phenylsulfonyl)- 1 H-i ,4-benzodiazepine; 7-Cyano-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-3-(R)-[(S)-phenylcyclopropyl)-4-((2thienyl)-sulfonyl)- I H-i ,4-benzodiazepine; 7-Cyario-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-3-(S)-[(R)-phenylcyclopropyl)-4- (methylsulfonyl)- 1 H-i ,4-benzodiazepine; 7-Cyano-2,3,4,5-tetrahydro- I I H-imidazol-4-ylmethyl)-3-(S)-[(R)-phenylcyclopropyl)-4- (propylsulfonyl)- I H-I ,4-benzodiazepine; 7-Cyano-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-yimethyl)-3-(S)-[(R)-phenylcyclopropyl)-4- (phenyisulfonyl)- 1 H-I ,4-benzodiazepine; o 7-Cyano-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-3-(S)-[(R)-phenylcyclopropyl)-4-((2- 00 thienyi)-suifonyl)- 1 H-I ,4-benzodiazepine; 7-Cyano-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyi)-3-(S)-[(S)-phenylcyclopropyl)-4- (methylsulfonyl)- 1 H-i ,4-benzodiazepine; 7-Cyano-2,3,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-3-(S)-[(S)-phenylcyclopropyl)-4- (propylsulfonyl)-1I H-i ,4-benzodiazepine; 7-Cyano-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-3-(S)-[(S)-phenylcyclopropyl)-4- (phenylsulfonyl)- 1 H-I ,4-benzodiazepine; 7-Cyano-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-3-(S)-[(S)-phenylcyclopropyl)-4-((2thienyl)-sulfonyl)- 1 H-I ,4-benzodiazepine; (R)-7-Cyano-2,3 ,4,5-tetrahydro- 1 I H-imidazol-4-yimethyl)-3 -(phenylmethyl)-4-[(2-(5- (pyridin-2-yl))-thienyl)-sulfonyl])- I H-i ,4-benzodiazepine; 1 5 (R)-7-Cyano-2,3 ,4,5-tetrahydro- 1 H-imidazoi-4-ylmethyi)-3-(phenylmethyl)-4-[(2-(5-(- 1,2isoxazol-3-yl))-thienyl)-sulfonyl])- 1 H-i ,4-benzodiazepine; (R)-7-Cyano-2,3,4,5-tetrahydro- 1 H-imidazol-2-yi)-propyl)-3-(phenylmethyl)-4- (phenylsulfonyl)- I H-i ,4-benzodiazepine; (R)-7-Cyano-2,3 ,4,5-tetrahydro- 1 H-imidazol-2-yI)-propyl)-3-(phenylmethyl)-4- (methylsulfonyl)- I H-i ,4-benzodiazepine; (R)-7-Cyano-2,3 ,4,5-tetrahydro- 1 H-imidazoi-2-yl)-propyl)-3-(phenyimethyl)-4- (propylsulfonyl)- 1 H-i ,4-benzodiazepine; (R)-7-Cyano-2,3 ,4,5-tetrahydro- 1 H-imidazol-2-yi)-propyi)-3-(phenylmethyl)-4-((2thienyl)-sulfonyl)- 1 H-i ,4-benzodiazepine; (R)-7-Cyano-2,3 ,4,5-tetrahydro- 1 H-imidazoi-2-yl)-ethylsulfonyl)-3-(phenylmethyl)-4- (phenyisulfonyl)- I H-i ,4-benzodiazepine; (R)-7-Cyano-2,3 ,4,5-tetrahydro- 1 H-imidazol-2-yl)-ethylsulfonyl)-3-(phenylmethyl-4- (methylsulfonyl)- I H-i ,4-benzodiazepine; (R)-7-Cyano-2,3 ,4,5-tetrahydro- I H-imidazol-2-yi)-ethylsuifonyl)-3-(phenylmethyl)-4- (propylsulfonyl)- 1 H-i ,4-benzodiazepine; (R)-7-Cyano-2,3 ,4,5-tetrahydro- 1 H-imidazol-2-yl)ethylsulfonyl)-3-(phenylmethyl)-4-((2thienyl)-sulfonyl)- 1 H-i ,4-benzodiazepine; (R)-7-Cyano-2,3,4,5-tetrahydro- 1 H-imidazol-4-yimethyl)-3 -(phenylmethyl)-4-(( I -oxoethyl)amino)- 1 H-i ,4-benzodiazepine; 0 (R)-7-Cyano-2,3,4,5-tetrahydro- 1-(l H-imidazol-4-ylmethyl)-3-(phenylmethyl)-4- (methanesulfonylamino)- 1 H- ,4-benzodiazepine; and O (R)-7-Cyano-2,3,4,5-tetrahydro-l-(1H-imidazol-4-ylmethyl)-3-(phenylmethyl)-4- 00 (phenylsulfonylamino)- H- 1,4-benzodiazepine.

In one aspect of the invention is a method of treating a synucleinopathic subject, the method comprising, administering to a synucleinopathic subject a farnesyl transferase inhibitor Scompound of the formula: 0 R3 R Z1N iR2

N-

N

(CH2)n

R

4 or a stereoisomeric form, or a pharmaceutically acceptable acid or base addition salt form thereof, in a therapeutically effective amount, wherein R, is Cl, Br, CN, optionally substituted phenyl, or optionally substituted or 4-pyridyl; R 2 is optionally substituted lower alkyl, or optionally substituted aralkyl; R 3 and R 5 are each independently optionally substituted lower alkyl, optionally substituted aryl, or optionally substituted heterocyclo; R4 is hydrogen or lower alkyl; ZI is CO, SO 2

CO

2 or SO 2 and n is 1 or 2. In one embodiment the compound of the invention has the following substituents: RI is Br, or CN;

R

2 is optionally substituted benzyl;

R

3 is optionally substituted lower alkyl, optionally substituted phenyl, optionally substituted 2-thienyl, or optionally substituted 1-piperidinyl; R4 is hydrogen, or methyl; ZI is CO, SO 2 or SO 2

R

5 is optionally substituted lower alkyl or optionally substituted phenyl; and n is 1.

In yet another embodiment the compound of the invention has the following substituents: 00 R 2 is optionally substituted benzyl;

R

3 is optionally substituted lower alkyl, optionally substituted phenyl, optionally substituted 2-thienyl, or optionally substituted I1-piperidinyl;

R

4 is hydrogen, or methyl; Z is CO, or SO 2 and IND n isi1.

C) 10 In yet another embodiment the compound of the invention has the following substituents: R, is CN;

R

2 is benzyl;

R

3 is n-propyl, n-butyl, 3-methoxypropyl, 2-thienyl, 5-bromo-2-thienyl, phenyl, 4methoxyphenyl, or I -piperidinyl;

R

4 is hydrogen; Z is S02 and n is 1.

In yet another embodiment the compound of the invention is selected from the group consisting of: (R)-2,3,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-3-(phenylmethyl)-4-(2-thienylsulfonyl)- I H- I ,4-benzodiazepine-7-carbonitrile; (R)-7-cyano-2,3,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-4-( I -oxobutyl)-3-(phenylmethyl)- 1 H- 1 ,4-benzodiazepine; (R)-4-[(5-bromo-2-thienyl)sulfonyl]-7-cyano-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-yl methyl)- 3 -(phenyl methyl)-1I H-I ,4-benzodiazepine; (R)-7-cyano-2,3 ,4,5-tetrahydro-l1-(1 H-imidazol-4-yl methyl)-4-[(4-methoxyphenyl)sulfonyl]-3- (phenylmethyl)- 1 H-i ,4-benzodiazepine; (R)-7-cyano-2,3 ,4,5-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-3-(phenyl methyl)-4- (phenylsulfonyl)- 1 H-I ,4-benzodiazepine; (R)-7-cyano-2,3,4,5-tetrahydro- I H-imidazol-4-ylmethyl)-3-(~phenylmethyl)-4- (propylsulfonyl)-1I H-i ,4-benzodiazepine; (R)-4-(butylsulfonyl)-7-cyano-2,3,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-3- __(phenylmethyl)- 1 H-i ,4-benzodiazepine; o (R)-7-cyano-2,3,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-3-(phenylmethyl)-4-( 1- 00 piperidinylsulfonyl)- 1 H-i ,4-benzodiazepine; -methoxypropylsulfonyl)-7-cyano-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-3- (phenylmethyl)- I H-I ,4-benzodiazepine; and pharmaceutically acceptable salts thereof.

In certain embodiments of the invention the pharmaceutically acceptable salt is selected IND from the group consisting of the hydrochloride salt, the methanesulfonic acid salt and the trifluoroacetic acid salt.

In one embodiment of the invention compound of the invention is tetrahydro- 1 H-imidazol-4-ylmethyl)-3-(phenylmethyl)-4-(2-thienylsulfonyl)- I H- 1,4benzodiazepine-7-carbonitrile.

In another embodiment, the invention is a method of treating a synucleinopathic subject, the method comprising, administering to a synucleinopathic subject a famnesyl transferase inhibitor compound of the formula:

R

7

R

8 N-1 N 1 5 Rr-SsTt-Y/

R

1

R

2

R

3

R

4

R

5

R

6

R

9

R

10

P

SB C

\D

0

R

7

R

8 R R R R 6

O

RrSs--Y-R 1 M N S

N-

N

R

9

R

10 or a stereoisomeric form, or a pharmaceutically acceptable acid or base addition salt form thereof, in a therapeutically effective amount, wherein 1, m, r, s and t are 0 or 1; n is 0, 1 or 2; Y is selected from the group consisting of CHR' 2 SO2, SO 3 CO, C0 2 O, NR 1 3

SO

2

NR

4

CONR'

1 C(NCN), C(NCN)NR 1 6

NR

1 7 CO, NR' 8 SO2, CONR 9

NR

20

SO

2

NR

21

NR

22

S(O)(NR

23

S(NR

24

)(NR

25 or without Y; Z is selected from the group consisting of CR' 2

S,

SO, SO 2 S03, CO, C0 2 O, NR 1 3

SO

2

NR

1 4

CONR'

1

NR

26

NR

27

ONR

28

NR

29 O, NR 30

SO

2

NR

31

NR

32 S02, NR 33 C(NCN), NR 34

C(NCN)NR

3 5

NR

36 CO, NR 37

CONR

38

NR

39 C0 2

OCONR

4 0

S(O)(NR

4 1

S(NR

42

)(NR

43 or CHR 1 2 or without Z; R 7

R

8 are selected from the group consisting of hydrogen, halo, nitro, cyano and U-R44; U is selected from the group consisting of S, O, NR 45 CO, SO, SO 2

CO

2

NR

4 6 C0 2

NR

4 7

CONR

48

NR

49

SO

2

NR

5 0

SO

2

NR

51 SO2 NR 52

NR

53 CO, CONR 5 4

PO

2

R

5 5 and PO 3

R

56 or without U; R 9 Ro 1 R 2

R

1 3

R

1 4

R

1 5

R

1 6

R

1 7

R

1 8

R

1 9

R

20

R

2 1

R

22

R

23

R

2 4

R

25

R

26

R

27

R

28

R

29

R

3 0

R

31

R

32

R

33

R

34

R

35

R

36

R

37

R

38

R

39

R

40

R

1

R

42

R

43

R

45

R

46

R

47

R

48

R

49

R

5 S, R 5

R

5 2

R

3

R

54

R

55

R

5 6

R

57

R

58 and R 59 are selected from the group consisting of hydrogen, lower alkyl, aryl, heterocyclo, substituted alkyl or aryl or substituted hetercyclo; R 1 and R 44 are selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, aralkyl, cycloalkyl, aryl, substituted aryl, heterocyclo, substituted heterocyclo; R 2

R

3

R

4

R

5 and R 6 are selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, aralkyl, cycloalkyl, aryl, substituted aryl, heterocyclo, substituted heterocyclo, cyano, carboxy, carbamyl (e.g.

CONH

2 substituted carbamyl (where nitrogen may be substituted by groups selected from hydrogen, alkyl, substituted alkyl, aryl or aralkyl, substituted aryl, heterocyclo, substituted

ID

heterocyclo), alkoxycarbonyl; any two of R 2

R

3

R

4

R

5 and R 6 can join to form a cycloalkyl S group; any two of R 2

R

3

R

4

R

5 and R 6 together can be oxo, except when the carbon atom O bearing the substituent is part of a double bond; R, S and T are selected from the group 00 consisting of CH 2 CO and CH(CH 2 )p Q wherein Q is NR 57

R

58

OR

59 or CN; and p is 0, 1 or 2; A, B and C are carbon, oxygen, sulfur or nitrogen; D is carbon, oxygen, sulfur or nitrogen or without D; and with the provisos: 1. When I and m are both 0, n is not 0; c 2. R" may be hydrogen except when Z is SO, or when Z is O, NR' 3 or S and the carbon IN to which it is attached is part of a double bond or when Y is SO 2 CO2, NR 18 SO2,

S(O)(NR

23 or S(NR24)(NR25 3. R 44 may be hydrogen except when U is SO, SO 2

NR

46

CO

2 or NR 49

SO

2 In one embodiment the compound has the formula:

R

8 7

,R

B\m (i 2 Z- R 1

N-

RrSs Tt Y/ R 1

R

2

R

3

R

4

R

5

R

6 N R-Ss-T-t Y

N

R

9

R

10 wherein r, s and t are 0 or 1; 1 is 0; m is 1; n is 1; Y is selected from the group consisting of CHR' 2 SO2, SO 3 C0 2 O, NR 13

SO

2

NR

1 4

CONR'

1 C(NCN), C(NCN)NR 6

NR

7 CO, NR 1 8

SO

2

CONR

1 9

NR

20

SO

2

NR

21

NR

22 S(O)(NR23), S(NR 24

)(NR

2 5 or without Y; Z is selected from the group consisting of S, SO, SO2, SO3, CO, C0 2 O, NR 1 3

SO

2

NR

1 4

CONR

15

NR

26

NR

27

ONR

28

NR

29 0, NR 30 SO2 NR 3

NR

32

SO

2

NR

33 C(NCN), NR 34

C(NCN)NR

35

NR

36 CO, NR 37

CONR

38

NR

39

CO

2

OCONR

40

S(O)(NR

41 or S(NR42)(NR43); o R 7

R

8 are selected from the group consisting of hydrogen, halo, nitro, cyano and U-R 44 00 U is selected from the group consisting of S, O, NR 45 CO, SO, SO2, CO2, NR 46

CO

2

NR

4 7

CONR

48

NR

49 S02, NR 5 S SO 2 NR', SO2 NR 52

NR

53 CO, CONR 4 PO2 R 55 and PO3 R 56 or without U; O R9, R10 R2, R3, R14, RS, R6, R 1 7 R1, R19, R20 R21 R22 R23 R24 R25 R26 R27 R28 R29 D R30, R R32 R R3 R34, R R36, R37, R3, R39, R40, R41, R42, R43, R4, R R46 R47, R48, 49, RS 31 32 33 34 35 36 37 38 39 40 41 43 45 46 47 48 49 R ,R ,R ,R ,R ,R ,R ,R ,R ,R ,R ,R ,R R ,R ,R R, R 50

SR

51 R R 2

R

53

R

54

R

5 5

R

6

R

5 7

R

5 8 and R 59 are selected from the group consisting of

O

0 10 hydrogen, lower alkyl, aryl, heterocyclo, substituted alkyl or aryl; R" and R 44 are selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, aralkyl, cycloalkyl, aryl, substituted aryl, heterocyclo, substituted heterocyclo;

R

2

R

3

R

4

R

5 and R 6 are selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, aralkyl, cycloalkyl, aryl, substituted aryl, heterocyclo, substituted heterocyclo, cyano, alkoxycarbonyl, carboxy, carbamyl, substituted carbamyl wherein substituents on the nitrogen of the substituted carbamyl are selected hydrogen, alkyl, substituted alkyl, aryl or aralkyl, substituted aryl, heterocyclo, substituted heterocyclo; any two of R 2

R

3

R

4

R

and R 6 can join to form a cycloalkyl group; any two of R 2

R

3

R

4

R

5 and R 6 together can be oxo, except when the carbon atom bearing the substituent is part of a double bond; R, S and T are selected from the group consisting of CH 2 and CH(CH 2 )p Q wherein Q is

NR

57 Rs, OR 59 or CN; wherein p is 0, 1 or 2; and A, B, C and D are carbon; its enantiomers, diastereomers, pharmaceutically acceptable salts and solvates thereof; with the provisos that: 1. R" may be hydrogen except when Z is SO, or when Z is O, NR 1 3 or S and the carbon to which it is attached is part of a double bond or when Y is SO2, CO 2

NR

1 8

SO

2 S(O)(NR23), or S(NR24)(NR 25 and 2. R 44 may be hydrogen except when U is SO, SO 2

NR

46

CO

2 or NR 49

SO

2 In another embodiment the compound has the following substituents: 1, m, r, s and t are 0 or 1; n is 1 or 2; Y is CHR' 2

SO

2 S03, C0 2

SO

2

NR'

4

CONR'

5 or without Y; is SO 2

SO

3 CO, C0 2 NR 1 3 S02 NR 1 4

CONR'

5 NR 3 1 SO 2 NR 31 NR 32 S02, NR 36

CO,

037 38 39 Co NR CONR or NR CO 2 00 In another ambodiment the compound has the following substituents: 1, r, s, and t is 0; Y is CHR' 2 So 2 So 2

NR'

4 or CONR' 5 or without Y; and Z is So 2 So 3 CO, CO 2

SO

2 NR CONR' 5

NR"

0 S02 NR NR 2 S02, NR 3 CO, NR" 7 or 3'i 39 IND CONR, NR CO 2 C) 10 In yet another embodiment the compound has the following substituents: R 7, R 8is halogen, nitro, cyano or U-R 4 wherein U is S, 0, NR 46

GO

2 NR 47 CONR 4 1, R 44 is hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, aralkyl, cycloalkyl, aryl, substituted aryl, heterocyclo or substituted heterocyclo, R 46 and R 47 is hydrogen, lower alkyl, aryl substituted alkyl or aryl.

In yet another embodiment the the salt is of an organic or inorganic acid.

In yet another embodiment the salt is of hydrogen chloride, hydrogen bromide, methanesulfonic acid, hydroxyethanesulfonic acid, sulfuric acid, acetic acid, trifluoroacetic acid, maleic acid, benzenesulfonic acid, toluenesulfonic acid, nitric acid, phosphoric acid, boric acid, tartaric acid, citric acid, succinic acid, benzoic acid, ascorbic acid or salicyclic acid.

In yet another embodiment the compound is: N-[6-bromo- 1,2,3,4-tetrahydro- 1 H-imidazol-4-ylmethyl)-3-quinolinyl]- Inaphthalenesulfonamide, dihydrochloride; N-[6-bromo- 1,2,3,4-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-3-quinolinyl]- 1naphthalenecarboxamide, d ihydrochloride; N-[6-bromo- 1,2,3 ,4-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-3-quinolinyl]-N- (phenylmethyl)methanesulfonamide, dihydrochloride; N-[6-bromo- 1,2,3 ,4-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-3-quinolinyl]benzenesulfonamide, dihydrochloride; N-[6-bromo- 1,2,3 ,4-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-3-quinolinyl]-N- (phenylmethyl)acetamide, dihydrochloride; N-[6-bromo- 1,2,3 ,4-tetrahydro- 1 H-imidazol-4-ylmethyl)-3-quinolinyl]-N-(4methoxyphenyl)methyl] methanesulfonamide, monohydrochioride; oN-[6-bromo-1I,2,3,4-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-3-quinolinyl]-N-[(4- 00 methylphenyl)methyl] methanesulfonamide monohydrochioride; N-[6-cyano- 1,2,3 ,4-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-3-quinolinyl]-N-[(3 methylphenyl)methyl]benzenesulfonamide monohydrochioride; N-[6-cyano- I ,2,3,4-tetrahydro- 1 H-imidazol-4-ylmethyl)-3-quinolinyl]-N-[(2methylphenyl)methyl]benzenesulfonamide monohydrochioride; IDN-[6-cyano- 1,2,3 ,4-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-3-quinolinyl]-N- C) 10 (phenylethyl)benzenesulfonamide monohydrochioride; N-[6-Cyano- 1,2,3 ,4-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-3-quinolinyl]-N-[(2ethoxyphenyl)methyl] benzenesulfonamide monohydrochioride; N-[6-Cyano- I ,2,3,4-tetrahydro- 1 H-imidazol-4-ylmethyl)-3-quinolinyl]-N- (phenylmethyl)benzenesulfonamide monohydrochioride; N-[6-Cyano- 1,2,3,4-tetrahydro- 1 H-imidazol-4-ylmethyl)-3-quinolinyl]-N-[(2,3dimethoxyphenyl)methyl] benzenesulfonamide monohydrochioride; N-[6-Cyano- 1,2,3 ,4-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-3-quinolinyl]-N-[(3 dimethylphenyl)methyl]benzenesulfonamide monohydrochioride; N- [6-Cyano- 1,2,3 ,4-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-3-quinolinyl]-N-[( 1naphthalenyl)methyl] benzenesulfonamide monohydrochioride; N-[6-Cyano- 1,2,3 ,4-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-3-quinolinyl]-N-[(2thiophene)methyl] benzenesulfonamide monohydrochioride; N-[6-Cyano- 1,2,3 ,4-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-3-quinolinyl]-N-[(2,5dimethylphenyl)methyljbenzenesulfonamide monohydrochioride; N-[6-Cyano- 1,2,3 ,4-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-3-quinolinyl]-N-[(3thiophene)methyl] benzenesulfonamide monohydrochioride; N-[6-Cyano- 1,2,3 ,4-tetrahydro- 1 H-imidazol-4-ylmethyl)-3-quinolinyl]-N-[(3chlorophenyl)methyl] benzenesulfonamide monohydrochioride; N-[6-Cyano- 1,2,3,4-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-3-quinolinyl]-N-[(2-.

fluorophenyl)methyl] benzenesulfonamide monohydrochioride; N-[6-Cyano- 1,2,3 ,4-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-3-quinolinyl]-N-[(3 pyridyl)methyl]benzenesulfonamide monohydrochioride; N-[6-Cyano- 1,2,3 ,4-tetrahydro- -(methyl)- 1H-imidazol-5-yl]methyl]-3-quinolinyl]-N- (phenylmethyl)benzenesul fonamide monohydrochioride; N-[6-Cyano- 1,2,3 ,4-tetrahydro- 1I-[[1I -(methyl)- I H-imidazol-5-yl]methyl]-3-quinolinyl]-N-[(3- __thiophenemethyl] benzenesul fonamide monohydrochioride; o N-[6-Cyano- 1,2,3 ,4-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-3-quinolinyl]-N- 00 (phenylmethyl)methanesulfonamide monohydrochioride; N-[6-Cyano- 1,2,3 ,4-tetrahydro-l1-[[1 -(methyl)- I H-imidazol-5-yl]methyl]-3-quinolinyl]-N- (phenylmethyl)methanesulfonamide monohydrochioride;- (R)-N-[6-Cyano- 1,2,3 ,4-tetrahydro- 1 -(methyl)- 1H-imidazol-5-yl]methyl]-3-quinolinyl]-N- (phenylmethyl)benzenesulfonamide monohydrochloride.

In yet another embodiment, the invention is a method of treating a synucleinopathic subject, the method comprising, administering to a synucleinopathic subject a farnesyl transferase inhibitor compound of the formula: R 8 7

,IR

11R 1 N-1 N Rr-SsTt-Y

R

1 R1, R 3

R

4 R1, R 6

N-T

R

9

R

10 or a stereoisomeric form, or a pharmaceutically acceptable acid or base addition salt form thereof, in a therapeutically effective amount, wherein Y is selected from the group consisting of CHR' 2

SO

2

SO

3 GO, Go 2 0, NR' 3

SO

2

NR"

4

CONR'

5

C(NCN),

C(NCN)NR'

6

NR'

7 CO, NR' 8 S02, CONR' 9

NR

20 S02 NR NR 22 S(0)(NR 2 3 and S(N 21)(R 2),or without Y; Z is selected from the group consisting of S, SO, SO 2

SO

3

GO,

GO

2 0, NR" 3

SO

2

NR"

4

CONR'

5 NR 26

NR

2 0NR 2 1, NR 29 0, NR" 0 S02 NR" 1 NR 1 2

SO

2 NR 3 1 C(NCN), NR 3 1 C(NCN)NR 35

NR

36 CO, NR 3 1 CONR 3 1, NR 3 9 C02, OCONR 4 1,

S(O)(NR

4 1 and S(NR 42 )(NR 43 R 7 and R 8 are selected from the group consisting of hydrogen, halo, nitro, cyano and U--R 44 U is selected from the group consisting of S, 0, NR 4 1, GO, So,

SO

2

GO

2 NR 46

GO

2 NR 47 GONR 48 NR 49

SO

2

NR"

0

SO

2

NR"

1 So 2 NR1 2

NR"

3

GO,

GONR

54 P0 2

R"

5 and P0 3

R

5 or without U; R 9 R1 0

R'

2

R'

3

R

4

R

5

R

6

R

7

R

8

R

9

R

ID

0 R21, R22 R23 R24, R25 R26 R27 R28, R29 R30, R31, R32 R33 R34 R35 R36 R37, R38, R39 R40 R41 C] R 42

R

43

R

44

R

4 5

R

46

R

47

R

48

R

49

R

5 ,R R 5

R

52

R

53

R

54

R

55

R

56

R

57

R

58 and R 59 are O selected from the group consisting of hydrogen, lower alkyl, aryl, heterocyclo, substituted alkyl OO and aryl; R" and R 44 are selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, aralkyl, cycloalkyl, aryl, substituted aryl, heterocyclo, and substituted heterocyclo; R 2

R

3

R

4

R

5 and R 6 are selected Sfrom the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, c alkynyl, substituted alkynyl, aralkyl, cycloalkyl, aryl, substituted aryl, heterocyclo, substituted I\O heterocyclo, cyano, alkoxycarbonyl, carboxy, carbamyl, and substituted carbamyl wherein 0 0 10 substituents on the nitrogen of the substituted carbamyl are selected from the group consisting of hydrogen, alkyl, substituted alkyl, aryl, aralkyl, substituted aryl, heterocyclo, and substituted heterocyclo; any two of R 2

R

3

R

4

R

5 and R 6 can join to form a cycloalkyl group; any two of R 2

R

3

R

4

R

5 and R 6 together can be oxo, except when the carbon atom bearing the substituent is part of a double bond; R, S and T are selected from the group consisting of CH 2 and CH(CH 2 )p Q wherein Q is NR 5 7

R

5 8

OR

59 or CN; p is 0, 1 or 2; and A, B, C and D are carbon; its enantiomer, diastereomer, pharmaceutically acceptable salt or solvate thereof; with the provisos that: 1. R" may be hydrogen except when Z is SO, or when Z is O, NR 1 3 or S and the carbon to which it is attached is part of a double bond or when Y is S0 2 C0 2

NR'

8 SO2,

S(O)(NR

23 or S(NR 24 )(NR25); and 2. R 44 may be hydrogen except when U is SO, SO 2

NR

46

CO

2 or NR 49

SO

2 In one embodiment of this aspect of the invention r, s and t are 0 or 1; Y is CHR 12

SO

2

SO

3 CO, CO 2

SO

2

NR

1 4

CONR

15 or without Y; Z is CR 1 2

SO

2

SO

3 CO, C0 2

NR

1 3

SO

2

NR

1 4

CONR'

5

NR

3 0

SO

2

NR

31

NR

32

SO

2

NR

36 CO, NR 37

CONR

3 8

NR

39

CO

2 or without Z.

In yet another embodiment r, s, and t is 0; Y is CHR 1 2 SO2, CO, SO 2

NR

1 4 or CONR 1 or without Y; and Z is CR' 2

SO

2

SO

3 CO, C0 2

SO

2

NR

1 4

CONR'

1

NR

30

SO

2

NR

3

NR

32

SO

2

NR

36 CO, NR 37

CONR

3 8

NR

39

CO

2 or without Z.

In yet another embodiments R 7

R

8 is halogen, nitro, cyano or U--R 44 wherein U is S, O,

NR

46 C0 2

NR

47

CONR

48

R

44 is hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, aralkyl, cycloalkyl, aryl, substituted aryl, heterocyclo or substituted heterocyclo, R 46 and R 47 is hydrogen, lower alkyl, aryl substituted alkyl or aryl.

In one embodiment the compound of the invention is selected from the group consisting 107 N-[6-bromo- 1,2,3 ,4-tetrahydro- 1 H-imidazol-4-ylmethyl)-3-quinolinyl]- 1 naphthalenesulfonamide, dihydrochioride; o N-[6-bromo- 1,2,3 ,4-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-3-quinolinyl]- 1- 00 ~naphthalenecarboxamide, d ihydrochloride; N-[6-bromo- 1,2,3 ,4-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-3-quinolinyl]-N- (phenylmethyl)methanesulfonamide, dihydrochioride; N-[6-bromo- 1,2,3 ,4-tetrahydro- I H-imidazol-4-ylmethyl)-3-quinolinyl]benzenesulfonamide, dihydrochioride; IND N-[6-bromo- 1,2,3 ,4-tetrahydro- 1 H-imidazol-4-ylmethyl)-3-quinolinyl]-N- C) 10 (phenylmethyl)acetamide, d ihydrochloride; N-[6-bromo- 1,2,3 ,4-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-3-quinolinyl]-N-(4methoxyphenyl)methyl] methanesulfonamide, monohydrochioride; N-[6-bromo-1I,2,3,4-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-3-quinolinyl]-N-[(4methylphenyl)methyll methanesulfonamide monohydrochioride; N-[6-cyano- 1,2,3 ,4-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-3-quinolinyl]-N-[(3methylphenyl)methyl] benzenesulfonamide monohydrochioride; N-[6-cyano- 1,2,3 ,4-tetrahydro- 1 H-imidazol-4-ylmethyl)-3-quinolinyl]-N-[(2methylphenyl)methyl] benzenesulfonamide monohydrochioride; N-[6-cyano- 1,2,3 ,4-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-3-quinolinyl]-N- (phenylethyl)benzenesulfonamide monohydrochioride; N-[6-Cyano- 1,2,3 ,4-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-3-quinolinyl]-N-[(2ethoxyphenyl)methyl] benzenesulfonamide monohydrochioride; N-[6-Cyano- 1,2,3 ,4-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-3-quinolinyl]-N- (phenylmethyl)benzenesulfonamide monohydrochioride; N-[6-Cyano- 1,2,3 ,4-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-3-quinolinyl]-N-[(2,3dimethoxyphenyl)methyl]benzenesulfonamide monohydrochioride; N-[6-Cyano-1I,2,3,4-tetrahydro- 1 H-imidazol-4-ylmethyl)-3-quinolinyl]-N-[(3 dimethylphenyl)methyl] benzenesulfonamide monohydrochioride; N-[6-Cyano- 1,2,3 ,4-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-3-quinolinyl]-N-[( 1naphthalenyl)methyl] benzenesulfonamide monohydrochioride; N-[6-Cyano- 1,2,3 ,4-tetrahydro- 1 H-imidazol-4-ylmethyl)-3-quinolinyl]-N-[(2thiophene)methyl]benzenesulfonamide monohydrochioride; N-[6-Cyano- 1,2,3 ,4-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-3-quinolinyl]-N-[(2,5dimethylphenyl)methyl] benzenesulfonamide monohydrochioride; N-[6-Cyano- 1,2,3 ,4-tetrahydro- 1 H-imidazol-4-ylmethyl)-3-quinolinyl]-N-[(3- __thiophene)methyl] benzenesul fonamide monohydrochioride; o N-[6-Cyano- 1,2,3 ,4-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-3-quinolinyl]-N-[(3- 00 chlorophenyl)methyl] benzenesulfonaniide monohydrochioride;, N-[6-Cyano- 1,2,3 ,4-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-3-quinolinyl]-N-[(2fluorophenyl)methyl] benzenesulfonamide monohydrochioride; N-[6-Cyano- 1,2,3 ,4-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-3-quinolinyl]-N-[(3pyridyl)methyl]benzenesulfonamide monohydrochioride; N-[6-Cyano- 1,2,3 ,4-tetrahydro-l1-[[1 -(methyl)- I H-imidazol-5-yl]methyl]-3-quinolinyl]-N- (phenylmethyl)benzenesul fonamide monohydrochioride; N-[6-Cyano- 1,2,3 ,4-tetrahydro-l1-[[1 -(methyl)- IH-imidazol-5-yl]methyl]-3-quinolinyl]-N-[(3thiophenemethyl] benzenesulfonamide monohydrochioride; N-[6-Cyano- 1,2,3 ,4-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-3-quinolinyl]-N- (phenylmethyl)methanesulfonamide monohydrochioride; N-[6-Cyano- 1,2,3 ,4-tetrahydro- 1 -(methyl)- 1 H-imidazol-5-yI]methyl]-3-quinolinyl]-N- (phenylmethyl)methanesulfonamide monohydrochioride; (R)-N-[6-Cyano- 1,2,3,4-tetrahydro- 1 -(methyl)- 1H-imidazol-5-yI]methyl]-3-quinolinyl]-N- (phenylmethyl)benzenesulfonamide monohydrochioride.

In another embodiment, the invention is a method of treating a synucleinopathic subject, the method comprising, administering to a synucleinopathic subject a farnesyl transferase inhibitor compound of the formula: 0 or a stereoisomeric form, or a pharmaceutically acceptable acid or base addition salt

C

form thereof, in a therapeutically effective amount.

C,)

0 00 In another aspect, the invention provides a method of treating a synucleinopathic subject by administering a famesyl transferase inhibitor compound of the formula: 6 R3 I I I b R7

R

6 V R7a

N

v R8 or a stereoisomeric form, or a pharmaceutically acceptable acid or base addition salt form thereof, in a therapeutically effective amount, wherein: one of a, b, c and d represents N or N+O and the remaining a, b, c, and d groups represent carbon, wherein each carbon has an R' or R 2 group bound to said carbon; or each of a, b, c, and d is carbon, wherein each carbon has an R' or R 2 group bound to said carbon; the dotted line represents optional bonds; X represents N or CH when the optional bond to C 1 is absent, and represents C when the optional bond to C11 is present; when the optional bond is present between carbon atom 5 and carbon atom 6 then there is only one A substituent bound to C-5 and there is only one B substituent bound to C-6 and A or B is other than H; when the optional bond is not present between carbon atom 5 and carbon atom 6 then there are two A substituents bound to C-5, wherein each A substituent is independently selected, and two B substituents bound to C-6, wherein each B substituent is independently selected, and wherein at least one of the two A substituents or one of the two B substituents are H, and wherein at least one of the two A substituents or one of the two B substituents is other than H; oA and B are independently selected from the group consisting of: H; -R 9; 00 R 9

-C(O)-R

9

-R?--CO

2

-R

9 a; -CH 2 2 1; -C(O)N(R 9 2 wherein each R 9 is the same or different; -C(O)NHR 9

C(O)NH-CH

2

-C(O)-NH

2 C(O)NHR 2; (10) CH 2 )pC(R 9

_OR

9 a; (11) (CH 2

)(R

9 2 wherein each R 9 is the same or different; (12) -(CH 2 )pC(O)R 9 (13) (CH 2 )pC(O)R 2 7 (14) (CH 2 )pC(O)N(R 9 2 wherein each R 9 is the same or different; (15) -C- 2 )pC(O)NH(R 9 (16) (CH 2 )pC(O)N(R 2 6 2 ID wherein each R 2 i the same or different; (17) -(F2p( 9a; (18) C 2 )pN(R 6 2 wherein R 26 i the same or different; (19) (CH 2 )pNHC(O)R 5 (20) -(CH 2 )pNHC(O) 2 (21)

(CH

2 )pN(C(O)R 2 7 wherein each R 27 a is the same or different; (22) -(CH 2 )pNR 1 C(O)R 2 1; (23) (CH 2 )pNR 1 C(O)R 2 7 wherein R 5 1 is not H, and R 5 1 and R 27 taken together with the atoms to which they are bound form a 5 or 6 membered heterocycloalkyl ring consisting; (24)

(CH

2 )pNR 5 C(O)NR 27 (25) -(CH 2 )pNR 5 C(O)NR 27 wherein R 5 1 is not H, and and R 27 taken together with the atoms to which they are bound form a 5 or 6 membered heterocycloalkyl ring; (26) -(CH 2 )pNR"C(O)N(R 2 'a) 2 wherein each R 27 a is the same or different; (27) (CH 2 )pNHSO 2

N(R

51 2 wherein each R 5 1 is the same or different; (28)-

(CH

2 )pNHCO 2 R 50 (29) (CH 2 )pNC(O)NHR 51 (30) -(CH 2 )pCO 2 R 5 1 (3 1) -NHR 9

R

30

-(CH

2 )p C R 9 1R 3 1 P (32) wherein R 30and R 3 1 are the same or different, and each p is independently selected;

R

30

R

32

-(CH

2 R 9

R

3

R

3 (33) wherein R 30 R 31 R 32 and R 33 are the same or different; (34)-alkeny-CO 2 R9a; alkenyl..C(O)R 9 a; (36)..alkenyl.C0 2 R 51 alkenyl..C(O)-R 27 a; (38) (CH 2 )p-alkenyl-CO 2 R 51 (37) -(CH 2 )pC=NOR 51 and (39) -(CH 2 )p-phthalimid; p is0, 1,2, 3or 4;

ID

Seach R' and R 2 is independently selected from the group consisting of: H; Halo; C, -CF 3

-OR

0 -CORi 0 -SR10; -S(O)tR' 5 wherein t is 0, 1 or 2; S N(Rl')2; -NO 2 (10) -OC(O)RO; (11) -CO 2

R'

1 (12) -OCO 2

R'

5 (13) -CN; (14) 00 NRi 0 COORi'; (15) -SR 5 C(O)ORi 5 (16) -SRi'N(R' 3 2 provided that R 1 5 in -SR'"N(R 3 2 is not -CH 2 and wherein each R is independently selected from the group consisting of: H and

C(O)OR'

5 (17) benzotriazol-1-yloxy; (18) tetrazol-5-ylthio; (19) substituted alkynyl; (21) alkenyl; and (22) alkyl, said alkyl or alkenyl group optionally being Cc substituted with halogen, -ORo 0 or -CO2R'; s R 3 and R 4 are the same or different and each independently represent H, and any of the 0 10 substituents of R' and R 2

R

5 R R 7 and R 7 a each independently represent: H, -CF 3

-COR

1 0 alkyl or aryl, said alkyl or aryl optionally being substituted with -S(O),R 1 5

-NROCOOR

5 -C(O)Ri or

CO

2

R'

1 or R 5 is combined with R6 to represent =0 or =S;

R

8 is selected from the group consisting of: O S O

R

11

I

O

R

11 R21 C R 11a R22 O N O C

R

1 2

R

46

R

9 is selected from the group consisting of: unsubstituted heteroaryl; substituted heteroaryl; arylalkoxy; substituted arylalkoxy; heterocycloalkyl; substituted heterocycloalkyl; heterocycloalkylalkyl; substituted heterocycloalkylalkyl; (9) unsubstituted heteroarylalkyl; (10) substituted heteroarylalkyl; (11) unsubstituted heteroarylalkenyl; (12) substituted heteroarylalkenyl; (13) unsubstituted heteroarylalkynyl and (14) substituted heteroarylalkynyl; wherein said substituted R 9 groups are substituted with one or more substituents selected from the group consisting of: -OH; -CO 2

R

1 4

-CH

2

OR

1 4 halogen; alkyl; amino; trityl; heterocycloalkyl; cycloalkyl; (10) arylalkyl; (11) heteroaryl; (12) heteroarylalkyl and

D.)

0 wherein R 14 is independently selected from the group consisting of: H; alkyl; aryl, arylalkyl, heteroaryl and heteroarylalkyl;

SR

9 a is selected from the group consisting of: alky and arylalkyl; R10 is selected from the group consisting of: H; alkyl; aryl and arylalkyl; \S R" is selected from the group consisting of: alkyl; substituted alkyl; (3) Sunsubstituted aryl; substituted aryl; unsubstituted cycloalkyl; substituted cycloalkyl; unsubstituted heteroaryl; substituted heteroaryl; heterocycloalkyl; and substituted heterocycloalkyl; wherein said substituted alkyl, substituted cycloalkyl, and substituted heterocycloalkyl R" groups are substituted with one or more substituents selected from the group consisting of: -OH; fluoro; and alkyl; and wherein said substituted aryl and substituted heteroaryl R" groups are substituted with one or more substituents independently selected from the group consisting of: -OH; halogen; and alkyl;

R'

la is selected from the group consisting of: H; OH; alkyl; substituted alkyl; unsubstituted aryl; substituted aryl; unsubstituted cycloalkyl; substituted cycloalkyl; unsubstituted heteroaryl; (10) substituted heteroaryl; (11) heterocycloalkyl; and (12) substituted heterocycloalkyl; wherein said substituted alkyl, substituted cycloalkyl, and substituted heterocycloalkyl R' groups are substituted with one or more substituents independently selected from the group consisting of: -OH; -CN; -CF 3 (4) fluoro; alkyl; cycloalkyl; heterocycloalkyl; arylalkyl; heteroarylalkyl; alkenyl and (11) heteroalkenyl; and wherein said substituted aryl and substituted heteroaryl R" a groups have one or more substituents independently selected from the group consisting of: (1) -OH; -CN; -CF 3 halogen; alkyl; cycloalkyl; heterocycloalkyl; (8) arylalkyl; heteroarylalkyl; (10) alkenyl; and (11) heteroalkenyl;

R

1 2 is selected from the group consisting of: H, alkyl, piperidine Ring V, cycloalkyl, and -alkyl-(piperidine Ring V);

R

1 5 is selected from the group consisting of: alkyl and aryl;

R

21

R

22 and R 46 are independently selected from the group consisting of: (2) alkyl; unsubstituted aryl; substituted aryl substituted with one or more substituents independently selected from the group consisting of: alkyl, halogen, CF 3 and OH; unsubstituted cycloalkyl; substituted cycloalkyl substituted with one or more substituents

ID

independently selected from the group consisting of: alkyl, halogen, CF 3 and OH; heteroaryl of the formula, c- V 00

N

r' and O and heterocycloalkyl of the formula:

I

c N 44 wherein R 44 is selected from the group consisting of: alkyl; alkylcarbonyl; (d) alkyloxy carbonyl; haloalkyl; and -C(O)NH(R 51

R

26 is selected from the group consisting of: H; alkyl; alkoxyl; -CH 2 CN; R 9

-CH

2

CO

2 H; -C(O)alkyl; and CH 2

CO

2 alkyl;

R

27 is selected from the group consisting of: -OH; alkyl; and (4) alkoxy;

R

2 7a is selected from the group consisting of: alkyl; and alkoxy;

R

30

R

3 1

R

32 and R 33 are independently selected from the group consisting of: -H; -OH; alkyl; aryl phenyl); arylalkyl benzyl); -OR 9 a; (8)

-NH

2

-NHR

9 a; and (10)--N(R 9 a) 2 wherein each R 9 a is independently selected;

R

50 is selected from the group consisting of: alkyl; unsubstituted heteroaryl; (3) substituted heteroary; and amino; wherein said substituents on said substituted R 5 0 groups are independently selected from the group consisting of: alkyl, halogen, and -OH;

R

51 is selected from the group consisting of: H, and alkyl; provided that a ring carbon atom adjacent to a ring heteroatom in a substituted heterocycloalkyl moiety is not substituted with a heteroatom or a halo atom; and provided that a ring carbon atom, that is not adjacent to a ring heteroatom, in a substituted heterocycloalkyl moiety, is not substituted with more than one heteroatom; and provided that a ring carbon atom, that is not adjacent to a ring heteroatom, in a substituted heterocycloalkyl moiety, is not substituted with a heteroatom and a halo atom; and provided that a ring carbon in a substituted

I

cycloalkyl moiety is not substituted with more than one heteroatom; and provided that a carbon atom in a substituted alkyl moiety is not substituted with more than one heteroatom; and provided that the same carbon atom in a substituted alkyl moiety is not substituted with both heteroatoms and halo atoms.

In one embodiment, the compound has the formula: X=CH or N; B is H when the optional bond is present between C-5 and C-6, and when the optional bond between C-5 and C-6 is absent then each B is H.

In another embodiment, the compound has the formula: X=CH or N; A is H when the optional bond is present between C-5 and C-6, and when the optional bond between C-5 and C-6 is absent then each A is H.

ID

In any embodiment of this aspect of the invention, R' to R 4 each may be independently S selected from H or halo. R 5 to R 7 may be H. In one embodiment, a may be N and the O remaining b, c and d substituents may be carbon. In another embodiment, a, b, c, and d may be OO carbon. The optional bond between C-5 and C-6 may be present. Alternatively, the optional bond between C-5 and C-6 may be absent. R 8 may be group 2.0, or 4.0. One of A and B may be H and the other may be R 9

R

9 may be selected from the group consisting of: (1) Sheterocycloalkylalkyl of the formula -(CH 2 )n-heterocycloalkyl; substituted Cc heterocycloalkylalkyl of the formula -(CH 2 )n-substituted heterocycloalkyl; unsubstituted IN heteroarylalkyl of the formula -(CH 2 )n-heteroaryl; and substituted heteroarylalkyl of the 0 10 formula -(CH 2 )n-substituted heteroaryl; wherein n is 1, 2, or 3 and the substituents for said substituted R 9 groups are each independently selected from the group consisting of: -OH;

-CO

2

R'

4

-CH

2

OR

1 4 halo, alkyl; amino; trityl; heterocycloalkyl; (8) arylalkyl; heteroaryl and (10) heteroarylalkyl. wherein R 14 is independently selected from the group consisting of: H and alkyl. In another embodiment, R 9 may be selected from the group consisting of: -(CH 2 )n-imidazolyl; -(CH 2 )n-substituted imidazolyl;

(CH

2 )n-morpholinyl; -(CH 2 ),-substituted morpholinyl, -(CH 2 )n-piperazinyl, and (6)

-(CH

2 ),-substituted piperazinyl, wherein n is 1, 2, or 3. R" may be selected from the group consisting of: alkyl, cycloalkyl and substituted cycloalkyl wherein the substituents are selected from the group consisting of: halo, alkyl and amino; and R' a may be selected from: alkyl, unsubstituted aryl,

V

N+

R44 and substituted aryl, cycloalkyl or substituted cycloalkyl, wherein the substituents on said substituted groups are selected from the group consisting of: halo, -CN or CF 3

R

2

R

2 and

R

22 are H; and R 4 6 is selected from the group consisting of: unsubstituted aryl, 2247 substituted aryl wherein the substituents are selected from the group consisting of: alkyl, alkylcarbonyl and haloalkyl, and wherein R 44 is selected from the group consisting of: H or

C(O)NH

2 In another embodiment, R 8 may be selected from the group consisting of: group wherein R" is selected from the group consisting of: t-butyl and cyclohexyl; group wherein is selected from the group consisting of: methyl and t-butyl; group 4.0 wherein,

ID

O RI 2 is H, and R la is selected from the group consisting of: t-butyl, cyanophenyl, chlorophenyl, S fluorophenyl and cyclohexyl; group 5.0 wherein R 21 and R 22 are H, and R 46 is selected from 2O the group consisting of: 00 N N+ N O, R44 0 5 wherein R 44 is -C(O)NH 2

R

8 may be group Ci In one embodiment, the optional bond between C5 and C6 may be present and A is H and B is R 9 In one embodiment, R' to R 4 each may be independently selected from the group consisting of: H and halo; R 5

R

6

R

7 and R 7 a are H; a is N and the remaining b, c and d substituents are carbon; the optional bond between C5 and C6 is present; A is H; B is R9; R 8 is group 2.0 or 4.0; R" is selected from the group consisting of: alkyl, cycloalkyl and substituted cycloalkyl wherein the substituents are selected from the group consisting of: halo, alkyl and amino; RI ais selected from the group consisting of: alkyl, unsubstituted aryl, substituted aryl, cycloalkyl or substituted cycloalkyl, wherein the substituents on said substituted groups are are selected from the group consisting of: halo, -CN and CF 3 (10) R12 is H; (11) R 9 is selected from the group consisting of: -(CH 2 )n-heterocycloalkyl;

(CH

2 ),-substituted heterocycloalkyl; -(CH 2 ),-heteroaryl, and -(CH 2 )n-substituted heteroaryl; wherein n is 1, 2, or 3 and the substituents for said substituted R 9 groups are each independently selected from the group consisting of: -OH; -CO 2

R

4

-CH

2 0R' 4 halo, alkyl; amino; trityl; heterocycloalkyl; arylalkyl; (10) heteroaryl and (11) heteroarylalkyl; wherein R 14 is independently selected from the group consisting of: H and alkyl; and (12) X is N or CH.

In another embodiment, R' to R 4 each may be independently selected from H, Br or Cl; R 9 is selected from the group consisting of: -(CH 2 )n-imidazolyl; -(CH 2 )nsubstituted imidazolyl; -(CH 2 )n-morpholinyl; (CH 2 )n-substituted morpholinyl,

(CH

2 )n-piperazinyl, or -(CH 2 )n-substituted piperazinyl, wherein n is 1, 2, or 3; R" is selected from the group consisting of: t-butyl and cyclohexyl; R 1 2 is H; and R' a is selected from the group consisting of: t-butyl, cyanophenyl, chlorophenyl, fluorophenyl and cyclohexy.

In yet another embodiment, R' and R 2 are H; R 3 is H; R 4 is Cl; R 8 is wherein R'la is cyanophenyl; and R 1 2 is H; and R 9 is selected from the group consisting of:

-CH

2 -imidazolyl, and -CH 2 -imidazolyl wherein said imidazolyl moiety is substituted with a methyl group.

In one embodiment, the famesyl transferase inhibitor compound may have the formula: X may be N.

In one embodiment, the famesyl transferase inhibitor compound may have the formula:

(R

3 A)m wherein:

OD

one of a, b, c and d represents N or N O and the remaining a, b, c, and d groups S represent CR' wherein each R' group on each carbon is the same or different; or O each a, b, c, and d group represents CR' wherein each R' group on each carbon is the 00 same or different; the dotted lines represent optional bonds; X represents N or CH when the optional bond to C11 is absent, and represents C \when the optional bond to Cl is present; R' is selected from the group consisting of: H; halo; -CF 3

-OR

1 0 \o COR'O; -SR"o; -S(O)tRI5; -NO 2 (10) -OC(O)RI°; (11) 0 10 CO 2 R; (12) -OCO 2

RI

0 (13) -CN; (14) -NRoCOOR"S; (15) -SRsC(O)OR 15 (16)

SR'

5

N(R

3 2 wherein each R' 3 is independently selected from the group consisting of: H and

C(O)OR'

5 and provided that R' 5 in -SR i

'N(R'

3 2 is not -CH 2 (17) benzotriazol-1-yloxy; (18) tetrazol-5-ylthio; (19) substituted tetrazol-5-ylthio; (20) alkynyl; (21) alkenyl; (22) alkyl; (23) alkyl substituted with one or more substitutents independently selected from the group consisting of: halogen, -OR 1 0 and -CO 2

R'

1 (24) alkenyl substituted with one or more substitutents independently selected from the group consisting of: halogen, -OR i0 and

CO

2 Each R is independently selected from the group consisting of: halo; -CF 3

-OR

0

COR

1 0 -SR1; -S(O)tR' 5

-N(R

0 2

-NO

2

-OC(O)R

0 (10) CO 2 R'O; (11)-OCO 2

RI

0 (12) -CN; (13) -NRICOORIS; (14) -SRIsC(O)ORi'; -SR'SN(R 3 2 wherein each R 1 3 is independently selected from the group consisting of: H and

-C(O)OR'

5 and provided that R 1 5 in -SR 15

N(R'

3 2 is not -CH 2 (16) benzotriazol-1-yloxy; (17) tetrazol-5-ylthio; (18) substituted tetrazol-5-ylthio; (19) alkynyl; (20) alkenyl; (21) alkyl; (22) alkyl substituted with one or more substitutents independently selected from the group consisting of: halogen, -OR 1 0 and -CO 2

R

1 and (23) alkenyl substituted with one or more substitutents independently selected from the group consisting of: halogen, -OR' 0 and

CO

2

R°;

m is 0, 1 or 2; t is 0, 1 or 2 R, R, R 7 and R 7 are each independently selected from the group consisting of: (1) H; -CF 3

-COR

1 0 alkyl; unsubstituted aryl; alkyl substituted with one or more groups selected from the group consisting of: -OR 1 0 -SRO, -S(O),R 1 5 NRioCOOR" 1

-N(R

0 2

-NO

2

-C(O)R

0 -OCORO, -OCO 2

R

1 5

CO

2

R'

0 and OPO 3

R

0 and aryl substituted with one or more groups selected from the group consisting of: -OR i0 0 -S(0)tR 1 5

-NR

1 oCOOR 5

-N(R'

0 )2'-N0 2

-OCOR

0

-OCO

2

R

5

-CO

2

R

1 0 and OPO 3 Ri 0 or o R 5 together with R 6 represents =0 or =S; 00 R 8 is selected from the group consisting R11 ri of: 0 R 11 8 R 2 1 1 R 11 R22 O N O C

R

12

R

46

R'

1 is selected from the group consisting of: H; alkyl; aryl and arylalkyl; R" is selected from: alkyl; substituted alkyl; unsubstituted aryl; substituted aryl; unsubstituted cycloalkyl; substituted cycloalkyl; unsubstituted heteroaryl; substituted heteroaryl; heterocycloalkyl; and (10) substituted heterocycloalkyl; wherein said substituted alkyl, substituted cycloalkyl, and substituted heterocycloalkyl groups are substituted with one or more substituents selected from the group consisting of: -OH; fluoro; and alkyl; and wherein said substituted aryl and substituted heteroaryl groups are substituted with one or more substituents selected from the group consisting of: -OH; halogen; and alkyl; R is selected from the group consisting of: H; OH; alkyl; substituted alkyl; unsubstituted aryl; substituted aryl; unsubstituted cycloalkyl; substituted cycloalkyl; unsubstituted heteroaryl; (10) substituted heteroaryl; (11) heterocycloalkyl; and (12) substituted heterocycloalkyl; wherein said substituted alkyl, substituted cycloalkyl, and substituted heterocycloalkyl R' a groups are substituted with one or more substituents selected from the group consisting of: -OH; -CN; -CF 3 fluoro; alkyl; (6) cycloalkyl; heterocycloalkyl; arylalkyl; heteroarylalkyl; (10) alkenyl and (11) heteroalkenyl; and wherein said substituted aryl and substituted heteroaryl R' 1 a groups are substituted with one or more substituents selected from the group consisting of: -OH; (2) -CN; -CF 3 halogen; alkyl; cycloalkyl; heterocycloalkyl; arylalkyl; (9) heteroarylalkyl; (10) alkenyl and (11) heteroalkenyl; R' 2 is selected from the group consisting of: H, alkyl, piperidine Ring V, cycloalkyl, and -alkyl-(piperidine Ring V);

OD

S(P) R' 5 is selected from the group consisting of: alkyl and aryl;

C

R

2 1

R

22 and R 46 are independently selected from the group consisting of: H; (2) O alkyl; unsubstituted aryl; substituted aryl substituted with one or more substituents oO selected from the group consisting of: alkyl, halogen, CF 3 or OH; unsubstituted cycloalkyl; substituted cycloalkyl substituted with one or more substituents selected from the group consisting of: alkyl, halogen, CF 3 or OH; heteroaryl of the formula, ¢0, piperidine Ring V: h

V

N

R44 wherein R 44 is selected from the group consisting of: H, alkyl; alkylcarbonyl; (d) alkyloxy carbonyl; haloalkyl and -C(O)NH(R 51

R

51 is selected from the group consisting of: -H and alkyl methyl, ethyl, propyl, butyl and t-butyl); B is the group:

R

30

(CH

2 C R 9 p in said B group: p of the -(CH 2 moiety is 0; p of the

R

3 0

R

9

C,\

IO

moiety is 1 to 3; when p is one for the moiety

O

C R 9

R

31

P

IN then R 30 is selected from the group consisting of: -OH and -NH 2 and R 31 is alkyl; when S3 p is 2 or 3 for the moiety

SO

R

30

R

R

p then: for one -CR 30

R

31 moiety, R 30 is selected from the group consisting of: -OH and

-NH

2 and R 3 is alkyl; and for the remaining -CR 30

R

3 1- moieties R 30 and R 31 are hydrogen; and R 9 is unsubstituted heteroaryl or substituted heteroaryl, provided that when said heteroaryl group contains nitrogen in the ring, then said heteroaryl group is not bound by a ring nitrogen to the adjacent -CR 3 0

R

31 moiety when R 30 is -OH or -NH 2 In one embodiment, a is N; b, c and d are CR' groups wherein all of said R' substituents are H, or one R' substituent is halo and the remaining two R' substituents are hydrogen; m is 1, and R 3 A is halo, or m is 2 and each R 3 A is the same or different halo Br or Cl); and R 5

R

6

R

7 and R 7 a are H.

In one embodiment, the farnesyl transferase inhibitor compound may have the formula: r

,(R

3 Am wherein: B is the group:

(CH

2 C R 9

P

in said B group: p of the -(CH 2 moiety is 0; p of the moiety is I to 3; when p is one for the moiety

R

I

C

then R 30 is selected from the group consisting of: -OH and -NH 2 and R 31 is alkyl; when p is 2 or 3 for the moiety cD R 0 R 9 0 3 0 R 9 then: for one -CRR 31 moiety, R 30 is selected from the group consisting of: -OH and ID -NH 2 and R 31 is alkyl; and for the remaining -CR 30

R

31 moieties R 30 and R 3 1 are n hydrogen; and R 9 is unsubstituted heteroaryl or substituted heteroaryl, provided that when O 5 said heteroaryl group contains nitrogen in the ring, then said heteroaryl group is not bound by a ring nitrogen to the adjacent -CR3R 3 1 moiety when R 30 is -OH or -NH 2 a is N; b, c and d are CR' groups wherein all of said R' substituents are H, or one R' substituent is halo and the remaining two R' substituents are hydrogen; m is 1, and R 3 A is halo, or m is 2 and each R 3 A is the same or different halo; X is N or CH;

R

5

R

6

R

7 and R 7 a are H; R is selected from the group consisting of: O= S= O

I

0

R

1 R 2 1 R11a R22 O N O C

R

12

R

46 R" is selected from: alkyl; substituted alkyl; unsubstituted aryl; (4) substituted aryl; unsubstituted cycloalkyl; substituted cycloalkyl; unsubstituted heteroaryl; substituted heteroaryl; heterocycloalkyl; and (10) substituted heterocycloalkyl; wherein said substituted alkyl, substituted cycloalkyl, and substituted heterocycloalkyl R" groups are substituted with one or more substituents selected from the group consisting of: -OH; fluoro; and alkyl; and wherein said substituted aryl and substituted heteroaryl R" groups are substituted with one or more substituents selected from the group consisting of: -OH; halogen; and alkyl;

ID

R a is selected from the group consisting of: H; OH; alkyl; substituted alkyl; unsubstituted aryl; substituted aryl; unsubstituted cycloalkyl; substituted O cycloalkyl; unsubstituted heteroaryl; (10) substituted heteroaryl; (11) heterocycloalkyl; and 00 (12) substituted heterocycloalkyl; wherein said substituted alkyl, substituted cycloalkyl, and substituted heterocycloalkyl R' a groups are substituted with one or more substituents selected from the group consisting of: -OH; -CN; -CF 3 fluoro; alkyl; (6) cycloalkyl; heterocycloalkyl; arylalkyl; heteroarylalkyl; (10) alkenyl and (11) heteroalkenyl; and wherein said substituted aryl and substituted heteroaryl R l la groups are IN substituted with one or more substituents selected from the group consisting of: -OH; (2) 0 10 -CN; -CF 3 halogen; alkyl; cycloalkyl; heterocycloalkyl; arylalkyl; (9) heteroarylalkyl; (10) alkenyl and (11) heteroalkenyl;

R

1 2 is selected from the group consisting of: H, alkyl, piperidine Ring V, cycloalkyl, and -alkyl-(piperidine Ring V);

R

21

R

2 2 and R 46 are independently selected from the group consisting of: H; (2) alkyl; unsubstituted aryl; substituted aryl substituted with one or more substituents selected from the group consisting of: alkyl, halogen, CF 3 or OH; unsubstituted cycloalkyl; substituted cycloalkyl substituted with one or more substituents selected from the group consisting of: alkyl, halogen, CF 3 or OH; heteroaryl of the formula,

O

piperidine Ring V:

V

N

R

44 wherein R 44 is selected from the group consisting of: H, alkyl; alkylcarbonyl; (d) alkyloxy carbonyl; haloalkyl and and

R

51 is selected from the group consisting of: H and alkyl methyl, ethyl, propyl, butyl and t-butyl).

In one embodiment, in the B group: p of the moiety is 0; p of the moiety is 1 to 2; when p is one for the moiety N 'p then R 30 is selected from the group consisting of: -OH and -NH 2 and R 31 is CI-C 2 alkyl; (4) when p is 2 or 3 for the moiety

R

30 C- R 9

R

31 then: for one -CR30R 3 moiety, R 30 is selected from the group consisting of: -OH and

-NH

2 and R 31 is Ci-C 2 alkyl; and for the remaining -CR 30

R

3 moieties R 30 and R 31 are hydrogen; and R 9 is imidazolyl or substituted imidazolyl, provided that said imidazolyl group is not bound by a ring nitrogen to the adjacent -CR 30

R

3 1_ moiety when R 30 is -OH or

-NH

2

OR

S(B) R 8 is R' is alkyl; S(D) XisN; 00 b, c and d are CR' groups wherein all of said R' substituents are H; m is 1, and R 3A is halo; and (G)X is N.

O

c In one embodiment, in the B group: p of the -(CH 2 moiety is 0; p of the

(N

R

3 0 C R 9 I R

R

31

P

moiety is 1; R 3 0 is selected from the group consisting of: -OH and -NH 2 and R 31 is C 1

C

2 alkyl; and R 9 is substituted imidazolyl wherein said the substituent is an alkyl group, provided that said imidazolyl group is not bound by a ring nitrogen to the adjacent

CR

30

R

31 moiety.

In another embodiment, in said B group: p of the -(CH 2 moiety is 0; p ofthe p

R

3 moiety is 1; R 30 is -OH, and R 3 is methyl; and R 9 is substituted imidazolyl wherein the substituent is a methyl group, provided that said imidazolyl group is not bound by a ring nitrogen to the adjacent -CR 30

R

31 moiety; and R 3 A is Cl; and R' 1 is alkyl.

R

9 may be

H

3

C

R" may be t-butyl.

In one embodiment, the farnesyl transferase inhibitor compound may have the formula: 6 (R 3 A)m Iv R6 R7a R

R

wherein all substituents may be as defined above.

In one embodiment, the farnesyl transferase inhibitor compound may have the formula: R3111,,. R9 6 R3A m d I b N IV

R

8 wherein all substituents may be as defined above.

In one embodiment, the farnesyl transferase inhibitor compound may have the formula: 0R3 00 5 6 (R3A)m /d c

R

7 wherein all substituents may be as defined above.

In one embodiment, in the B group: p of the -(CH 2 moiety is 0; p of the

RR

30

I-R

moiety is 1; R 3 0 is-OH, and R 3 is methyl; and R 9 is substituted imidazolyl wherein the substituent is a methyl group, provided that said imidazolyl group is not bound by a ring nitrogen to the adjacent -CR 3 0

R

31 moiety; and R 3 A is Cl; and R" is alkyl.

R

9 may be R ein all substituents may be t-butyl.

In one embodiment, in the B group: p of the (CH 2 moiety is 0; p of the 4 R 3 C R9 R a may be t-butyl.

In one embodiment, in the B group: p of the -(CH2)p- moiety is 0; p of the 129

O

C IR 30 SC R 9 00 I RI

P

moiety is 1; R 3 0 is -OH, and R 3 1 is methyl; and R 9 is substituted imidazolyl wherein ,O the substituent is a methyl group, provided that said imidazolyl group is not bound by a ring Cc, nitrogen to the adjacent -CR 3 0

R

31 moiety; and R 3 A is Cl; and R" is alkyl.

R

9 may be

H

3

C

N

N

R" may be t-butyl.

In another aspect, the invention provides a method of treating a synucleinopathic subject by administering a farnesyl transferase inhibitor compound of the formula: A ,B R1d R2 R4 R7 Iv

RR

or a stereoisomeric form, or a pharmaceutically acceptable acid or base addition salt form thereof, in a therapeutically effective amount, wherein:

IO

one of a, b, c and d represents N or NO and the remaining a, b, c, and d groups represent S carbon, wherein each carbon has an R' or R 2 group bound to said carbon; or O each of a, b, c, and d is carbon, wherein each carbon has an R' or R 2 group bound to said 00 carbon; the dotted lines represent optional bonds; X represents N or CH when the optional bond is absent, and represents C when the l optional bond is present; when the optional bond is present between carbon atom 5 and carbon atom 6 then there is only one A substituent bound to carbon atom 5 and there is only one B substituent 0 10 bound to carbon atom 6 and A or B is other than H; when the optional bond is not present between carbon atom 5 and carbon atom 6, then there are two A substituents bound to carbon atom 5 and two B substituents bound to carbon atom 6, wherein each A and B substituent is independently selected from the group consisting of:

-R

9

-R

9

-C(O)-R

9

-R

9

-CO

2

-R

9 a; -(CH 2 )pR 26

C(O)N(R

9 2 wherein each R 9 is the same or different; -C(O)NHR 9

-C(O)NH-

CH

2

-C(O)-NH

2 -C(O)NHR26; (10) -(CH 2 )pC(R 9 R9a; (11) -(CH 2 )p(R 9 2 wherein each R 9 is the same or different; (12) (CH 2 )pC(O)R 9 (13) -(CH 2 )pC(O)R 27 a (14) -(CH 2 )pC(O)N(R 9 2 wherein each R 9 is the same or different; (15)

(CH

2 )pC(O)NH(R 9 (16) (CH 2 )pC(O)N(R 26 2 wherein each R 26 is the same or different; (17) -(CH 2 )pN(R9)-R9a; (18) -(CH 2 )pN(R 26 2 wherein R 26 is the same or different; (19)

-(CH

2 )pNHC(O)Rs°; (20) -(CH 2 )pNHC(0) 2 R5; (21) (CH 2 )pN(C(O)R27a)2 wherein each

R

2 7a is the same or different; (22) (CH 2 )pNRsC(O)R27, or R 51 and R 27 taken together with the atoms to which they are bound form a heterocycloalkyl ring consisting of, 5 or 6 members, provided that when R 51 and R 27 form a ring, R 51 is not H; (23)

(CH

2 )pNR 5 1

C(O)NR

27 or R s 5 and R 27 taken together with the atoms to which they are bound form a heterocycloalkyl ring consisting or 5 or 6 members, provided that when R 51 and R 27 form a ring, R 51 is not H; (24) -(CH 2 )pNR 5 C(O)N(R27a)2, wherein each R 27a is the same or different; (25) -(CH 2 )pNHSO 2

N(R

5 1 2 wherein each R 5 is the same or different; (26)

(CH

2 )pNHCO 2

R

5 0 (27) -(CH 2 )pNC(O)NHR 1 (28) (CH 2 )pCO 2

R

5 (29) -NHR 9 c-I R 30 o (CH 2 )p C R

R

31 P wherein R 3and R 3 1 are the same or different; IND R 30

R

32 -(C2)P C- C R 9

R

31

R

33 (31) wherein R 30 R 3 1 R 32 and R 33 are the same or different; (32) -alkenyl-CO 2

R

9 (33) -alkenyl- C(O)R 9; (34) -alkenyl-C0 2 R 51 (35) -alkenyl-C(O)-R 21; (36) (CH 2 )p-alkenyl-C0 2 -R 51 (37)

-(CH

2 )pC=NOR 5 and (38) (CH 2 )P-Phthalimid; p isO0, 1, 2, 3or 4; each R1 and R 2 is independently selected from H, Halogen, -CF 3

-OR"

0

COR'

0

SR'

0 wherein t is 0, 1 or 2, -N(R' 0 2

-NO

2

-OC(O)R'

0

CO

2

R'

0

-OCO

2 R 1 5

-CN,

-NR' COOR", -SR 15C(O)OR 1 5

-SR

5 N(R1 3 2 provided that R" in -SR 15N(R 13)2 is not

CH

2 and wherein each R 1 3 is independently selected from H or -C(O)OR 5 benzotriazol- I yloxy, tetrazol-5-ylthio, or substituted tetrazol-5-ylthio, alkynyl, alkenyl or alkyl, said alkyl or alkenyl group optionally being substituted with halogen, -OR 10 or -0RO R 3 and R 4 are the same or different and each independently represent H, or any of the substituents of R 1 and R 2 R 5, R 6, R7 and R 7 a each independently represent H, CF 3 -COR 0, alkyl or aryl, said alkyl or aryl optionally being substituted with -OR 0 10R', -S(O)tR 5

-NR

0

COOR

5

N(R

1 0 2

-NO

2

-C(O)R'

0

-OCOR'

0

-OCO

2

R'

5

-CO

2

R'

0

OPO

3

R'

0 or R 5 is combined with R 6 to represent =0 or =S; R 8is selected from the group consisting of:.

N /R2 HO 0 N

ID

R

9 is selected from the group consisting of: heteroaryl; substituted heteroaryl; (3) S arylalkoxy; substituted arylalkoxy; heterocycloalkyl; substituted heterocycloalkyl; O heterocycloalkylalkyl; substituted heterocycloalkylalkyl; heteroarylalkyl; OO substituted heteroarylalkyl; (11) heteroarylalkenyl; (12) substituted heteroarylalkenyl; (13) heteroarylalkynyl; (14) substituted heteroarylalkynyl; (15) arylalkyl; (16) substituted arylalkyl; (17) alkenyl, and (18) substituted alkenyl; wherein said substituted R 9 groups are substituted with one or more substituents selected from the group consisting of: OH; -CO 2

R

14

-CH

2 0R 14 halogen; alkyl; amino; trityl; (8) ("1 IN heterocycloalkyl; cycloalkyl; (10) arylalkyl; (11) heteroaryl; (12) heteroarylalkyl and (13) wherein

R'

4 is independently selected from the group consisting of: H; alkyl; aryl, arylalkyl, heteroaryl and heteroarylalkyl;

R

9 a is selected from the group consisting of: alky and arylalkyl;

R'

1 is selected from the group consisting of: H; alkyl; aryl and arylalkyl; R" is selected from the group consisting of: alkyl; substituted alkyl; aryl; (4) substituted aryl; cycloalkyl; substituted cycloalkyl; heteroaryl; (8) substituted heteroaryl; heterocycloalkyl; and (10) substituted heterocycloalkyl; wherein said substituted R' 1 groups have 1, 2 or 3 substituents selected from the group consisting of: -OH; halogen and alkyl; R' a is selected from the group consisting of: H; OH; alkyl; substituted alkyl; aryl; substituted aryl; cycloalkyl; substituted cycloalkyl; heteroaryl; substituted heteroaryl; (11) heterocycloalkyl; and (12) substituted heterocycloalkyl; wherein said substituted R la groups have one or more substituents selected from the group consisting of: -OH; -CN; CF 3 halogen; alkyl; cycloalkyl; (7) heterocycloalkyl, arylalkyl; heteroarylalkyl; (10) alkenyl and (11) heteroalkenyl;

R

1 2 is selected from the group consisting of: H, and alkyl;

R

15 is selected from the group consisting of: alkyl and aryl; R 21

R

2 2 and R46 are independently selected from the group consisting of: alkyl; aryl; substituted aryl, optionally substituted with one or more substituents selected

ID

from the group consisting of: alkyl, halogen, CF 3 and OH; cycloalkyl; substituted S cycloalkyl; optionally substituted with one or more substituents selected from the group O consisting of: alkyl, halogen, CF 3 and OH; heteroaryl of the formula, 00 Sand 0; N 5 and heterocycloalkyl of the formula:

\O

V

N

R44 wherein R 44 is selected from the group consisting of: alkyl; alkylcarbonyl; (4) alkyloxy carbonyl; haloalkyl and -C(O)NH(R 5 when R 21

R

22 or R 46 is the heterocycloalkyl of the formula above, Ring V is selected from the group consisting of:

NN

10 R 4 4 4 4

R

4 4

NH

R

N.)

00 CO2C2H5, C(O)NH 2 and C CO2-t-BUTYL;

O

O R 26 is selected from the group consisting of: alkyl; alkoxyl; -CH2-CN; R9; -CH 2

CO

2 H; -C(O)alkyl and CH 2

CO

2 alkyl;

R

27 is selected from the group consisting of: -OH; alkyl and alkoxy;

R

27a is selected from the group consisting of: alkyl and alkoxy;

R

30 through R 33 are independently selected from the group consisting of: OH; alkyl; aryl and arylalkyl;

R

50 is selected from the group consisting of: alkyl; heteroaryl; substituted heteroaryl and amino; wherein said substituents on said substituted R 5 0 groups are independently selected from the group consisting of: alkyl; halogen; and -OH; a is selected from the group consisting of: heteroaryl; substituted heteroaryl and (3) amino; R 5 1 is selected from the group consisting of: and alkyl.

In one embodiment, the compound may have any of the structures shown in Figures 6.

In another embodiment, the compound may have any of the structures shown in Figure 7.

In another aspect, the invention provides a method of treating a synucleinopathic subject by administering a farnesyl transferase inhibitor compound of the formula: 135

O

ID

00 0 2 NO RX X3 R, y1 N NR 1 9

R

20 or a stereoisomeric form, or a pharmaceutically acceptable acid or base addition salt form thereof, in a therapeutically effective amount, wherein: A represents N or N-oxide; X represents N, CH or C, such that when X is N or CH, there is a single bond to carbon atom 11 as represented by the solid line; or when X is C, there is a double bond to carbon atom 11, as represented by the solid and dotted lines; X' and X 2 are independently selected from bromo or chloro, and X 3 and X 4 are independently selected from hydrogen, bromo or chloro provided that at least one of X 3 and X 4 is hydrogen; Y' and Y2 are independently selected from hydrogen or alkyl; Z is =O or=S;

R

5

R

6

R

7 and R 8 each independently represents hydrogen, CF 3

COR

0 alkyl or aryl, and further wherein R 5 may be combined with R 6 to represent =O or =S and/or R 7 may be combined with R 8 to represent =0 or =S;

R

1 0

R

19 and R 20 independently represent hydrogen, alkyl, alkoxy, aryl, aralkyl, heteroaryl, heteroarylalkyl, cycloalkyl, cycloalkylalkyl, heterocycloalkyl and heterocycloalkylalkyl, with the proviso that R 1 9 and R 20 are not both hydrogen; v is zero, 1, 2 or 3; and w is zero or 1.

In one embodiment, there may be a single bond at carbon atom 11, X is CH, Z is =0 and

R

5 R6 R 7 and R 8 are hydrogen. In one embodiment, X' is bromo, X 2 is chloro, X 3 is bromo

ID

S and X 4 is hydrogen. In one embodiment, Z is v is 1, w is 1, and Y' and Y 2 are hydrogen.

In one embodiment, R 1 9 and R 20 are independently selected from hydrogen, aryl and S heterocycloalkyl wit h the proviso that R 1 9 and R 2 0 are not both hydrogen. In one embodiment, 00 the aryl group is substituted with alkoxy; and the heterocycloalkyl group is substituted with

COOR

1 0 wherein R' 1 is hydrogen or alkyl. In one embodiment, there is a single bond at carbon atom 11, X is CH, Z is R 5

R

6

R

7 and R 8 are hydrogen, X' is bromo, X 2 is chloro, X 3 is l bromo and X 4 is hydrogen, v is 1, w is 1, and Y' and Y 2 are hydrogen, R 1 9 and R 20 are c independently selected from hydrogen, aryl and heterocycloalkyl; wherein the aryl group is I substituted with alkoxy; and the heterocycloalkyl group is substituted with COORo 0 wherein O 10 R 0 is hydrogen or alkyl, with the proviso that R 1 9 and R 2 0 are not both hydrogen. In one embodiment, the compound may be any of the compounds shown in Figure 8. In another embodiment, the compound may be any of the compounds shown in Figure 9. In one embodiment, there is a single bond at carbon atom 11, X is CH, Z is =0 and R 5

R

6

R

7 and R 8 are hydrogen. In one embodiment, X' is bromo, X 2 is chloro, X 3 is bromo and X 4 is hydrogen.

In one embodiment, Z is v is 1, w is 1, and Y' and Y 2 are hydrogen. In one embodiment,

R'

9 and R 20 are independently selected from hydrogen, alkyl, aryl and heterocycloalkyl with the proviso that R 1 9 and R 20 are not both hydrogen. In one embodiment, the alkyl group is substituted with -OR' 0 alkoxy, -OCOR' 0

-CONR'O°R

2 or -COOR 1 0 wherein R' 1 and R 1 2 are independently selected from hydrogen, alkyl or alkoxy; the aryl group is substituted with alkoxy; and the heterocycloalkyl group is substituted with -COOR I 0 wherein R 10 is hydrogen or alkyl. In one embodiment, there is a single bond at carbon atom 11, X is CH, Z is 0, R 5

R

6

R

7 and R 8 are hydrogen, X' is bromo, X 2 is chloro, X 3 is bromo and X 4 is hydrogen, v is 1, w is 1, and Y' and Y 2 are hydrogen, R 1 9 and R 2 0 are independently selected from hydrogen, alkyl, aryl and heterocycloalkyl, wherein the alkyl group is substituted with -OR 1 0 alkoxy, OCOR'O, -CONRi'R 1 2 or -COOR 1 0 wherein R 0 and R 1 2 are independently selected from hydrogen, alkyl or alkoxy; the aryl group is substituted with alkoxy; the heterocycloalkyl group is substituted with -COOR 10 wherein R' 0 is hydrogen or alkyl, with the proviso that R 19 and

R

20 are not both hydrogen.

In another aspect, the invention provides a method of treating a synucleinopathic subject by administering a farnesyl transferase inhibitor compound of the formula: O R1 0

R

2 00

N

VV\ R3

O

IV

N

Z1 n or a stereoisomeric form, or a pharmaceutically acceptable acid or base addition salt form thereof, in a therapeutically effective amount, wherein: R and R 2 are independently selected from halo; R' and R 3 are independently selected from the group consisting of H and halo, provided that at least one of R' and R 3 is H; W is N, CH or C, when the double bond is present at the C-11 position;

R

4 is N n3 R n 2 Z2 or R 5

R

5 is R6 \N R6 R XN= XN x N R7 O O

I

R

6

R

6 and R 7 are independently selected from the group consisting of H, alkyl, substituted alkyl, acyl, aryl, aralkyl, heterocycloalkyl and heteroaryl; X is =0 or=S; Z and Z 2 are independently =0 or =S; n and n 3 are independently 0, 1 or 2; and ni and n2 are independently 0 or 1.

In one embodiment, X is =0 and R 6 and R 7 are each hydrogen. In one embodiment, n is 1 and n 3 is 0 or 1. In one embodiment, R is bromo and R 2 is chloro or bromo. In one embodiment, R is bromo, R 2 is chloro or bromo, R' is H, and R 3 is chloro or bromo. In one embodiment, R is bromo, R 2 is chloro or bromo, R 3 is H, and R' is chloro or bromo. In one embodiment, the compound may any one of the following: In another aspect, the invention provides a method of treating a synucleinopathic subject by administering a farnesyl transferase inhibitor compound of the formula: Z/

R

46 R21 or a stereoisomeric form, or a pharmaceutically acceptable acid or base addition salt form thereof, in a therapeutically effective amount, wherein: a represents N and the remaining b, c and d groups represent CR' or CR 2 R' is selected from H or halo;

R

2 is selected from NO 2 Br, Cl or I;

R

3 is Cl; O4

SR

4 is H or halo; R_ R 5

R

6

R

7 and R 8 are H; O the dotted line between carbon atoms 5 and 6 represents an optional double bond, such 00 that when a double bond is present, A and B independently represent H, and when no double bond is present between carbon atoms 5 and 6, A and B each independently represent H 2

R

20 and R 2 1 are independently selected from H or alkyl; 46

SR

46 is selected from: pyridyl, pyridyl N-oxide or piperidine Ring V:

(N

SN-R

50 wherein R 50 represents alkyl, alkylcarbonyl, alkyloxycarbonyl, haloalkyl, or wherein R' 1 is H or alkyl; and Z represents O.

In one embodiment, R' is H. In one embodiment, R 2 is selected from Br, Cl or I. In one embodiment, R 2 is Br at the C-3 position. In one embodiment, R 2 is Br at the C-3 position and

R

3 is at the C-8 position. In one embodiment, both R 20 and R 2 1 are hydrogen, or both R 2 0 and

R

21 are alkyl. In one embodiment, both R 20 and R 21 are hydrogen. In one embodiment, R 46 is 3-pyridyl, 4-pyridyl, 3-pyridyl N-oxide, 4-pyridyl N-oxide, 4-N-methyl piperidinyl, 3-Nmethylpiperidinyl, 4-N-acetylpiperidinyl or 3-N-acetylpiperidinyl. In one embodiment, R 46 is 3-pyridyl, 4-pyridyl, 3-pyridyl N-oxide, or 4-pyridyl N-oxide. In one embodiment, R 46 is 4pyridyl or 4-pyridyl N-oxide. In one embodiment, the compound may be any of the compounds shown in Figure 10. In another embodiment, the compound may be any of the compounds shown in Figure 11. In one embodiment, the compound is of the formula:

IND

o A /B

R

1 O R

R

R4is H or halo;

N

IN R5R s R

R

6 R and R are H; the dotted line between carbon atoms 5 and 6 represents an optional double bond, such that when a double bond is present, A and B independently represent H, and when no double bond is present between carbon atoms 5 and 6, A and B each independently represent H 2 S 2 R 20 Sand 21 are wherein: R' is selected from H or halo;

R

2 is selected from -CH3pyridyl, pyridyl N-oxide, triazolyl, -N-methylpiperazinyl, wherein t is 0, or 2, or piperidine Ring V: R4 is H or halo;

R

5

R

6

R

7 and R 8 are H; he dotted line between carbon atoms 5 and 6 represents alky, alkycarbonyl, alkoxycarbonyl, hooal double bond, such C()NH(at when a double bond is H or alkyl; and B independently represent H, and when no double bond is present between carbon atoms 5 and 6, A and B each independently represent H2;

R

20 and R 2 1 are H;

R

46 is selected from: pyridyl, pyridyl N-oxide, triazolyl, 1-N-methylpiperazinyl, wherein t is 0, 1 or 2, or piperidine Ring V: (L N-R 50 wherein R 50 represents alkyl, alkylcarbonyl, alkoxycarbonyl, haloalkyi, or C(0)NH(R 10 wherein R 10 is H or alkyl; and

ID

O Z represents O.

In one embodiment, R' is H. In one embodiment, R 2 is selected from Br. In one Sembodiment, R 2 is Br and R is at the C-8 position. In one embodiment, R 46 is selected from 3- 00 pyridyl, 4-pyridyl, 3-pyridyl N-oxide, 4-pyridyl N-oxide, 4-N-methyl piperidinyl, 3-Nmethylpiperidinyl, 4-N-acetylpiperidinyl or 3-N-acetylpiperidinyl. In one embodiment, R 4 6 is selected from: 3-pyridyl, 4-pyridyl, 3-pyridyl N-oxide, or 4-pyridyl N-oxide. In one embodiment, R 46 is selected from 4-pyridyl or 4-pyridyl N-oxide. In one embodiment, the c compound may be any of the compounds shown in Figure 12, Figure 13, or Figure 14.

In one aspect, the compound may have the formula: A ,B C R 1 6\ R3 R2 \-R4 R7

R

6 R8 L R2 0 Z4R 4 6 R21 wherein:

R

1 is selected from H or halo;

R

2 is C1;

R

3 is CI;

R

4 is H or halo;

R

5

R

6

R

7 and R 8 are H; the dotted line between carbon atoms 5 and 6 represents an optional double bond, such that when a double bond is present, A and B independently represent H, and when no double bond is present between carbon atoms 5 and 6, A and B each independently represent H2;

R

20 and R 2 1 are H;

R

46 is selected from: 4-pyridyl N-oxide, 4-pyridyl or piperidine Ring V: Swherein R 50 represents alkyl, alkylcarbonyl, alkyloxycarbonyl, haloalkyl, or

C(O)NH(R'

0 wherein R' 1 is H or alkyl; and O Z represents O.

00 In one embodiment, R' is H. In one embodiment, R 3 is at the C-8 position. In one embodiment, R 46 is 4-pyridyl N-oxide, 4-N-methyl piperidinyl, or 3-N-methylpiperidinyl. In one embodiment, the compound may have any structure shown in Figure In one aspect, the compound may be of the formula: a A B

I

ID

O wherein: a represents N and the remaining b, c and d groups represent CR' or CR 2 R' and R 2 are independently selected from H, halo, CF 3 lower alkyl or benzotriazol-1- O yloxy; 00 R 3 and R 4 are independently selected from H or halo;

R

5

R

6

R

7 and R 8 are H; the dotted line between carbon atoms 5 and 6 represents an optional double bond, such Sthat when a double bond is present, A and B independently represent H, and when no c double bond is present between carbon atoms 5 and 6, A and B each independently I represent H 2 R25 0 10 R represents pyridyl, pyridyl N-oxide, N-methyl-piperidinyl or phenyl;

R

48 represents H or alkyl; and Z represents O.

In one embodiment, R' is Cl or H; and R 2 is H, Cl or Br. In one embodiment, R 3 is Cl.

In one embodiment, R 25 represents phenyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, 2-pyridyl N-oxide, 3-pyridyl N-oxide, or 4-pyridyl N-oxide. In one embodiment, R 48 represents H or methyl. In one embodiment, R 25 represents phenyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, 2-pyridyl N-oxide, 3pyridyl N-oxide, or 4-pyridyl N-oxide; and R 48 represents H or methyl. In one embodiment, R' is Cl or H; R 2 is Br, CI, or I; R 3 and R 4 independently represent H or halo; R 25 represents phenyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, 2-pyridyl N-oxide, 3-pyridyl N-oxide, or 4-pyridyl Noxide; and R 48 represents H or methyl. In one embodiment, R 3 is Cl at the C-8 position and R 4 is H. In one embodiment, the compound may have any structure shown in Figure 16, Figure 17, or Figure 18.

In one aspect, the compound may be of the formula:

I

I

0 2

N

R

6 zR 0 2

N

wherein: R' is selected from H or halo;

R

3 is Cl;

R

4 is H or halo; the dotted line between carbon atoms 5 and 6 represents an optional double bond, such 0 that when a double bond is present, A and B independently represent H, and when no double bond is present between carbon atoms 5 and 6, A and B each independently represent H 2 and

R

65 represents H or OR 66 wherein R 66 represents alkyl.

In one embodiment, the compound is: 0 2

N-

or

-CI

In another aspect, the invention provides a method of treating a synucleinopathic subject by administering a farnesyl transferase inhibitor compound having a formula shown in Figure 19, or a stereoisomeric form, or a pharmaceutically acceptable acid or base addition salt form thereof, in a therapeutically effective amount.

In another aspect, the invention provides a method of treating a synucleinopathic subject by administering a farnesyl transferase inhibitor having a formula shown in Figure 20, or a stereoisomeric form, or a pharmaceutically acceptable acid or base addition salt form thereof, in a therapeutically effective amount. In one embodiment, the compound is: 147 0 000 N N NH 2 racemic, Bor (+)-enantiomer.

In another aspect, the invention provides a method of treating a synucleinopathic subject by administering a therapeutically effective amount of a stereoisomeric form, or a pharmaceutically acceptable acid or base addition salt form of a farnesyl transferase inhibitor compound of the formula: In another aspect, the invention provides a method of treating a synucleinopathic subject, by administering a therapeutically effective amount of a stereoisomeric form, or a pharmaceutically acceptable acid or base addition salt form of a farnesyl transferase inhibitor compound of the formula: (+)-enantiomer.

ID

In another aspect, the invention provides a method of treating a synucleinopathic subject by administering a therapeutically effective amount of a stereoisomeric form, or a O pharmaceutically acceptable acid or base addition salt form of a farnesyl transferase inhibitor 00 compound of the formula: t",,C C^ .Br 0 N N NH2 In another aspect, the invention provides a method of treating a synucleinopathic subject by administering a farnesyl transferase inhibitor compound of the formula:

(R

8 )r 9 R2 R 3 Ia Wl(CR 2)p N N V- A(CR1a2)A2(CR 2)n t (CR 2)p N N

R

4 v or a stereoisomeric form, or a pharmaceutically acceptable acid or base addition salt form thereof, in a therapeutically effective amount, wherein:

R

1a and Rib are independently selected from: a) hydrogen, b) aryl, heterocycle, C 3 -Clo cycloalkyl, C 2

-C

6 alkenyl, C 2

-C

6 alkynyl, R 10 R" S(O)m

R

1

C(O)NR

i0

(R'I)

2 CN, NO 2

(R"O)

2

N-C(NR'

0

R

1 0

R

1 0

N

3 N(Ri 0 or R" OC(O)NR 0 c) unsubstituted or substituted Ci -C 6 alkyl wherein the substitutent on the substituted Ci

C

6 alkyl is selected from unsubstituted or substituted aryl, heterocyclic, C 3 -Clo cycloalkyl,

C

2

-C

6 alkenyl, C 2

-C

6 alkynyl, R 10 R" R' 0 C(O)NR' (R' 0 2 N-C(O) CN,

(R'

0 2

N-C(NR'

0

R'

0

R'

0

N

3

-N(R'

0 2 and R" OC(O)-NR' 0 o) R 2 and R 3 are independently selected from: H; unsubstituted or substituted C 1 8 alkyl, 00 unsubstituted or substituted C 2 8 alkenyl, unsubstituted or substituted C 2 8 alkynyl, unsubstituted or substituted aryl, unsubstituted or substituted heterocycle, Y NRIR 7

OR'

0 or 0 IND wherein the substituted group is substituted with one or more of:- 1) aryl or heterocyci, unsubstituted or substituted with: a) C14 alkyl, b) (CH 2 )p OR 6 c) (CH 2 )p NR 6 R d) halogen, e) CN, 2) C 3 6 cycloalkyl, 3)OR 6 4) SR a, S(O)R a, SO 2

R

6 -NR R'7 6) 0

R

6 I IY NR 7 R 7 a 7) 0 0 y NR 6 R 7 8) 0

IO

-0 NR 6 O 9) 0 00 NR 6

R

7 0 o 11) SO 2

-NR

6

R

7 CM R 6 12) -N-SO2-R 6 a Y R 6 13) 0

YOR

6 14) O

N

3 or 16) F; or

R

2 and R 3 are attached to the same C atom and are combined to form -(CH 2 wherein one of the carbon atoms is optionally replaced by a moiety selected from: 0, S(O)m, and N(COR'O)-;

R

4 and R 5 are independently selected from H and CH 3 and any two of R 2

R

3

R

4 and R 5 are optionally attached to the same carbon atom;

R

6

R

7 and R 7 a are independently selected from: H; C-4 alkyl, C3- 6 cycloalkyl, heterocycle, aryl, aroyl, heteroaroyl, arylsulfonyl, heteroarylsulfonyl, unsubstituted or substituted with: a) Ci-4 alkoxy, b) aryl or heterocycle, c) halogen, d) HO, R e) 0 f) SO 2 or g) N(R 0 2 or R_ 6 and R 7 may be joined in a ring; o R 7 and R 7 may be joined in a ring; 00 R 6 is selected from: C 1 4 alkyl, C 3 6 cycloalkyl, heterocycle, aryl, unsubstituted or substituted with: a) C14 alkoxy, b) aryl or heterocycle, c) halogen, d) HO, e) 0 f) SO 2 or R 8 is independently selected from: a) hydrogen, b) aryl, heterocycle, C 3 -CIO cycloalkyl, C 2

-C

6 alkenyl, C 2

-C

6 alkynyl, perfluoroalkyl, F, CI, Br, R' 0 R' S(O)m, RIO C(O)NR' 0

(R"

0 2

R'

0 2

N-C(NR'

0

CN,

NO

2 RIO RIO N 3

N(R'

0 2 or R" OC(O)NR' 0 and C) CI -C 6 alkyl unsubstituted or substituted by aryl, cyanophenyl, heterocycle, C 3

-CIO

cycloalkyl, C 2

-C

6 alkenyl, C 2

-C

6 alkynyl, perfluoroalkyl, F, Cl, Br, R 10 S(O)m

R'

0 (RIN) R' 0 2 CN, RIO R' 0

N

3 or R' 0

C(O)NH--;

R

9 is selected from: a) hydrogen, b) C 2

-C

6 alkenyl, C 2

-C

6 alkynyl, perfluoroalkyl, F, Cl, Br, RIO R" S(O)m' RIO

C(O)NR'

0

(R'

0 2

R'

0 2

N-C(NR'

0 CN, NO 2

R'

0 RIO N 3 NR"2,or R" OC(O)NR' 0 and C) CI -C 6 alkyl unsubstituted or substituted by pertluoroalkyl, F, CI, Br, R1 0

R"

RIO C(O)NR' 0

(R'

0 2

R'

0 2

N-C(NR'

0 CN, RIO RIO

N

3

N(R'

0 2 or OC(O)NR 1 0 RIO is independently selected from hydrogen, C, -C 6 alkyl, benzyl and aryl; R' 1is independently selected from C, -C 6 alkyl and aryl;

ID

SA' and A 2 are independently selected from: a bond, CH=CH--, C.tbd.C--,

C(O)NR

1 0

NR

1 0 O, N(R 0 o -S(0) 2 N(RIo)S(0) 2 or S(O)m; 00 V is selected from: a) hydrogen, b) heterocycle, c) aryl, d) CI -C 20 alkyl wherein from 0 to 4 carbon atoms are replaced with a heteroatom selected from O, S, and N, and e) C 2

-C

20 alkenyl, \provided that V is not hydrogen if A' is S(O)m and V is not hydrogen if A' is a bond, n c is 0 and A 2 is S(O)m I W is a heterocycle; X is CH2 or S(=O)m Y is unsubstituted or substituted aryl or unsubstituted or substituted heterocycle, wherein the substituted aryl or substituted heterocycle is substituted with one or more of: 1) C-4 alkyl, unsubstituted or substituted with: a) C-4 alkoxy, b) NR 6

R

7 c) C 3 -6 cycloalkyl, d) aryl or heterocycle, e) HO, f) S(O)m R 6 a or g) C(O)NR 6

R

7 2) aryl or heterocycle, 3) halogen, 4) OR 6 5) NR 6

R

7 6) CN, 7) NO 2 8) CF 3 9) R 6 a, 10)

C(O)NR

6

R

7 or 11) C 3

-C

6 cycloalkyl m is 0, 1 or 2; n is 0, 1, 2, 3 or 4; p is 0, 1, 2, 3 or 4; q is I or 2; r is 0 to 5, provided that r is 0 when V is hydrogen; s is 0 or 1; t is 0 or 1; and u is 4 or In one embodiment, the compound may be of the formula: (R)r (R9 R 2

R

3 V- A' (CR22)nA2(CR2)n-- W t (CR2)p N Nt j Y

R

4 or a stereoisomeric form, or a pharmaceutically acceptable acid or base addition salt form thereof, in a therapeutically effective amount, wherein:

R

la is independently selected from: hydrogen or Ci -C 6 alkyl; Rlb is independently selected from: a) hydrogen, b) aryl, heterocycle, cycloalkyl, R' 0 2 or C 2

-C

6 alkenyl, c) unsubstituted or substituted C, -C 6 alkyl wherein the substitutent on the substituted C,

C

6 alkyl is selected from unsubstituted or substituted aryl, heterocycle, cycloalkyl, alkenyl,

RIO

0 and N(R' 0 R 3 R 4 and R 5 are independently selected from H and CH 3 Y

NRR

7

R

2 is H; 0 or C 15 alkyl, unbranched or branched, unsubstituted or substituted with one or more of: 1) aryl, 2) heterocycle, 3) OR 6 4) SR a, S0 2 R~a or b and any two of R 2 R 3 R 4 and R 5 are optionally attached to the same carbon atom; R 6 R 7 and R' are independently selected from: H; CIA alkyl, C 3 6 cycloalkyl, aryl, heterocycle, unsubstituted or substituted with: a) CIAalkoxy, b) halogen, or c) aryl or heterocycle; R 6 a is selected from: C IA alkyl or C 3 6 cycloalkyl, unsubstituted or substituted with: a) C IA alkoxy, b) halogen, or c) aryl or heterocycle; R 8 is independently selected from: a) hydrogen, b) CI -C 6 alkyl, C 2

-C

6 alkenyl, C 2

-C

6 alkynyl, C 1

-C

6 perfluoroalkyl, F, Cl, RIO RIO

C(O)NR'

0 CN, NO 2

(R'

0 2

N-C(NR'

0 RIO RIO N(R' 0 2 or R

OC(O)NR'

0 and C) C 1

-C

6 alkyl substituted by C, -C 6 perfluoroalkyl, RIO RIO C(O)NR' 0

(R'

0 2

N-

C(NR'

0 RIO RIO N(R'% 2 or R" OC(O)NR' 0

OD

SR

9 is selected from: a) hydrogen, b) C 2

-C

6 alkenyl, C 2

-C

6 alkynyl, Ci -C 6 perfluoroalkyl, F, CI, R 10 R" S(O)m R 10 00 C(O)NR' 1 CN, NO 2

(R'

0 2

N-C(NR'

0

R

i 0 R'O N(Ri') 2 or R

II

OC(O)NR

10 and c) CI -C 6 alkyl unsubstituted or substituted by Ci -C 6 perfluoroalkyl, F, Cl, R'O R" SS(O)m R 1 0

C(O)NR

1 0 CN, (R'I)2 N-C(NRIo)--, R

I

o R

I

o N(Ri') 2 or R" OC(O)NR

SR

1 0 is independently selected from hydrogen, Ci -C 6 alkyl, benzyl and aryl; 0 10 R" is independently selected from Ci -C 6 alkyl and aryl; A' and A 2 are independently selected from: a bond, CH=CH--, C.tbd.C--,

C(O)NR

1 O, N(R 10 or S(O)m; V is selected from: a) hydrogen, b) heterocycle selected from pyrrolidinyl, imidazolyl, pyridinyl, thiazolyl, pyridonyl, 2oxopiperidinyl, indolyl, quinolinyl, isoquinolinyl, and thienyl, c) aryl, d) CI -C 20 alkyl wherein from 0 to 4 carbon atoms are replaced with a a heteroatom selected from O, S, and N, and e) C 2

-C

20 alkenyl, and provided that V is not hydrogen if A' is S(O)m and V is not hydrogen if A' is a bond, n is 0 and A 2 is S(O)m W is a heterocycle selected from pyrrolidinyl, imidazolyl, pyridinyl, thiazolyl, pyridonyl, 2oxopiperidinyl, indolyl, quinolinyl, or isoquinolinyl; X is CH2 or Y is mono- or bicyclic aryl, or mono- or bicyclic heterocycle, unsubstituted or substituted with one or more of: a) C-4 alkyl, b) C-4 alkoxy, c) halogen, or d) NR 6

R

7 m is 0, 1 or 2; n is 0, 1, 2, 3 or 4; p is 0, 1, 2, 3 or 4; r is 0 to 5, provided that r is 0 when V is hydrogen; s is 0 or 1; and t is 0 or 1.

In another aspect, the invention provides a method of treating a synucleinopathic subject by administering a farnesyl transferase inhibitor compound of the formula:

ID

G

0 R2 G

S(R

8 )r (R 9

R

O V- A(CR1a2)nA2(CRa2)n W- (CRb2)p N N- Z 00 t X R4/ 0 or a stereoisomeric form, or a pharmaceutically acceptable acid or base addition salt form C thereof, in a therapeutically effective amount, 0 5 wherein: NC R la and R'b are independently selected from: a) hydrogen, b) aryl, heterocycle, C 3 -Clo cycloalkyl, C 2

-C

6 alkenyl, C 2

-C

6 alkynyl, R' i R" S(O)m

R

1 0

C(O)NR'

1

CN(R'

0 2

R'

0 2

N-C(NRI

0 CN, NO 2

R'

0

R

1 0

N

3

N(R

0 2 or R' I OC(O)NR c) unsubstituted or substituted C| -C 6 alkyl wherein the substitutent on the substituted Ci

C

6 alkyl is selected from unsubstituted or substituted aryl, heterocyclic, C 3 -Clo cycloalkyl,

C

2

-C

6 alkenyl, C 2

-C

6 alkynyl, R 1 0 R" S(O)m R1 0 C(0)NR 0

(RIO)

2

RIO

2 N-C(NRO) CN, R 1 0

R

I0

N

3

N(RI)

2 and R" OC(O)--NR 0

R

2 and R 3 are independently selected from: H; unsubstituted or substituted C.I- alkyl, unsubstituted or substituted C2-8 alkenyl, unsubstituted or substituted C2- 8 alkynyl, unsubstituted or substituted aryl, unsubstituted or substituted heterocycle,

NR

6

R

7

OR

6 0 or 0 wherein the substituted group is substituted with one or more of: 1) aryl or heterocycle, unsubstituted or substituted with: a) C-4 alkyl, b) (CH 2 )p OR 6 c) (CH 2 )p NR 6

R

7 d) halogen, e) CN, 2) C 3 6 cycloalkyl, 3) OR 6 7.

4) SR S(O)R a, SO 2

R

6 -NR R" 6) 0 R6 7

R

NR 6 R 7

NR

6 y ~NRR 7 0 -S0 2

-NR

6

R

7 14)

N

3 or 16) F; or

SR

2 and R 3 are attached to the same C atom and are combined to form (CH 2 )u wherein one N of the carbon atoms is optionally replaced by a moiety selected from: O, S(O)m, NC(O)-, o and -N(CORio)-; 00 R 4 is selected from H and CH3; and any two of R 2

R

3 and R 4 are optionally attached to the same carbon atom;

SR

6

R

7 and R 7a are independently selected from: H; CI-4 alkyl, C 3 6 cycloalkyl, heterocycle, aryl, aroyl, heteroaroyl, arylsulfonyl, heteroarylsulfonyl, unsubstituted or substituted with: a) CI-4 alkoxy, Sb) aryl or heterocycle, 0 10 c) halogen, d) HO, YR11 e) 0 f) SO 2 or g) N(R' 0 2 or

R

6 and R 7 may be joined in a ring;

R

7 and R 7 a may be joined in a ring;

R

6 a is selected from: C14 alkyl, C3- 6 cycloalkyl, heterocycle, aryl, unsubstituted or substituted with: a) C.4 alkoxy, b) aryl or heterocycle, c) halogen, d) HO,

Y"R"

e) 0 f) -SO 2 or g) N(R'0)2

R

8 is independently selected from: a) hydrogen, b) aryl, heterocycle, C 3 -CIO cycloalkyl, C 2

-C

6 alkenyl, C 2

-C

6 alkynyl, perfluoroalkyl, N Cl, Br, R'00, R" R' 0 C(O)NR (R' 0 2 R 0 2 CN, NO,, o R' 0

R'

0

N

3 -N(R 0)2, or R"OC(O)NR' 0 and 00 C) CI -C 6 alkyl unsubstituted or substituted by aryl, cyanophenyl, heterocycle, C 3

-CI

0 cycloalkyl, C 2

-C

6 alkenyl, C 2

-C

6 alkynyl, perfluoroalkyl, F, Cl, Br, R1 0 RIO C(O)NH-, (R" 0 2

R'

0 2

N-C(NR'

0 CN, RIO R" 0

N

3 or R' C(O)NH-;

R

9 is selected from: IND a) hydrogen, b) alkenyl, alkynyl, perfluoroalkyl, F, Cl, Br, R' R' RI C(O)NRI'- (R1 0 2

R'

0 2

N-C(NR'

0 CN, NO 2

R"

0

R'

0

N

3

N(R'

0 2 or R" OC(0)NR' 0 and C) CI -C 6 alkyl unsubstituted or substituted by perfluoroalkyl, F, CI, Br, R1 0

R"

S(O)m, R' 0

C(O)NR'

0

(R'

0 2

R'

0 2

N-C(NR'

0 CN, R' 0

R'

0

N

3

N(R'

0 2 or R" 1

OC(O)NR

10 R1 0 is independently selected from hydrogen, C, -C 6 alkyl, benzyl and aryl; R1 1 is independently selected from C I -C 6 alkyl and aryl; Al and A 2are independently selected from: a bond, CH=CH--, C.tbd.C--,

C(O)NR'

0

-NR'

0 0, -N(R' 0 S(0) 2

N(R'

0

N(R'

0

)S(O)

2 or S(O)mn; G is H 2 orO0; V is selected from: a) hydrogen, b) heterocycle, c) aryl, d) C, -C 20 alkyl wherein from 0 to 4 carbon atoms are replaced with a a heteroatoin selected from 0, S, and N, and e) C 2

-C

20 alkenyl, provided that V is not hydrogen if A' is S(O),m and V is not hydrogen if A' is a bond, n is 0 and A 2is W is a heterocycle; X is CH 2 or S(=O)m Z is a unsubstituted or substituted group selected from aryl, heteroaryl, arylmethyl, heteroarylmethyl, arylsulfonyl, heteroarylsulfonyl, wherein the substituted group is substituted with one or more of the following: 160

ID

O 1) C-4 alkyl, unsubstituted or substituted with: a) Ci 4 alkoxy, b) NR 6

R

7 c) C 3 6 cycloalkyl,

C

d) aryl or heterocycle, e) HO, f) S(O)m R 6 a or g) C(O)NR 6

R

7 2) aryl or heterocycle, 3) o halogen, 4) OR 6 5) NR 6

R

7 6) CN, 7) NO 2 8) CF 3 9) S(O)m R 6a 10) C(O)NR 6

R

7 or O0 11) C 3

-C

6 cycloalkyl; m is 0, 1 or 2; n is 0, 1, 2, 3 or 4; p is 0, 1,2, 3 or 4; q is 1 or 2; r is 0 to 5, provided that r is 0 when V is hydrogen; s is 0 or 1; t is 0 or 1; and u is 4or SIn one embodiment, the compound may be of the formula:

G

(R

8 )r

(R

9

AI(CR

1 a2)nA2(CR2)n W (CRb 2 N N- Z t X R4 s or a stereoisomeric form, or a pharmaceutically acceptable acid or base addition salt form thereof, in a therapeutically effective amount, wherein: Ri a is independently selected from: hydrogen or Ci -C 6 alkyl; Rlb is independently selected from: a) hydrogen, b) aryl, heterocycle, cycloalkyl, R 1 0

N(R'

0 2 or C 2

-C

6 alkenyl, c) unsubstituted or substituted C 1

-C

6 alkyl wherein the substitutent on the substituted Ci

C

6 alkyl is selected from unsubstituted or substituted aryl, heterocycle, cycloalkyl, alkenyl,

R'

i and N(R' 0 2

R

3 and R 4 are independently selected from H and CH 3 Y NR 6

R

7 R is H; 0 or C 1 -5 alkyl, unbranched or branched, unsubstituted or substituted with one or more of: 1 aryl, 2) heterocycle, 3) OR 6 4) SR 6 a, SO 2

R

6 a, or Y ~NR'R 7 0 00 and any two of R 2 R R 4 and R. are optionally attached to the same carbon atom; R 6 R 7 and R 7 are independently selected from: H; C 14 alkyl, C 3 6 cycloalkyl, aryl, heterocycle, unsubstituted or substituted with: a) C1 4 alkoxy, b) halogen, or IND c) aryl or heterocycle;

R

6 is selected from:

C

14 alkyl or C 3 6 cycloalkyl, unsubstituted or substituted with: a) C- 4 alkoxy, b) halogen, or c) aryl or heterocycle; R 8 is independently selected from: a) hydrogen, b) C, -C 6 alkyl, C 2

-C

6 alkenyl, C 2

-C

6 alkynyl, C, -C 6 perfluoroalkyl, F, ClI, R1 0 R1 0

C(O)NR'

0 CN, NO 2

(R'

0 2

N-C(NR'

0

R'

0

R'

0

N(R'

0 2 or R

OC(O)NR'

0 and C) CI -C 6 alkyl substituted by C, -C 6 perfluoroalkyl, R' 0

R'

0

C(O)NR'

0 (R 10)2 N-

C(NR'

0

R'

0

R'

0

N(R'

0 2 or R" OC(O)NR' 0 R9 is selected from: a) hydrogen, b) C 2

-C

6 alkenyl, C 2

-C

6 alkynyl, C, -C 6 perfluoroalkyl, F, CI, R 10 R" S(O)m, R

C(O)NR'

0 CN, NO 2

(R'

0 2

N-C(NR

1 0

R'

0

R'

0

N(R'

0 2 or R

OC(O)NR'

0 and C) CI -C 6 alkyl unsubstituted or substituted by C 1

-C

6 perfluoroalkyl, F, Cl, RIO RI I

R'

0

C(O)NR'

0 CN, (RIN) N-C(NR' 0

R'

0

R'

0

N(R'

0 2 or R" 0C(O)NR"

R

10 is independently selected from hydrogen, C 1

-C

6 alkyl, benzyl and aryl; R"1 is independently selected from C I -C 6 alkyl and aryl; Al and A2 are independently selected from: a bond, CH=CH--, C.tbd.C--,

C(O)NR'

0 0, -N(R' 0 or S(O)m,;

ID

V is selected from: Sa) hydrogen, O b) heterocycle selected from pyirolidinyl, imidazolyl, pyridinyl, thiazolyl, pyridonyl, 2- 00 oxopiperidinyl, indolyl, quinolinyl, isoquinolinyl, and thienyl, c) aryl, d) Ci -C 20 alkyl wherein from 0 to 4 carbon atoms are replaced with a a heteroatom selected 0 ffrom O, S, and N, and e) C 2

-C

20 alkenyl, and provided that V is not hydrogen if A' is S(O)m and V is not hydrogen if A is a bond, n is 0 and A 2 is S(O)m; G is H 2 or O; W is a heterocycle selected from pyrrolidinyl, imidazolyl, pyridinyl, thiazolyl, pyridonyl, 2oxopiperidinyl, indolyl, quinolinyl, or isoquinolinyl; X is CH 2 or Z is mono- or bicyclic aryl, mono- or bicyclic heteroaryl, mono- or bicyclic arylmethyl, mono- or bicyclic heteroarylmethyl, mono- or bicyclic arylsulfonyl, mono- or bicyclic heteroarylsulfonyl, unsubstituted or substituted with one or two of the following: 1) C-4 alkyl, unsubstituted or substituted with: a) CI4 alkoxy, b) NR 6

R

7 c) C 3 -6 cycloalkyl, d) aryl or heterocycle, e) HO, f) S(O)m R 6 or g) C(O)NR 6

R

7 2) aryl or heterocycle, 3) halogen, 4) OR 6 5) NR 6

R

7 6) CN, 7) NO 2 8) CF 3 9) S(O)m R 6 10) C(0)NR 6

R

7 or 11) C 3

-C

6 cycloalkyl; m is 0, 1 or 2; n is 0, 1, 2, 3 or 4; p is 0, 1, 2, 3 or 4; r is 0 to 5, provided that r is 0 when V is hydrogen; s is 0 or 1; t is 0 or 1; and u is 4 or provided that when G is H 2 and W is imidazolyl, then the substitutent (CRla 2 )n

A

2 (CRla 2 )n is not H and provided that when X is or S(=O)m then t is 1 and the substitutent (R 8 )r V-- A' (CRla 2 )n A 2 (CRla 2 )n is not H.

In another aspect, the invention provides a method of treating a synucleinopathic subject by administering a farnesyl transferase inhibitor compound of the formula: 8 )r R R 3 I A(CRa 2

)A

2 (CR a 2 )n W (CR 1 2 N N- Z F s G R4 S G

IO

or a stereoisomeric form, or a pharmaceutically acceptable acid or base addition salt form O thereof, in a therapeutically effective amount, 00 wherein: R a and RIb are independently selected from: a) hydrogen, S b) aryl, heterocycle, C 3 -CIO cycloalkyl, C 2

-C

6 alkenyl, C 2

-C

6 alkynyl, R 1 0 R" S(O)m

R

I 0 C(O)NR'° (RI)2 RI°2 N-C(NR' 0 CN, NO 2

RI

0

R

1 0 S, N 3 N(R'I)2 or R II OC(O)NR 0 10 c) unsubstituted or substituted CI -C 6 alkyl wherein the substitutent on the substituted CI

C

6 alkyl is selected from unsubstituted or substituted aryl, heterocyclic, C 3 -CIO cycloalkyl,

C

2

-C

6 alkenyl, C 2

-C

6 alkynyl, R 1 0 R" S(O)m R 1 0

C(O)NR'

I

(R'O)

2

R'

0 2 CN, RI 0

RI

0

N

3

N(RI

0 2 and R" OC(O)--NR i 0

R

2 and R 3 are independently selected from: H; unsubstituted or substituted CI.

8 alkyl, unsubstituted or substituted C2- 8 alkenyl, unsubstituted or substituted C2- 8 alkynyl,

SNR

6

R

7 unsubstituted or substituted aryl, unsubstituted or substituted heterocycle, O Y

OR

6 or 0 wherein the substituted group is substituted with one or more of: 1) aryl or heterocycle, unsubstituted or substituted with: a) Ci.

4 alkyl, b) (CH 2 )p OR 6 c) (CH 2 )p NR 6

R

7 d) halogen, e) CN, 2) C 3 6 cycloalkyl, 3) OR 6 4) SR 6a

S(O)R

6 a, SO 2

R

6 a, -NR6R 7 IND 164 0 6) 0

R

6 -N

NR

7

R

7 a ID7) 0 -0 NR 6

R

7 -0 Y NR 6 9) 0 Y

~NR

6

R'

10) 0 11) -S0 2

-NR

6

R

7

R

6 12 -N 4S0 2

R

6 a Y

R

6 13) 0 Y

~OR

6 14) 0 15) N 3 or 16) F; or R 2and R 3are attached to the same C atom and are combined to form (CH 2 wherein one of the carbon atoms is optionally replaced by a moiety selected from: 0, and N(COR'%-; R 4 is selected from H and CH 3 and any two of R 2 R 3 and R 4 are optionally attached to the same carbon atom; C.)6 7 7a C) R R and R are independently selected from: H; C 14 alkyl, C 3 6 cycloalkyl, heterocycle, 00 aryl, aroyl, heteroaroyl, arylsulfonyl, heteroarylsulfonyl, unsubstituted or substituted with: a) C14 ~alkoxy, b) aryl or heterocycle, c) halogen, d) HO, e) 0 f)J--SO 2 R"or g) N(R 1 0 2 ;or R 6 and R 7 may be joined in a ring; R 7 and R 7 a may be joined in a ring; R 6ais selected from: C 14 alkyl, C 3 6 cycloalkyl, heterocycle, aryl, unsubstituted or substituted with: a) C1 4 alkoxy, b) aryl or heterocycle, c) halogen, d) HO, e) 0 f) SO 2 R',or

R

8 is independently selected from: a) hydrogen, b) aryl, heterocycle, C 3 -CIO cycloalkyl, C 2

-C

6 alkenyl, C 2

-C

6 alkynyl, perfluoroalkyl, F, Cl, Br, RIO R' S(O)mn RIO C(O)NR' 0

(R'

0 2

R'

0 2 CN, NO 2 RIO RIO N 3

N(R'

0 2 or R' OC(O)NR 10 and C) C 1

-C

6 alkyl unsubstituted or substituted by aryl, cyanophenyl, heterocycle, C 3

-CIO

cycloalkyl, C 2

-C

6 alkenyl, C 2

-C

6 alkynyl, perfluoroalkyl, F, Cl, Br, RIO 0 R"

R'

0 (R'0)2 R' 0 2

N-C(NR'

0 CN, R" 0

R'

0

N

3 N(R 0)2, or R' 0

OC(O)NH--;

o R9 is selected from: 00 a) hydrogen, b) C 2

-C

6 alkenyl, C 2

-C

6 alkynyl, perfluoroalkyl, F, Cl, Br, R' 0 S(O)m' R' 0

C(O)NR'

0

(R'

0 2

R"

0 2

N-C(NR'

0 CN, NO 2

R'

0

R'

0

N

3 N(R or R" OC(O)NR' and C) C I -C 6 alkyl unsubstituted or substituted by perfluoroalkyl, F, Cl, Br, R' R" S(O)m' R0C(O)NR" R' 0 2 CN, R" 0

R'

0

N

3 010N(R 0)2, or R" OC(O)NR' 0 R1 0 is independently selected from hydrogen, C, -C 6 alkyl, benzyl and aryl; R" is independently selected from C, -C 6 alkyl and aryl; Al and A 2are independently selected from: a bond, CH=CH--, C.tbd.C--,

C(O)NR'

0

NR'

0 0, N(R1 0

S(O)

2

N(R'

0 or S(O)mn; G isO0; V is selected from: a) hydrogen, b) heterocycle, c) aryl, d) C, -C 20 alkyl wherein from 0 to 4 carbon atoms are replaced with a a heteroatomn selected from 0, S, and N, and e) C 2

-C

20 alkenyl, provided that V is not hydrogen if A' is S(O)m and V is not hydrogen if A' is a bond, n is 0 and A 2 is S(O)m W is a heterocycle; X is CH 2 or S(=O)m Z is a unsubstituted or substituted group selected from aryl, heteroaryl, arylmethyl, heteroarylmethyl, arylsulfonyl, heteroarylsulfonyl, wherein the substituted group is substituted with one or more of the following: 1).C, 4 alkyl, unsubstituted or substituted with: a) C14 alkoxy, b) NR 6 R C) C 3 6 cycloalkyl, d) aryl or heterocycle, e) HO, f) S(O)m R 6, or g) C(O)NR 6 R 7 2) aryl or heterocycle, 3) halogen, 4) OR 6 5) NR 6 R 7 6) CN, 7) NO 2 8) CF 3 9) -S(O)m R 6 a, 10) -C(O)NR 6 or 11) C 3

-C

6 cycloalkyl; m isO0, 1 or 2; nisO0, 1, 2, 3or4; pisO, 1, 2, 3 or 4; qis I or 2; ris 0to 5,provided that ris 0_ when Vis hydrogen;sis; t is 0or1; and uis 4or 0 In another aspect, the invention provides a method of treating a synucleinopathic subject by adrriinistering one or more of the following farnesyl transferase inhibitor compounds: 2(S)-Butyl-l1-(2,3-diaminoprop-I -naphthoyl)piperazine IND1 -(3-Amino-2-(2-naphthylmethylamino)prop- I -yl)-2(S)-butyl-4-( 1 -naphthoyl)piperazine C) 10 2(S)-Butyl- 1- I-(2-naphthylmethyl)]-4,5-dihydroimidazol }methyl-4-( 1naphthoyl)piperazine I I-Benzylimidazol)methyl]-2(S)-butyl-4-( 1 -naphthoyl)piperazine 1- 1-(4-Nitrobenzyl)imidazolyl]methyl)}-2(S)-butyl-4-(l1-naphthoyl)piperazine 1 -Acetamidomethylthio-2(R)-aminoprop- 1-yI)-2(S)-butyl-4-( 1 -naphthoyl)piperazine 2(S)-Butyl-l1-[2-( 1 -imidazolyl)ethyl]sulfonyl-4-( 1-naphthoyl)piperazine 2(R)-Butyl- 1 -imidazolyl-4-methyl-4-(1 -naphthoyl)piperazine 2(S)-Butyl-4-(1 -naphthoyl)-1I -(3-pyridylmethyl)piperazine 1 -2(S)-butyl-(2(R)-(4-nitrobenzyl)amino-3-hydroxypropyl)-4-( 1 -naphthoyl)piperazine I -(2(R)-Amino-3 -hydroxyheptadecyl)-2(S)-butyl-4-( I -naphthoyl)piperazine 2(S)-Benzyl- 1 -imidazolyl-4-methyl-4-( I -naphthoyl)piperazine I -(2(R)-Amino-3 -(3-benzylthio)propyl)-2(S)-butyl-4-(1 -naphthoyl)piperazine I -(2(R)-Amino-3 -[3-(4-nitrobenzylthio)propyl)))-2(S)-butyl-4-( I -naphthoyl)piperazine 2(S)-Butyl- I -[4-imidazolyl)ethyl]-4-(1 -naphthoyl)piperazine 2(S)-Butyl- I -[(4-imidazolyl)methyl]-4-(I -naphthoyl)piperazine 2(S)-Butyl- 1 -naphth-2-ylmethyl)- I H-imidazol-5-yl)acetyl]-4-( 1 -naphthoyl)piperazine 2(S)-Butyl- I -naphth-2-ylmethyl)- 1 H-imidazol-5-yl)ethyl]-4-( 1 -naphthoyl)piperazine 1 -(2(R)-Amino-3 -hydroypropyl)-2(S)-butyl-4-( I -naphthoyl)piperazine I -(2(R)-Amino-4-hydroxybutyl)-2(S)-butyl-4-( I -naphthoyl)piperazine I -(2-Amino-3-(2-benzyloxyphenyl)propyl)-2(S)-butyl-4-( 1 -naphthoyl)piperazine 1 -(2-Amino-3 -(2-hydroxyphenyl)propyl)-2(S)-butyl-4-( 1 -naphthoyl)piperazine 1 -[3-(4-imidazolyl)propyl]-2(S)-butyl-4-( 1 -naphthoyl)piperazine 2(S)-n-Butyl-4-( 1 -naphthoyl)- 1-ri 2(S)-n-Butyl-4-( 1 -naphthoyl)- I -[1I 2(S)-n-Butyl- 1 -(4-cyanobenzyl)imidazol-5-ylmethyl]-4-( I -naphthoyl)piperazine 168 INDnBtl -i-4mtoxbny~mdzi5ymty]-- nptolpprzn 2(S)-n-Butyl- 1-[rI -(3-methoy-benyl)imidazol-5-ylmethyl]-4-( -naphthoyl)piperazine 2()nBtl (-ehl2btnliidzl5ymty]40 nptoipprzn o 2(S)-n-Butyl- 1 -rI -(4-fluorobenzyl)imidazol-5-ylmethyl]-4-( I -naphthoyl)piperazine 00 2(S)-n-Butyl- I -(4-chlorobenzyl)imidazol-5-ylmethyl]-4-( I -naphthoyi)piperazine 1-[i1 -(4-Bromobenzyl)imidazol-5-ylmethyl]-2(S)-n-butyi-4-( 1 -naphthoyi)piperazine 1-[i1 -(4-Bromobenzyl)imidazol-5-ylmethyl]-2(S)-n-butyi-4-( 1 -naphthoyl)piperazine 2(S)-n-Butyl-4-( I -naphthoyl)- I -rI piperazine IND2(S)-n-Butyl- 1-[I -(4-methylbenzyl)imidazol-5-ylmethyl]-4-( 1 -naphthoyl)-piperazine C) 10 2(S)-n-Butyl- 1-fI -(3-methylbenzyl)imidazol-5-ylmethyl]-4-( I -naphthoyl)-piperazine i-ri1 -(4-Phenylbenzyl)imidazoi-5-ylmethyl]-2(S)-n-butyI-4-( 1 -naphthoyl)-piperazine 2(S)-n-Butyi-4-( I -naphthoyl)- 1-[i 2(S)-n-Butyl-4-( I -naphthoyi)- I-rI f r I -(4-cyanobenzyl)- 1 H-imnidazol-5-yilacetyl -2(S)-n-butyl-4-( I -naphthoyl)piperazine 5(S)-n-Butyi-1I -(2,3-dimethylphenyl)-4-(4-imidazolyimethyl)-piperazin-2-one 5(S)-n-Butyl-4-[ I-(4-cyanobenzyl)imidazol-5-ylmethyl]- 1 -(2,3-dimethylphenyl)piperazin- 2-one I-(4-Cyanobenzyl)imidazol-5-ylmethyl]- 1 -dimethylphenyl)-5(S)-(2methoxyethyl)p iperazi n-2 -one I -(3-Chlorophenyl)-4-[ 1-(4-cyanobenzyl)-5-imidazoiylmethyl]-5-[2- (methanesui fonyl)ethyi -2-piperazi none I -(3-Chlorophenyl)-4- i -(4-cyanobenzyl)-5-imidazolylmethyl]-5-r2- (ethanesulfonyl)ethyl]-2-piperazinone 1 -Chlorophenyl)-4-[ 1-(4-cyanobenzyl)-5-imidazolyimethyl]-5- r2- (ethanesul fonyl)methyl] -2 -pi perazi none 1 -Ch lorophenyl)-4-r i -(4-cyanobenzyl)- 5-i midazoiyi methyl]-5 -ethyl -2acetamido] -2-piperazinone (±)-5-(2-Butynyl)- I -chlorophenyi)-4-r 1-(4-cyanobenzyl)-5-imidazolylmethyl]-2piperazinone 1 -Chi orophenyI)-4-r [1-(4-cyanobenzyl1)- 5-imidazoi yl methyl ]-2-piperazinone 5(S)-Butyl-4-r 1-(4-cyanobenzyl-2-methyl)-5-imidazolylmethyl]- 1 -dimethyiphenyl)piperazin-2-one 1-(2-(4-Cyanophenyl)-2-propyl)-5-imidazolylmethyl]- I -(3-chlorophenyl)-5(S)-(2methyl sul fonylethyl)pi perazi n-2 -one 5(S)-n-Butyl-4-[ 1-(4-cyanobenzyl)-5-imidazolylmethyl]- 1 -(2-methylphenyl)piperazin-2one

C)

00 chlorophenyl)piperazin-2-one 4-[3-(4-Cyanobenzyl)pyridin-4-yI]- 1 -(3-chlorophenyl)-5(S)-(2-methylsulfonylethyl)piperazin-2-one 4-[5-(4-Cyanobenzyl)- 1 -imidazolylethyl]- 1 -chlorophenyl)piperazi n-2 -one or a stereoisomeric form, or a pharmaceutically acceptable acid or base addition salt form thereof, in a therapeutically effective amount.

In another aspect, the invention provides a method of treating a synucleinopathic subject by administering one or more of the following farnesyl transferase inhibitor compounds: 1- 1-(4-Nitrobenzyl)imidazolyl]methyl }-2(S)-butyl-4-( 1-naphthoyl)pipcrazine 1 1- Benzylimidazol)methyl]-2(S)-butyl-4-( 1 -naphthoyl)piperazine 1 -(2(R)-Amino-3-(3-benzylthio)propyl)-2(S)-butyl-4-(1 -naphthoyl)piperazine 1 -(2(R)-Amino-3-[3-(4-nitrobenzylthio)propyl])-2(S)-butyl-4-( I -naphthoyl)piperazine 2(S)-n-Butyl- 1 -(4-cyanobenzyl)imidazol-5-ylmethyl]-4-( I -naphthoyl)piperazine 2(S)-n-Butyl- 1-El-(4-cyanobenzyl)imidazol-5-ylmethyl]-4-(2,3 dimethylphenyl)piperazin- 2(S)-n-Butyl- 1-El-(4-chlorobenzyl)imidazol-5-ylmethyl]-4-( I-naphthoyl)piperazine 1- ([1-(4-Cyanobenzyl)- 1H-imidazol-5-yl]acetyl)}-2(S)-n-butyl-4-( 1-naphthoyl)piperazine 1 -(4-Cyanobenzyl)imidazol-5-ylmethyl]-4-(2,3-dimethylphenyl)-2(S)-(2methoxyethy l)pi perazin- 5(S)-n-Butyl-4-[ 1-(4-cyanobenzyl)-5-imidazolylmethyl]- 1 -(2-methylphenyl)piperazin-2one I -(3-Chlorophenyl)-4-[ 1-(4-cyanobenzyl)-5-imidazolylmethyl]-5-[2- (methanesulfonyl)ethyl]-2-piperazinone 1 -Chilorophenyl)-4- [1 -(4-cyanobetizyl)-5 -imidazo lyl methyl (ethanesulfonyl)ethyl] -2-piperazinone I -(3-Chlorophenyl)-4-[ 1-(4-cyanobenzyl)-5-imidazolylmethyl]-5-[2- (ethanesul fonyl)methyl] -2-piperazinone 1 -Chlorophenyl)-4- [l-(4-cyanobenzyl)-5 -imidazolyl -methyl] -2 -piperazi none or a stereoisomeric form, or a pharmaceutically acceptable acid or base addition salt form thereof, in a therapeutically effective amount.

In one embodiment, the compound may be 1 -(3-Chlorophenyl)-4-[ 1-(4-cyanobenzyl)-5im idazolyl -methyl] -2-piperazi none or a stereoisomeric form, or a pharmaceutically acceptable o acid or base addition salt form thereof.

00 In another aspect, the invention provides a method of treating a synucleinopathic subject by administering one or more of the following farnesyl transferase inhibitor compounds: 5(S)-n-Butyl-1 -d imethylphenyl)-4-(4-im idazolylmethyl)-piperazin-2 -one 5(S)-n-Butyl-4-[ I-(4-cyanobenzyl)imidazol-5-ylmethyl]- 1 -(2,3-dimethylphenyl)p'iperazin- 2-one 1-(4-Cyanobenzyl)imidazol-5-ylmethyl]- I -(2,3-dimethylphenyl)-5(S)-(2methoxyethyl)piperazin-2-one 1 -(3-Chlorophenyl)-4-[ 1-(4-cyanobenzyl)-5-imidazolylmethyl]-5-[2- (methanesulfonyl)ethyl]-2-piperazinone 1 -(3-Chlorophenyl)-4-[ 1-(4-cyanobenzyl)-5-imidazolylmethyl]-5-[2- (ethanesul fonyl)ethyl]-2-piperazinone 1 -(3-Chlorophenyl)-4-[ 1-(4-cyanobenzyl)-5-imidazolylmethyl]-5-[2- (ethanesul fonyl)methyl]-2-piperazinone 1 -(3-Chlorophenyl)-4-[ 1-(4-cyanobenzyl)-5-imidazolylmethyl]-5-[N-ethyl-2acetamido] -2-piperazinone (±)-5-(2-Butynyl)- I -(3-chlorophenyl)-4-[ I-(4-cyanobenzyl)-5-imidazolylmethyl]-2piperazinone 1 -Chi orophenyl) [1 -(4-cyanobenzyl)-5 -imidazo Iyl methyl -piperazi none 5(S)-Butyl-4-[ 1-(4-cyanobenzyl-2-methyl)-5-imidazolylmethyl]- 1 -(2,3-dimethylphenyl)piperazin-2-one I-(2-(4-Cyanophenyl)-2-propyl)-5-imidazolylmethyl]- 1 -(3-chlorophenyl)-5(S)-(2methylsulfonylethyl)piperazin-2-one 5(S)-n-Butyl-4-[ I-(4-cyanobenzyl)-5-imidazolylmethyl]- 1 -(2-methylphenyl)piperazin-2one I-(4-Cyanobenzyl)-5-imidazolylmethyl]-5(S)-(2-fluoroethyl)- 1 chlorophenyl)piperazin-2-one 4-[5-(4-Cyanobenzyl)- 1 -imidazolylethyl]- 1 -(3-chlorophenyl)piperazin-2-one.

In one embodiment, one or more compounds shown in Figure 5, Figure 2 1, and/or Figure 22 may be used.

In another aspect, the invention provides a method of treating a synucleinopathic subject by administering one or more of the following farnesyl transferase inhibitor compounds: 1I(NDilooehxpeyl4[I-4caoezliiazllehl 2pprznn -(2,Srifumeth yphenyl)4-[ -(4-cyanobenzyl)imidazolylmethyl]-2-piperazinone 1-25Dmtypey)4 1.)caoezlimiaoylehl 2p eainn o 1 -(3-Methylphenyl)-4-[ I-(4-cyanobenzyl)imidazolylmethyl]-2-piperazinone 00C-3Idpey)4[1(-ynbny)mdzlymty]2pprznn 00 1 -Cloophenyl)-4- [1 -(3hoy4-cyanobenzyl)imidazolyl methyl -2-piperazi none 1 -Trifluoromethoxyphenyl)-4- [1-(3-methoxy-4-cyanobenzyl imidazo)ylmethyl]-2piperazinone 1 -(3-chlorophenyl)-4- [1 -(4-cyanobenzyl)-imidazolylmethyl]-2piperazinone 1 -(3-Chlorophenyl)-4-[ I-(2-fluoro-4-cyanobenzyl)- I H-imidazol-5-ylmethyl]piperazin-2one I-(4-Cyanobenzyl)- I H-imidazol-5-ylmethyl]- 1 -(3-methylthiophenyl)piperazin-2-one 1-(4-Cyanobenzyl)- 1 H-imidazol-5-ylmethyl]- 1 ,5-dichlorophenyl)piperazin-2-one 1 -(3-Chlorophenyl)-4- -(4-cyanophenyl)- 1 -ethyl]- 1 H-imidazol-5-ylmethyl)piperazin-2one I -(3-Chloro-4-fluorophcnyl)-4-1I-(4-cyanobenzyl)- I H-imidazol-5-ylmethyl]-piperazin-2one 1-(4-Cyanobenzyl)- 1 H-imidazol-5-ylmethyl]- 1 -(3,5-dimethylphenyl)piperazin-2-one (S)-5-Benzyl-4-[3-(4-cyanobenzyl-lI-imidazol-5-yl)prop- l-yl) -1 -phenyl -2 -piperazi none 1 -(3-Chlorophenyl)-4-[ I-(4-nitrobenzyl)- I H-imidazol-5-ylmethyl]piperazin-2-one I-(4-Cyanobenzyl)- 1 H-imidazol-5-ylmethyl]- 1 -(3,5-difluorophenyl)piperazin-2-one I-(4-Cyanobenzyl)- 1 H-imidazol-5-ylmethyl]- I -(3,4-difluorophenyl)piperazin-2-one.

In another aspect, the invention provides a method of treating a synucleinopathic subject by administering a farnesyl transferase inhibitor compound of the formula: 1 3

(R

9 )qR

A

or a stereoisomeric form, or a pharmaceutically acceptable acid or base addition salt form thereof, in a therapeutically effective amount, wherein: __Rland R Ib are independently selected from: o a) hydrogen, 00 b) unsubstituted or substituted aryl, unsubstituted or substituted heterocycle, unsubstituted or substituted C 3 -C 10 cycloalkyl, unsubstituted or substituted C 2

-C

8 alkenyl, unsubstituted or substituted C 2

-C

8 alkynyl, R1 0 R' S(O)m, RIOC(O)NR"cL, (R 2 NCO)-, (R' 0 2

NC(O)NR'

0 CN, NO 2

R'

0

R'

0 -N(R or R"OC(O)NR or c) unsubstituted or substituted C I-C 6 alkyl wherein the substitutent on the substituted C- C) 10 C 6 alkyl is selected from unsubstituted or substituted aryl, unsubstituted or substituted heterocycle, unsubstituted or substituted C 3 -C 10 cycloalkyl, C 2

-C

8 alkenyl, C 2

-C

8 alkynyl,

R'

0

R'

0

C(O)NR'

0

(R

0 2

(R'

0 2

NC(O)NR

1 0

CN,

R'

0

R'

0

-N(R'

0 2 and R' 'OC(O)NR' 0 R 2and R 3are independently selected from: H, unsubstituted or substituted C I.

6 alkyl, unsubstituted or substituted C 2 8 alkenyl, unsubstituted or substituted C 2 8 alkynyl, unsubstituted or substituted aryl, unsubstituted or substituted heterocycle, Y

NR

6

R

7

YOR

6 0 0 wherein the substituted group is substituted with one or more of: 1) aryl or heterocycle, unsubstituted or substituted with: a) C1- 6 alkyl, b) (CH 2 )pOR 6 c) (CH 2 )pNR 6R', d) halogen, e) CN, 2) C 3 6 cycloalkyl, 6 4) SR 6 S(O)R a, S0 2 R~a -NR R' 173 6) N4

R

7

R

7 7) 0 R6

N

6

R

-0 NR 6 R7 9) 0 -OyNR 6 10) 0 11) -S0 2

-NR

6

R

7 12 1 J-SO 2

-R

6 a 13) 0 Y ~OR 6 14) 0 15) N 3 or 16) F; or R 2and R 3are attached to the same C atom and are combined to form -(CH 2 wherein one of the carbon atoms is optionally replaced by a moiety selected from: 0, and -N(COR' 0 R 4 is selected from H and unsubstituted or substituted C I-C 6 alkyl; and any two of R R 3 or Rare optionally attached to the same carbon atom;

C.)

00 a) hydrogen, b) unsubstituted or substituted aryl, unsubstituted or substituted heterocycle, unsubstituted or substituted C 3 -C 10 cycloalkyl, unsubstituted or substituted C 2

-C

8 alkenyl, unsubstituted or substituted C 2

-C

8 alkynyl, perfluoroalkyl, halo, R1 0 unsubstituted or substituted C I-C 6 alkoxy, R1 R' 0 0C(O)NR' 0

(R'

0 2

NC(O)-,

(R'

0 2

NC(O)NR'

0 CN, NO 2

R'

0

R'

0

-N(R

0 2 or R"'OC(O)NR' 0 ,and C) C 1

-C

6 alkyl, unsubstituted or substituted by aryl, cyanophenyl, heterocycle, C 3

-C

10 cycloalkyl, C 2

-C

8 alkenyl, C 2

-C

8 alkynyl, perfluoroalkyl, F, Cl, Br, R1 0 R'S(O)m-,

R'

0 C(O)NR O- (R 2 (R 0) 2

NC(O)NR'

0 CN, R R

R

1 1 0C(O)NR' 0 R 6, R 7and R 7 a are independently selected from: H, C I-C 6 alkyl, C 3 6 cycloalkyl, heterocycle, aryl, aroyl, heteroaroyl, arylsulfonyl, heteroarylsulfonyl, unsubstituted or substituted with: a) C 1 6 alkoxy, b) C I-C 2 o alkyl c) aryl or heterocycle, d) halogen, e) HO, f) -C(O)Rl1 g) -SO 2 R' or h) N(R' 0 2 or R 6 and R 7 may be joined in a ring; R7dR 7 1(a may be joined in a ring; R 6a is selected from: C I-C 6 alkyl, C 3 6 cycloalkyl, heterocycle, aryl, aroyl, heteroaroyl, arylsulfonyl, heteroarylsulfonyl, unsubstituted or substituted with: a) C 14alkoxy, b) C -C 20 alkyl c) aryl or heterocycle, d) halogen, e) HO, g) -SO 2 R1 or

C.)

00 R 8 is independently selected from: a) hydrogen, b) unsubstituted or substituted aryl, unsubstituted or substituted heterocycle, unsubstituted or substituted C 3 -CIO cycloalkyl, unsubstituted or substituted C 2

-C

8 alkenyl, unsubstituted or substituted C 2

-C

8 alkynyl, perfluoroalkyl, halo, R' 0 unsubstituted or INDsubstituted CI-C 6 alkoxy, R R' 0

C(O)NR'

0 (R 0 2

NC(OI)H,

10 1 01 (R 2 NC(O)NR CN, NO 2

R'

0 -N(R 0)2, or R 1

'OC(O)NR'

0 and C) CI-C 6 alkyl unsubstituted or substituted by aryl, cyanophenyl, heterocycle, C 3

-C

10 cycloalkyl, C 2 -C8 alkenyl, C 2

-C

8 alkynyl, perfluoroalkyl, halo, R' 0

R'

0 C(0)NR' 0

(R'

0

(R'

0 2

NC(O)NR'

0 CN, R' 0

R'

0

N(R'

0 2 or R"C(O)NR' 0

R

9 is selected from: a) hydrogen, b) unsubstituted or substituted aryl, unsubstituted or substituted heterocycle, unsubstituted or substituted C 3 -C 10 cycloalkyl, unsubstituted or substituted C 2

-C

8 alkenyl, unsubstituted or substituted C 2

-C

8 alkynyl, perfluoroalkyl, halo, R1 0 R" S(O)m-,

R'

0

C(O)NR'

0

(R'

0 2

(R'

0 2

NC(O)NR'

0 CN, NO 2

R'

0

RI

0 0C(O)-, -N('02,or R"OC(O)NR' 0 and C) CI-C 6 alkyl unsubstituted or substituted by aryl, heterocycle, C 3 -Clocycloalkyl, perfluoroalkyl, halo, R' 0 0, R" R' 0

C(O)NR

1 0

(R'

0 2

(R'

0 2

NC(O)NR'

0 CN, R' 0

R'

0

-N(R'

0 2 or R"'OC(O)NR' 0 R1 0 isindependently selected from hydrogen, unsubstituted or substituted C 1

-C

6 alkyl, perfluoroalkyl, unsubstituted or substituted aralkyl, and unsubstituted or substituted aryl; R" is independently selected from unsubstituted or substituted CI-C 6 alkyl and unsubstituted or substituted aryl; A' and A 2 are independently selected from: a bond,

-C(O)NR'

0

-NR

0 0, -N(R' 0

-S(O)

2

-N(R

0

)S(O)

2 or S(O)"m; A 3 is selected from -C(R la) 2 0, 4-(R) 0 afld S(O)m; G' or G 2is selected from H 2 or 0, provided that if G1 isO0 then G 2 is H 2 and if G 2is 0,

ID

Sthen G' is H 2 V is selected from: O a) heterocycle, and 00 b) aryl, W is a heterocycle; Y is heteroaryl; Z is a unsubstituted or substituted group selected from aryl, heteroaryl, arylmethyl, heteroarylmethyl, arylsulfonyl, heteroarylsulfonyl, wherein the substituted group is \0 substituted with one or more of the following: 0 10 1. CI-C 6 alkyl, unsubstituted or substituted with: a) C.- 6 alkoxy, b) NR 6

R

7 c) C3- 6 cycloalkyl, d) aryl or heterocycle, e) HO, f) -S(O)mRa, or g) -C(O)NR 6

R

7 2. unsubstituted or substituted aryl or unsubstituted or substituted heterocycle, 3. halogen, 4. OR,

NR

6

R

7 6. CN, 7. NO 2 8. CF 3 9. -S(O)mR 6a

-C(O)NR

6

R

7 11.-OCF 3 12. unsubstituted or substituted Ci-6 alkoxy, 13. C 2

-C

8 alkenyl, 14. C 2 -C8 alkynyl, or

C

3 -Cio cycloalkyl; m is 0, 1 or 2; n is0, 1,2, 3 or 4; pis0, 1,2, 3 or4;

ID

q is 0,1 or 2; r is 0 to Ss is 0 or 1; 00 tis 0 to u is 4 or 5; and x is 0, 1, 2, 3or 4.

In another aspect, the invention provides a method of treating a synucleinopathic subject S by administering a farnesyl transferase inhibitor compound of the formula:

(N

R5 t

R

3

A

3

(R

9 )q thereof, in a therapeutically effective amount, wherein: Ra and Rib are independently selected from: a) hydrogen, b) unsubstituted or substituted aryl, unsubstituted or substituted heterocycle, unsubstituted or substituted C 3 -Ci 0 cycloalkyl, R'oO-, 2 or, C 2

-C

8 alkenyl, or c) unsubstituted or substituted CI-C 6 alkyl wherein the sub stitutent on the substituted Ci-

C

6 alkyl is selected from unsubstituted or substiutted aryl, unsubstituted or substituted heterocycle, unsubstituted or substituted C 3 -Cio cycloalkyl, C 2

-C

8 alkenyl, or N(RIn)2

R

2 and R 3 are independently selected from: H, unsubstituted or substituted Ci-6

NR

6

R

7 O wherein the substituted group is substituted with one or more of: 1) aryl or heterocycle, unsubstituted or substituted with: 178 a) C I-C 6 alkyl, b) (CH,),OR, O~ 67 o) c) (CH 2 )pNRR 00 d) halogen, e) CN; 2. C 3 6 cycloalkyI; 3. OR;6 4. SR 6 S(O)R a, S0 2 R~a IND 5) -NR 6 R 7 6) 0 -Ny NR 7 R 7 a 7) 0 0 y NR 6

R

7 8) 0 -0 y NR 6 9) 0 y

~NR

6 R 7 0 11) -S0 2

-NR

6

R

7 12)

-SO

2

-R

6 a 00

R

13) 0

OR

6 14) 0

N

3 or 16) F;or R 2and R 3 are attached to the same C atom and are combined to form -(CH 2 wherein one of the carbon atoms is optionally replaced by a moiety selected from: 0, S(O)' 1 and R 4 is selected from H and unsubstituted or substituted C I-C 6 alkyl; and any two of R 2 R 3 or R4are optionally attached to the same carbon atom;

R

5 is independently selected from: a) hydrogen, b) unsubstituted or substituted aryl, unsubstituted or substituted heterocycle, unsubstituted or substituted C 3 -CIO cycloalkyl, unsubstituted or substituted C 2

-C

8 alkenyl, unsubstituted or substituted C 2

-C

8 alkynyl, perfluoroalkyl, halo, R' 0 unsubstituted or substituted C I-C 6 alkoxy, R1 R' 0

C(O)NR'

0

(R'

0 2 NC(0H-, (R' 0 2 NC(O)NR'-, CN, NO 2

R'

0

R'

0

-N(R

0 2 or R'"OC(O)NR' 0 and C) C,-C 6 alkyl unsubstituted or substituted by aryl, cyanophenyl, heterocycle, C 3

-C

10 cycloalkyl, C 2

-C

8 alkenyl, C 2

-C

8 alkynyl, perfluoroalkyl, F, Cl, Br, R 10 R"S(O)m,-

R'

0

C(O)NR'

0

(R'

0 2

(R'

0 2 NC(O)NR'-, CN, R' 0

R'

0 NR),or R"OC(O)NR' 0 R 6, R 7and R 7 aare independently selected from: H, CI-C 6 alkyl, C 3 6 cycloalkyl, heterocycle, aryl, aroyl, heteroaroyl, arylsulfonyl, heteroarylsulfonyl, unsubstituted or substituted with: a) C 1 6 alkoxy, b) C I-C 2 0 alkyl

I

c) aryl or heterocycle, d) halogen, o e) HO, 00 g) -SO 2 R 1 or h) N(R' 0 2 or R6 adR7 myb ondi ig R 7and R 7amay be joined in aring; IND R a is selected from: CI-C 6 alkyl, C 3 6 cycloalkyl, heterocycle, aryl, aroyl, heteroaroyl, C) 10 arylsulfonyl, heteroarylsulfonyl, unsubstituted or substituted with: a) C1 6 alkoxy, b) C I-C 2 0 alkyl c) aryl or heterocycle, d) halogen, e) HO, f) -C(O)R 1 g) -S0 2

R

1 1 or h) N(R' 0 2 or R 8 isindependently selected from: a) hydrogen, b) unsubstituted or substituted aryl, unsubstituted or substituted heterocycle, unsubstituted or substituted C 3

-CI

0 cycloalkyl, unsubstituted or substituted C 2

-C

8 alkenyl, unsubstituted or substituted C 2

-C

8 alkynyl, perfluoroalkyl, halo, R' 0 unsubstituted or substituted CI-C 6 alkoxy, R" 1S(O)m R' 0

C(O)NR'

0

(R'

0 2

(R'

0 2

NC(O)NR'

0 CN, N0 2

R'

0

C(O)-

,R'

0

-N(R

0 2 or R"OC(O)NR' 0 and C) CI-C 6 alkyl unsubstituted or substituted by aryl, cyanophenyl, heterocycle, C 3

-C

10 cycloalkyl, C 2

-C

8 alkenyl, C 2

-C

8 alkynyl, perfluoroalkyl, F, Cl, Br, R' 0 R" S(O)m'-

R'

0

C(O)NR'

0

(R'

0 2

(R'

0 2

NC(O)NR'

0 CN, R' 0

R

1 0

R'"OC(O)NR'

0

R

9 is selected from: a) hydrogen, b) unsubstituted or substituted aryl, unsubstituted or substituted heterocycle, unsubstituted or substituted C 3 -C 10 cycloalkyl, unsubstituted or substituted C 2

-C

8 alkenyl, unsubstituted or substituted C 2

-C

8 alkynyl, perfluoroalkyl, halo, R' 0 R"

R'

0

C(O)NR'

0

(R

1 2

(R'

0 2

NC(O)NR'

0 R CN, NO 2

R'

0

N

3

-N(R

0 2 or R' OC(O)NR and

C.)

00 perfluoroalkyl, halo, R' 0 R' R' 0

C(O)NR'

0

(R'

0 2

NC(O)-,

(R'

0 2

NC(O)NR'

0 CN, R' 0

R'

0

-N(R

0 2 or R"OC(O)NR' 0 R1 0 is independently selected from hydrogen, unsubstituted or substituted C 1

-C

6 alkyl, perfluoroalkyl, unsubstituted or substituted aralkyl, and unsubstituted or substituted aryl; R" is independently selected from unsubstituted or substituted CI-C 6 alkyl and unsubstituted IND or substituted aryl; 1 2 A and A are independently selected from: a bond, C(O)NR -NR 0, -N(R -S(O) 2 N(R -N(R 0

)S(O)

2 or S(O)m A 3 is selected from -C(Rla 2 0, -N(R and S(O),m; W is a heterocycle selected from imidazolyl, pyridyl, thiazolyl, indolyl, quinolinyl, isoquinolinyl and thienyl; Y is heteroaryl; Z is a unsubstituted or substituted group selected from aryl, heteroaryl, arylmethyl, heteroarylmethyl, arylsulfonyl, heteroarylsulfonyl, wherein the substituted group is substituted with one or more of the following: I1. C I-C 6 alkyl, unsubstituted or substituted with: a) C 1 6 alkoxy, b) NR 6

R',

C) C 3 6 cycloalkyl, d) aryl or heterocycle, e) HO, 6, f) -S(O)mR or g) -C(O)NRR', 2. unsubstituted or substituted aryl or unsubstituted or substituted heterocycle, 3. halogen, 4. OR 6 5. NR 6

R',

6. CN, 7. NO 2 8. CF 3

R

ID

-C(O)NR

6

R

7 11. C 3

-C

6 cycloalkyl, O 12. -OCF 3 or 00 13. unsubstituted or substituted C .6 alkoxy; m is 0, 1 or 2; n is 0, 1,2, 3 or 4; Sp is 0, 1, 2, 3or 4; S q is 0, 1 or 2; NO r is0 to

O

t is 0 to u is 4 or 5; and x is 0, 1,2, 3or 4.

In another aspect, the invention provides a method of treating a synucleinopathic subject by administering a farnesyl transferase inhibitor compound of the formula:

(R

5 )t Y (R 9 )q

N

3 R\ R 3 0 (CRa

II

(CR'b 2 p N N- Z

R

4 or a stereoisomeric form, or a pharmaceutically acceptable acid or base addition salt form thereof, in a therapeutically effective amount, wherein: R l a and Rlb are independently selected from: a) hydrogen, b) unsubstituted or substituted aryl, unsubstituted or substituted heterocycle, unsubstituted or substituted C 3 -Clo cycloalkyl, unsubstituted or substituted C 2

-C

8 alkenyl, R' 0 or -N(R 0)2, or c) unsubstituted or substituted C I-C 6 alkyl wherein the substitutent on the substituted C I-C 6 alkyl is selected from unsubstituted or substituted aryl, unsubstituted or substituted heterocycle, o unsubstituted or substituted C 3 -CIO cycloalkyl, C 2

-C

8 alkenyl, R' 0 or -N(R 0)2; 00 R 2is H, unsubstituted or substituted C 1 6 alkyl, or Y NR 6 R 7 0 IND wherein the substituted group is substituted with one or more of: C) 1) aryl, 2) heterocycle, 3) OR 6 6a 6a 4) SR S0 2 R ,or Y NR 6 R 7 0 R 3 and R 4 are independently selected from H and unsubstituted or substituted C I-C 6 alkyl; and any two of R 2 R 3 or R4are optionally attached to the same carbon atom;

R

5 is independently selected from: a) hydrogen, b) unsubstituted or substituted aryl, unsubstituted or substituted heterocycle, unsubstituted or substituted C 3 -C 10 cycloalkyl, unsubstituted or substituted C 2

-C

8 alkenyl, unsubstituted or substituted C 2 -C8 alkynyl, perfluoroalkyl, halo, R1 0 unsubstituted or substituted C I-C 6 alkoxy, R" R 1 0

C(O)NR'

0

(R'

0 2

(R'

0 2

NC(O)NR'

0 CN, NO 2

R'

0

R'

0

-N(R

0 2 or R"OC(O)NR' 0 and C) CI-C 6 alkyl unsubstituted. or substituted by aryl, cyanophenyl, heterocycle, C 3

-C

10 cycloalkyl, perfluoroalkyl, F, Cl, Br, R' 0

R'

0

C(O)NR'

0

(R'

0 2

NO)-,

(R'

0 2

NC(O)NR'

0 CN, R' 0

R'

0

-N(R

0 2 or R 1

IOC(O)NR

1 0 R 6 and R 7 are independently selected from: H, C I-C 6 alkyl, C 3 6 cycloalkyl, heterocycle, aryl, unsubstituted or substituted with: a) C 16 alkoxy, b) C I-C 2 oalkyl c) aryl or heterocycle, d) halogen, or o e) HO; 00 ~R 6 and R 7 may be joined in a ring; R 6 ais selected from: C I-C 6 alkyl, C 3 6 cycloalkyl, heterocycle, aryl, aroyl, heteroaroyl, arylsulfonyl, heteroarylsulfonyl, unsubstituted or substituted with: a) C 1 6 alkoxy, b) C I-C 2 0 alkyl c) aryl or heterocycle, IND d) halogen, or e) HO; R 8 is independently selected from: a) hydrogen, b) unsubstituted or substituted aryl, unsubstituted or substituted heterocycle, unsubstituted or substituted C 3 -CIO cycloalkyl, unsubstituted or substituted C 2

-C

8 alkenyl, unsubstituted or substituted C 2

-C

8 alkynyl, perfluoroalkyl, halo, R' 0 unsubstituted or substituted C 1

-C

6 alkoxy, R' R' 0

C(O)NR'

0

(R'

0 2

(R'

0 2

NC(O)NR'

0 CN, NO 2

R'

0

R'

0

-N(R'

0 2 or R"OC(O)NR' 0 and C) C I -C 6 alkyl unsubstituted or substituted by aryl, cyanophenyl, heterocycle, C 3 -C 1 0 cycloalkyl, perfluoroalkyl, halo, R' 0

R

11

R'

0

C(O)NR'

0

(R'

0 2 NC(01-,

(R'

0 2

NC(O)NR'

0 CN, R' 0

R'

0

-N(R'

0 2 or R' 0 0C(O)NR' 0

R

9 isselected from: a) hydrogen, b) unsubstituted or substituted aryl, unsubstituted or substituted heterocycle, unsubstituted or substituted C 3 -CIO cycloalkyl, unsubstituted or substituted C 2

-C

8 alkenyl, unsubstituted or substituted C 2

-C

8 alkynyl, perfluoroalkyl, halo, R' 0 R' R' 0

C(O)NR'

0

(R'

0 2

(R'

0 2

NC(O)NR'

0 CN, NO 2

R'

0

R'

0

-N(R

0 2 or

R"OC(O)NR'

0 and C) CI-C 6 alkyl unsubstituted or substituted by aryl, heterocycle, C 3 -ClOcycloalkyl, perfluoroalkyl, halo, R' 0 R' R' 0

C(O)NR'

0

(R'N)NCO),

(R'

0 2

NC(O)NR'

0 CN, R' 0

R'

0

-N(R

0 2 or R"OC(O)NR 1 0 R 1 0 is independently selected from hydrogen, unsubstituted or substituted C I-C 6 alkyl, perfluoroalkyl, unsubstituted or substituted aralkyl, and unsubstituted or substituted aryl; R"1 is independently selected from unsubstituted or substituted C I -C 6 alkyl and unsubstituted or substituted aryl; A 3 is selected from -C(R a 2 0, -N(R' 0 and S(O)m,; Y is heteroaryl; Z is a unsubstituted or substituted group selected from aryl, heteroaryl, arylmethyl, 00 heteroarylmethyl, wherein the substituted group is substituted with one or more of the following: 1. cI 6 alkyl, unsubstituted or substituted with: a) C 16 alkoxy, b) NR R C) C 3 6 cycloalkyl, d) aryl or heterocycle, e) HO, -S(O)mR 6 a, or g) -C(O)NR 6 R 7 2. unsubstituted or substituted aryl or unsubstituted or substituted heterocycle, 3. halogen, 4. OR 6 5. NR 6 R 7 6.

ID CN, 7. NO 2 8. CF 3 9. -S(O)mR a, 10. -C(O)NR R, I11. C 3 -Cccoly,1.-C 3 or 13. unsubstituted or substituted C 1 6 alkoxy; mis 0, 1 or 2; nisO, 1,2, 3or 4; pisO, 1,2, 3or 4; qisO, I or 2; risOto 5; tisOto 5;and u is 4 or In another aspect, the invention provides a method of treating a synucleinopathic subject by administering a farnesyl transferase inhibitor compound of the list comprising of: (3chlorophenyl)-4- [1 -pyridyloxy)-4-cyanobenzyl)-5 imidazolyl methyl] -2-p iperazi none; and I -(2-(n-Butyloxy)phenyl)-4-[ 1-(3-((6-methyl-2-pyridyl)oxy)-4-cyanobenzyl)-2-methyl-5imidazolylmethyl] -2-piperazinone; or a stereoisomeric form, or a pharmaceutically acceptable acid or base addition salt form thereof, in a therapeutically effective amount.

In another aspect, the invention provides a method of treating a synucleinopathic by administering one or more of the following a farnesyl transferase inhibitor compounds: I-(3chlorophenyl)-4-[1 -((2-chlorophenyl)oxy)-4-cyanobenzyl)-5-imidazolylmethyl]-2piperazinone; 1 -(3-chlorophenyl)-4-[ 1-(3-((3-chlorophenyl)oxy)-4-cyanobenzyl)-5imidazolylmethyl]-2-piperazinone; 1 -chlorophenyl)-4- -((4-chlorophenyl)oxy)-4cyanobenzyl)-5-imidazolylmethyl]-2-piperazinone; 1 -(3-chlorophenyl)-4- [1 b iphenyl yl)oxy)-4-cyano benzyl)-5 imidazo lyl methyl] -2-pi perazi none; 1 -chlorophenyl)-4-[ 1- (3 -(2-hydroxy- 1 -ethoxy)phenyl)oxy)-4-cyanobenzyl)-5-imidazolylmethyl] -2-piperazinone; 1 -chlorophenyl)-4- -((4-(benzyloxy)phenyl)oxy)-4-cyanobenzyl)-5 -imidazolylmethyl] 2-piperazinone; and 1 -(2-(n-Butyloxy)phenyl)-4- -(2-hydroxy-lI-ethoxy)phenyl)oxy)-4cyanobenzyl)-2-methyl-5-imidazolylmethyl]-2-piperazinone, or a stereoisomeric form, or a pharmaceutically acceptable acid or base addition salt form thereof, in a therapeutically effective amount.

In one embodiment, the compound may be 1-(3-chlorophenyl)-4-[1-(3-((2ch lorophenyl)oxy)-4-cyanobenzyl)-5 -imidazolylmethyl] -2-piperazi none. In another 186 embodiment, the compound may be 1 -chlorophenyl)-4- -chlorophenyl)oxy)-4cyanobenzyl)-5-imidazolylmethyl] -2-piperazinone. In another embodiment, the compound may o be 1 -chlorophenyl)-4- -((4-chlorophenyl)oxy)-4-cyanobenzyl)-5 -imidazolylmethyl] -2- 00 piperazinone. In another embodiment, the compound may be 1-(3 -chilorophenyl)-4- bi phenylIylI)oxy)-4-cyanobenzyl)-5 -i midazolylmethy1] -2-piperazi none. In another embodiment, the compound may be 1 -chlorophenyl)-4- [1 -(2-hydroxy- 1 -ethoxy)phenyl)oxy)-4- -imidazolylmethyl] -2-piperazinone. In another embodiment, the compound may be 1 -chlorophenyl)-4- -((4-(benzyloxy)phenyl)oxy)-4-cyanobenzyl)-5 IND imidazolylmethyl]-2-piperazinone. In another embodiment, the compound may be 1 C) 10 Butyloxy)phenyl)-4-[ 1-(3-((3-(2-hydroxy-l1-ethoxy)phenyl)oxy)-4-cyanobenzyl)-2-methyl-5m idazolIyl methyl -piperazi none.

In another aspect, the invention provides a method of treating a synucleinopathic subject by administering one or more of the following farnesyl transferase inhibitor compounds: 2(S)- Butyl-l1-(2,3-diaminoprop- 1-yl)- 1-(1 -naphthoyl)piperazine; I -(3-Amino-2-(2naphthylmethylamino)prop- 1-yl)-2(S)-butyl-4-( 1-naphthoyl)piperazine; 2(S)-Butyl- 1-f{5-ri }methyl-4-( 1-naphthoyl)piperazine; 1 1- Benzylimidazol)methyl]-2(S)-butyl-4-( I-naphthoyl)piperazine; 1- 1-(4nitrobenzyl)] imidazolylmethyl)}-2(S)-butyl-4-( I-naphthoyl)piperazine; 1 Acetamidomethylthio-2(R)-aminoprop-1I-yl)-2(S)-butyl-4-( 1-naphthoyl)piperazine; 2(S)-Butyl- 1 1-imidazolyl)ethyl] sulfonyl-4-( 1-naphthoyl)piperazine; 2(R)-Butyl-l1-imidazolyl-4methyl-4-( 1 -naphthoyl)piperazine; 2(S)-Butyl-4-( I -naphthoyl)- 1 -(3-pyridylmethyl)piperazine; 1 -2(S)-butyl-(2(R)-(4-nitrobenzyl)amino-3-hydroxypropyl)-4-(l1-naphthoyl)piperazine; 1 Amino-3 -hydroxyheptadecyl)-2(S)-butyl-4-( 1-naphthoyl)-piperazine; 2(S)-Benzyl -1imidazolyl-4-methyl-4-( I-naphthoyl)piperazine; 1 -(2(R)-Amino-3-(3-benzylthio)propyl)-2(S)butyl-4-( I-naphthoyl)piperazine; I -(2(R)-Amino-3-[3-(4-nitrobenzylthio)propyl])-2(S)-butyl-4- (1 -naphthoyl)piperazine; 2(S)-Butyl-l1-[(4-imidazolyl)ethyl]-4-(1 -naphthoyl)piperazine; 2(S)- Butyl-lI-[(4-imidazolyl)methyl]-4-( I-naphthoyl)piperazine; 2(S)-Butyl- I [(1-naphth-2ylmethyl)- IH-imidazol-5-yl)acetyl]-4-( I-naphthoyl)piperazine; 2(S)-Butyl- I-naphth-2ylmethyl)- 1H-imidazol-5-yI)ethyl]-4-( 1-naphthoyl)piperazine; I -(2(R)-Amino-3hydroypropyl)-2(S)-butyl-4-(1 -naphthoyl)piperazine; I -(2(R)-Amino-4-hydroxybutyl)-2(S)butyl-4-( 1-naphthoyl)piperazine; I -(2-Amino-3-(2-benzyloxyphenyl)propyl)-2(S)-butyl-4-( 1naphthoyl)piperazine; 1 -(2-Amino-3-(2-hydroxyphenyl)propyl)-2(S)-butyl-4-( 1naphthoyl)piperazine; 1 -[3-(4-imidazolyl)propyl]-2(S)-butyl-4-( 1-naphthoyl)-piperazine; 2(S)n-Butyl-4-(2,3 -dimethylphenyl)- I -(4-imidazolylmethyl)-piperazin-5 -one; 2(S)-n-Butyl-l1-[1 -ylmethyl] -dimethylphenyl)piperazin-5 -one; 1- [1 Cyanobenzyl)imidazol-5-ylmethyi]-4-(2,3-dimethylphenyl)-2(S)-(2-methoxyethyl)piperazin-5o one; 2(S)-n-Butyl-4-( 1-naphthoyl)- 1-11-(1 002(S)-n-Butyl-4-( 1-naphthoyl)- 1-El-(2-naphthylmethyl)imidazol-5-ylmethyl]-piperazine; 2(S)-n- Butyl-1-ri -(4-cyanobenzyl)imidazol-5-ylmethyl]-4-( I-naphthoyl)piperazine; 2(S)-n-Butyl-l1-[1- (4-methoxybenzyl)imidazol-5-ylmethyl]-4-( 1 -naphthoyl)piperazine; 2(S)-n-Butyl- 1 1 methyl-2-butenyl)imidazol-5-ylmethyl-4-( I -naphthoyl)piperazine; 2(S)-n-Butyl- I1 -1 -4 fluorobenzyl)imidazol-5-ylmethyl]-4-( 1 -naphthoyl)piperazine; 2(S)-n-Butyi- 1-ri chlorobenzyl)imidazol-5-ylmethyl]-4-( 1-naphthoyl)piperazine; 1-[i -(4Bromobenzyl)imidazol- C) 10 5-ylmethyl]-2(S)-n-butyl-4-( 1-naphthoyl)piperazine; 2(S)-n-Butyl-4-( 1-naphthoyl)- 1-[I 2(S)-n-Butyl- -(4 methylbenzyl)imidazol-5-ylmethyl]-4-( 1-naphthoyl)-piperazine; 2(S)-n-Butyl- 1-[1 -ylmethyl] 1-naphthoyl)-piperazine; 1-El Phenylbenzyl)imidazol-5-ylmethyl]-2(S)-n-butyl-4-( 1-naphthoyl)-piperazine; 2(S)-n-Butyl-4- (1 -naphthoyl)- I1-[ I -(2-phenylethyl)imidazol-5-ylmethyl]-piperazine; 2(S)-n-Butyl-4-( 1naphthoyl)- 1-[i -(4-trifluoromethoxy)imidazol-5-ylmethyl]piperazine; 1-1 [1 -(4-cyanobenzyl)- I H-imidazol-5-yl]acetyl]-2(S)-n-butyl-4-( 1 -naphthoyl)piperazine; 1 -Chilorophenyl)-4-r[ 1- -imidazolylmethyl -[2-(methanesul fonyl)ethyl ]-2-pi perazi none; Chlorophenyl)-4-[ 1-(4-cyanobenzyl)-5-imidazolylmethyl]-5-E2-(ethanesulfonyl)ethyl]-2piperazinone; I-(3-Chlorophenyl)-4-E 1-(4-cyanobenzyl)-5-imidazolylmethyl]-5-[2- (ethanesul fonyl)methy1] -2-pi perazi none; 1-(3-Chlorophenyl)-4-E 1-(4-cyanobenzyl)-5imidazolylmethyl]-5-[N-ethyl-2-acetamido]-2-piperazinone; (±)-5-(2-Butynyl)- 1-(3chlorophenyl)-4-E 1-(4-cyanobenzyl)-5-imidazolylmethyl]-2-piperazinone; 1 -Chlorophenyl)- 4- [1 -(4-cyanobenzyl)- 5-imidazo lyl methyl] -2-piperazi none; 5(S)-Butyl-4-E 1-(4-cyanobenzyl-2methyl)-5-imidazolylmethyl]-l1-(2,3-dimethylphenyl)-piperazin-2-one; 4-El 1-(3-chlorophenyl)-5(S)-(2methylsulfonylethyl)piperazin-2-one; 5(S)-n-Butyl-4-[ 1-(4-cyanobenzyl)-5imidazolylmethyl]-(2-methylphenyl)piperazin-2-one; 4-Il-(4Cyanobenzyl)-5imidazolylmethyl]-5(S)-(2-fluoroethyl)- 1-(3-chlorophenyl)piperazin-2-one; Cyanobenzyl)pyridin-4-yl]- I-(3-chlorophenyl)-5(S)-(2-methylsulfonylethyi)-piperazin-2-one; 4-E5-(4-Cyanobenzyl)-l1-imidazolylethyl]- 1-(3-chlorophenyl)piperazin-2-one; 4- 2-H-pyridin- 1-yl)benzyl-3-H-imidazol-4-ylmethyl]benzonitrile; 4- 3 -4-3 -Methyl-2-oxo-2-Hpyridin- 1-yI)benzyl]-3-H-imidazol-4-ylmethyl]benzonitrile; 4-({3-E4-(-2-Oxo-piperidin- 1yl)benzyl]-3-H-imidazol-4-ylmethyl]benzonitrile; 4-1{3-[3-Methyl-4-(2-oxopiperidin- l-yI)benzyl]-3-H-imidizol-4-ylmethyl }-benzonitrile; {3-[4-(2-Oxo-pyrrolidin- 1-yl)-benzyl]-3Himidizol-4-ylmethyl)}-benzonitrile; 4-1 3-[4-(3-Methyl-2-oxo-2-H-pyrazin- 1-yl)-benzyl-3-Ho imidizol-4-ylmethyl)}-benzonitrile; 4- {3-[2-Methoxy-4-(2-oxo-2-H-pyridin-1I-yl)-benzyl]-3-H- 00 imidizol-4-ylmethyl }-benzonitrile; 4- 1-[4-(5-Chloro-2-oxo-2H-pyridin- 1-yI)-benzyl]- 1Hpyrrol-2-ylmethyl }-benzonitrile; I-(2-Oxo-2H-[1I,2']bipyridinyl-5 '-ylmethyl)- 1H-pyrrol-2ylmethyl]-benzonitrile; 1-(5-Chloro-2-oxo-2H-[ 1,2']bipyridinyl-5 '-ylmethyl)- 1H-pyrrol-2ylmethyl]-benzonitrile; 4-[3-(2-Oxo-l1-phenyl- 1,2-dihydropyridin-4-ylmethyl)-3 H-imidazol-4ylmethyl]benzonitrile; 4- 1-(3-Chloro-phenyl)-2-oxo- 1,2-dihydropyridin-4-ylmethyl]-3 Himidazol-4-ylmethyl }benzonitrile; 1 9,20-Dihydro- 19-oxo-5H,1I7H- 18,21 -ethano-6, 10:12,16- C) 10 dimetheno-22H-imidazo[3,4-h] [1,8,11,1 4]oxatriazacycloeicosine-9-carbonitrile; 1 9-Chloro- 22,23-dihydro-22-oxo-5H-2 1,24-ethano-6,1I0-metheno-25H-dibenzo[b,e] imidazo[4,3- 1] [1,4,7,10,1 3]dioxatriazacyclononadecine-9-carbonitrile; 22,23-Dihydro-22-oxo-5H-2 1,24ethano-6, 10-metheno-25H-dibenzo[b,e]imidazo[4,3-1] [1,4,7,10,1 3]dioxatriazacyclononadecine- 9-carbonitrile; 20-Chloro-23,24-dihydro-23-oxo-5 H-22',25-ethano-6, 10:12,1 6-dimetheno- 1 2H,26H-benzo[bjimidazo[4,3-i] [1,17,4,7,1 0]dioxatriazacyclohemicosine-9-carbonitrile; 20-Chloro-23 ,24-dihydro-27-[2-(methylsulfonyl)ethyl]-23-oxo-5H-22,25-ethano-6, 10:12,16dimetheno-1I2H,26H-benzo[b]imidazo[4,3-i] [1,17,4,7,1 0]dioxatriazacyclohemicosine-9carbonitrile; 1 9,20-Dihydro- I 9-oxo-5H- 18,21 -ethano- 1 2,1 4-etheno-6, I 0-metheno-22Hbenzo[d] imidazo[4,3-k] [1,6,9,1 2]oxatriazacyclooctadecine-9-carbonitrile; (+)-1I9,20-Dihydro- 1 9-oxo-5H- 18,21 -ethano- 12,1 4-etheno-6,1I0-metheno-22H-benzo[d]imidazo[4,3 k] [1,6,9,1 2]oxatriazacyclooctadecine-9-carbonitrile; (-)-1I9,20-Dihydro-1I9-oxo-5H- 18,21 ethano- 12,1 4-etheno-6, 10-metheno-22H-benzo[d]imidazo[4,3k] 1,6,9,1 2]oxatriazacyclooctadecine-9-carbonitrile; 5H, 1 7H,20H- 18,21 -Ethano-6, 10:12,16dimetheno-22H-imidazo[3 [1,8,11,1 4]oxatriazacycloeicosin-20-one; 19,20-Dihydro-3methyl-i 9-oxo-5H- 18,21 -ethano- 12,1 4-etheno-6,1I0-metheno-22H-benzo[d] imidazo[4,3k] [1,6,9,1 2]oxatriazacyclooctadecine-9-carbonitrile; or (-)-1I9,20-Dihydro-3-methyl- 19- 18,21 -ethano- 12,1 4-etheno-6, 10-metheno-22H-benzo[d] imidazo[4,3 k] 1,6,9,1 2]oxatriazacyclooctadecine-9-carbonitrile; (Enantiomner A) or 1 9,20-Dihydro- 3-methyl- I 9-oxo-5H- 18,2 1 -ethano- 1 2,1 4-etheno-6, I 0-metheno-22H-benzo[d]imidazo[4,3k] [1,6,9,1 2]oxatriazacyclooctadecine-9-carbonitrile; (Enantiomer B) 19,20-Dihydro- 19,22- 18,21 -ethano- 12,1 4-etheno-6, 10-metheno-22H-benzo[d] imidazo[4,3k] 1,6,9,1 2]oxatriazacyclooctadecine-9-carbonitrile; 325 18,1 9-dihydro- I 9-oxo-5H, 1 7H-6, 12, 1 6-dimetheno- 1 H-imidazo[4,3-c] 1, 1 1,4]dioxaazacyclononadecine-9-carbonitrile; 17,18dihydro- 1 8-oxo-5H-6, 10:12,1 6-dimetheno- 1 2H,20H-imidazo[4,3c] [1,l1,4]dioxaazacyclooctadecine-9-carbonitrile; 17,18,1 9,20-tetrahydro- 19-phenyl-5H- 6,10:12,1 6-dimetheno-2 1 H-imidazo[3 [1,8,11I ]oxadiazacyclononadecine-9-carbonitrile; o 21 ,22-dihydro-5H-6, 10:12,1 6-dimetheno-23H-benzo[g] imidazo[4,3- 00 1] 1,8,11 ]oxadiazacyclononadecine-9-carbonitrile; 22,23-dihydro-23-oxo-5H,2 1 H-6, 10:12,16dimetheno-24H-benzo g] imidazo[4,3-m] [1,8,1 2]oxadiazaeicosine-9-carbonitrile; 22,23dihydro-5H,21IH-6, 10:12,1 6-dimetheno-24H-benzo[g]imidazo[4,3-m] [1,8,1 1]oxadiazaeicosine- 9-carbonitrile; 1 -trifluoromethoxyphenyl)-4- [1-(4-cyano-3 methyl] -2-piperazi none; or a pharmnaceutically acceptable salt, stereoisomer or optical isomer IND thereof. Specific examples of a farnesyl-protein transferase inhibitor are 1-(3-Chlorophenyl)-4- [1 -(4-cyanobenzyl)- 5-imni dazo lyl methyl] -2-piperazi none; 1 -Chilorophenyl)-4- [1 cyanobenzyl)- 5-i midazo lyl methyl] -5 -[2-(ethanesulIfonyl)methyl] -2-pi perazi none; Chloro-2-oxo-2H-[ 1,2']bipyridinyl-5 '-ylmethyl)- 1H-pyrrol-2-ylmethyl]-benzonitrile; and 1 (1 -(4-cyanobenzyl)-5-imidazolylmethyl)-N-(4-cyanobenzyl)amino]-4-(phenoxy)benzene; 1 9,20-Dihydro-1I9-oxo-5 H- 18,21 -ethano- 12, 1 4-etheno-6, 10-metheno-22H- 1 5 benzo[d] imidazo[4,3-k] [1,6,9,1 2]oxatriaza-cyclooctadecine-9-carbonitrile; 1 trifluoromethoxyphenyl)-4- [1-(4-cyano-3 -methoxybenzyl)-5 -imidazolyl methyl]-2piperazinone; 3-(biphenyl-4-ylmethoxy)-4-imidazol- 1-ylmethyl-benzonitrile; 3-(biphenyl-4-yl- 2-ethoxy)-4-imidazol- 1-ylmethylbenzonitrile; 3-(biphenyl-3 -ylmethoxy)-4-imidazol- 1ylmethyl-benzonitrile; 2-(biphenyl-4-ylmethoxy)-4-imidazol- 1 -ylmethyl-benzonitrile; 2- (biphenyl-4-yl-2-ethoxy)-4-imidazol- 1-ylmethyl-benzonitrile; 1 -tert-butoxycarbonyl-4-(3chlorophenyl)-2(S)-[2-(2-cyano-5-imidazol- 1-ylmethyl-phenoxy)ethyl]piperazine; 2-(3chlorophenoxy)-4-imidazol- 1 -ylmethyl-benzonitrile; 2-(4-chlorophenyl-2-ethoxy)-4-imidazol- 1 -ylmethyl-benzonitrile; 2-(3-chlorophenyl-2-ethoxy)-4-imidazol- 1-ylmethyl-benzonitrile; 2- (2-chlorophenyl-2-ethoxy)-4-imidazol- 1-ylmethyl-benzonitrile; 2-(phenyl-2-ethoxy)-4imidazol-1I-ylmethyl-benzonitrile; 2-(3-chlorobenzyloxy)-4-imidazol-1I-ylmethyl-benzonitrile; 2-(4-chlorobenzyloxy)-4-imidazol- I -ylmethyl-benzonitrile; 2-(2,4-dichlorobenzyloxy)-4imidazol-1I-ylmethyl-benzonitrile; 2-(benzyloxy)-4-imidazol- 1-ylmethyl-benzonitrile; 2- (biphenyl-2-ylmethoxy)-4-imidazol- I -ylmethyl-benzonitrile; 2-(phenyl-4-butoxy)-4-imidazol- 1 -ylmethyl-benzonitrile; 2-(phenyl-3-propoxy)-4-imidazol-1I-ylmethyl-benzonitrile; 2- (biphenyl-4-yl-2-ethoxy)-4-(1I,2,4-triazol-1I-yl)methyl-benzonitrile; 2-(biphenyl-4-yl-2-ethoxy)- 4-(2-methyl-imidazol- I -yl)methyl-benzonitrile; 2-(biphenyl-4-yl-2-ethoxy)-4-benzimidazol- 1 yl)methyl-benzonitrile; 4-imidazol- 1-ylmethyl-2-(naphthalen-2-yloxy)-benzonitrile; 2-(3cyanophenoxy)-4-imidazol- 1-ylmethyl-benzonitrile; 2-(3-bromophenoxy)-4-imidazol- 1ylmethyl-benzonitrile; 2-(biphen-3-yloxy)-4-imidazol-1I-ylmethyl-benzonitrile; 2-(biphen-4yloxy)-4-imidazol- 1 -ylmethyl-benzonitrile; 2-(3-acetylphenoxy)-4-imidazol- 1 -ylmethyl- __benzonitrile; 2-(2-acetylphenoxy)-4-imidazol- 1 -ylmethyl-benzonitrile; 2-(3o trifluoromethylphenoxy)-4-imidazol- I -ylmethyl-benzonitrile; 2-(3-methylphenoxy)-4-imidazol- 00 1 -ylmethyl-benzonitrile; 2-(2-methylphenoxy)-4-imidazol- 1-ylmethyl-benzonitrile; 2-(4methylphenoxy)-4-imidazol- 1 -ylmethyl-benzonitrile; 2-(3-methoxyphenoxy)-4-imidazol- 1 ylmethyl-benzonitrile; 2-(2-methoxyphenoxy)-4-imidazol-1I-ylmethyl-benzonitrile; 2-(4methoxyphenoxy)-4-imidazol- 1-ylmethyl-benzonitrile; 2-(3 ,5-dimethylphenoxy)-4-imidazol- 1ylmethyl-benzonitrile; 2-(3 ,4-dimethylphenoxy)-4-imidazoi- 1-ylmethyl-benzonitrile; 2-(3 INDdimethoxyphenoxy)-4-imidazol-1I-ylmethyl-benzonitrile; I-naphthyloxy)-4-imidazol- 1ylmethyl-benzonitrile; 2-(2,4-dichlorophenoxy)-4-imidazol-1I-ylmethyl-benzonitrile; 2-(3fluorophenoxy)-4-imidazol- 1-ylmethyl-benzonitrile; 2-(3-t-butylphenoxy)-4-imidazol- 1ylmethyl-benzonitrile; 2- [3-(N,N-diethylamino)phenoxy]-4-imidazol- 1-ylmethyl-benzonitrile; 2-(3 -n-propylphenoxy)-4-imidazol- 1-ylmethyl-benzonitrile; 2-(2,3 -dimethoxyphenoxy)-4imidazol- I -ylmethyl-benzonitrile; 2-(2,3-dimethylphenoxy)-4-imidazol- 1 -ylmethylbenzonitrile; 2-(3 ,4-dimethoxyphenoxy)-4-imidazol-1I-ylmethyl-benzonitrile; 2-(2,5dimethoxyphenoxy)-4-imidazol-1-ylmethyl-benzonitrile; 2-(3,4-dichlorophenoxy)-4-imidazol- 1 -ylmethyl-benzonitrile; 2-(2,4-dimethylphenoxy)-4-imidazol- 1-ylmethyl-benzonitrile; 2-(4chloro-2-methylphenoxy)-4-imidazol- 1-ylmethyl-benzonitrile; 2-(5 -chloro-2-methylphenoxy)- 4-imidazol- 1-ylmethyl-benzonitrile; 2-(2-chloro-4,5-dimethylphenoxy)-4-imidazol- 1-ylmethylbenzonitrile; 2-(5-hydroxymethyl-2-methoxyphenoxy)-4-imidazol-1I-ylmethyl-benzonitrile; 4imidazol- 1-ylmethyl-2-(3-phenylamino-phenoxy)-benzonitrile; 4-imidazo!- 1-ylmethyl-2-[3-(2methylphenylamino)-phenoxy]-benzonitrile; 4-imidazol-1I-ylmethyl-2-(3-phenoxy-phenoxy)benzonitrile; 2-(2-benzoyl-phenoxy)-4-imidazol- 1-ylmethyl-benzonitrile; 1 -(5-chloro-2methoxy-phenyl)-3-[3-(2-cyano-5-imidazol- 1-ylmethyl-phenoxy)-phenyl]-urea; 1 dimethoxy-phenyl)-3-[3-(2-cyano-5-imidazol-1I-ylmethyl-phenoxy)-phenyl]-urea; 2-(3benzyloxy-phenoxy)-4-imidazol- 1-ylmethyl-benzonitri le; 2-(4-benzyloxy-phenoxy)-4imidazol- I -ylmethyl-benzonitrile; 2-(2-benzyl-phenoxy)-4-imidazol- 1 -ylmethyl-benzonitrile; 2- (3-ethynyl-phenoxy)-4-imidazol-1 -ylmethyl-benzonitrile; 2-(4-acetyl-3-methyl-phenoxy)-4imidazol- 1 -ylmethyl-benzonitrile; 4-imidazol- I -ylmethyl-2-( I H-indazol-6-yloxy)-benzonitrile; 4-imidazol- 1-ylmethyl-2-(5 ,6,7,8-tetrahydro-naphthalen- 1-yloxy)-benzonitrile; 4-imidazol- Iylmethyl-2-(8-oxo-5,6,7,8-tetrahydro-naphthalen- 1 -yloxy)-benzonitrile; 4-imidazol- I -ylmethyl- 1 H-indol-7-yloxy)-benzonitrile; 4-imidazol- I -ylmethyl-2-(3-oxo-indan-4-yloxy)benzonitrile; 4-imidazol-1I-ylmethyl-2-( 1H-indol-4-yloxy)-benzonitrile; 2-[3 -(2-hydroxyethoxy)-phenoxy]-4-imidazol- 1-ylmethyl-benzonitrile; 4-imidazol-1I-ylmethyl-2-(4-imidazol- 1yl-phenoxy)-benzonitrile; 4-(2-cyano-5-imidazol- 1-ylmethyl-phenoxy)-biphenyl-4-carbonitrile; N-[3-(2-cyano-5-imidazol- 1-ylmethyl-phenoxy)-phenyl]-acetamide; 4-imidazol- 1-ylmethyl-2o (9-oxo-9H-fluoren-4-yloxy)-benzonitrile; 3-(2-cyano-5-imidazol- 1-ylmethyl-phenoxy)- 00 Nphenyl-benzamide; 3-(2-cyano-5-imidazol- 1-ylmethyl-phenoxy)-N-ethyl-N-phenylbenzamide; 3 -(2-cyano-5 -imidazol-1I-ylmethyl-phenoxy)-N-cyclopropylmethyl-N-phenylbenzamide; 2-(5-chloro-pyridin-3-yloxy)-4-imidazol- 1-ylmethyl-benzonitrile; N-[3-(2-cyano-5- C imidazol- 1 -ylmethyl-phenoxy)-phenyl]-benzenesulfonamide; 4-imidazol- I -ylmethyl-2-(indan- 3-(9H-carbazol-2-yloxy)-4-imidazol-1I-ylmethyl-benzonitrile; 4- IND imidazol- 1 -ylmethyl-2-(5,6,7,8-tetrahydro-naphthalen-2-yloxy)-benzonitrile; 4-imidazol- 1 C) 10 ylmethyl-2-(2-methoxy-4-propenyl-phenoxy)-benzonitrile; 4-imidazol- Il-yI methyl-2- -oxobutyl)-phenoxy]-benzonitrile; 2-(3-chlorophenoxy)-5-imidazol-1I-ylmethyl-benzonitrile; 2-(4chlorophenoxy)-4-imidazol-1I-ylmethyl-benzonitrile; 2-(3,5-dichlorophenoxy)-4-imidazol- 1ylmethyl-benzonitrile; 2-(pyridin-3-yloxy)-4-imidazol-1I-ylmethyl-benzonitrile; 2-(2chlorophenoxy)-4-imidazol-1I-ylmethyl-benzonitrile; 2-(3-chlorophenoxy)-5-(4-phenylimidazol- 1 -ylmethyl)-benzonitrile; 2-(biphen-2-yloxy)-4-imidazol- 1 -ylmethyl-benzonitrile; 2- (phenoxy)-4-imidazol- 1-ylmethyl-benzonitrile; 2-(2-chloro-4-methoxyphenoxy)-4-imidazol- 1ylmethyl-benzonitrile; 2-(2-chlorophenylsulfanyl)-4-imidazol-1I-ylmethyl-benzonitrile; 4imidazol- 1 -ylmethyl-2-(naphthalen-2-ylsulfanyl)-benzonitrile; 2-(2,4-dichlorophenylsulfanyl)- 4-imidazol- 1 -ylmethyl-benzonitrile; 2-(2,4-dichloro-benzenesulfinyl)-4-imidazol- 1 -ylmethylbenzonitrile; 2-(2,4-dichloro-benzenesulfonyl)-4-imidazol-1I-ylmethyl-benzonitrile; 2-(2methyl-pyridin-3-yloxy)-4-imidazol- 1-ylmethyl-benzonitrile; 2-(2,4-dimethyl-pyridin-3-yloxy)- 4-imidazol- 1-ylmethyl-benzonitrile; 2-(4-chloro-2-methoxyphenoxy)-4-imidazol-l1-ylmethylbenzonitrile; 2-(2-chlorophenoxy)-4-(5-methyl-imidazol- 1-ylmethyl)-benzonitrile; 2-(2chlorophenoxy)-4-(4-methyl-imidazol- 1-ylmethyl)-benzonitrile; 2-(3-chloro-5-trifluoromethylpyridin-2-yloxy)-4-imidazol- 1-ylmethyl-benzonitrile; 2-(2,4-dichlorophenoxy)-4-(2-methylimidazol- 1-ylmethyl)-benzonitrile; N-[3-(2-cyano-5-imidazol- 1-ylmethyl-phenoxy)-phenyl]benzamide; 2-[3-(2-cyano-5-imidazol- 1-ylmethyl-phenoxy)-phenyl]-N-phenyl-acetamide; 4imidazol- I -ylmethyl-2-(quinolin-6-yloxy)-benzonitrile; 4-imidazol- 1 -ylmethyl-2-(2-oxo- 1,2dihydro-quinolin-6-yloxy)-benzonitrile; N-[3-(2-cyano-5-imidazol- 1 -ylniethyl-phenoxy)phenyl]-2-phenyl-acetamide; 5-(2-cyano-5-imidazol- 1-ylmethyl-phenoxy)-N-cyclohexylnicotinamide; N-(3-chloro-phenyl)-5-(2-cyano-5-imidazol- 1-ylmethyl-phenoxy)-nicotinamide; 2-(2 ,3 -dimethoxyphenoxy)-4-(2,4-dimethyl-imidazol- 1-ylmethyl)-benzonitri le; 4-(2-methylimidazol- 1 -ylmethyl)-2-(naphthalen-2-yloxy)-benzonitrile; 4-(l1 -imidazol- I -yl-lI -methyl-ethyl)- 2-(naphthalen-2-yloxy)-benzonitrile; I -[4-iodo-3-(naphthalen-2-yloxy)-benzyl]-I1H-imidazole; acetic acid 3-[3-(2-chloro-phenoxy)-4-cyano-benzyl]-3H-imidazol-4-ylmethy ester; 2-(2chloro-phenoxy)-4-(5-hydroxymethyl-imidazol- I -ylmethyl)-benzonitrile; o imidazol- 1-ylmethyl)-2-(2-chloro-phenoxy)-benzonitrile; N-({3-[4-cyano-3 -(2,3-dimethoxy- 00 phenoxy)-benzyl]-3 H-imidazol-4-ylmethyl }-2-cyclohexyl-acetamide; 2-(3 -chloro-phenoxy)-4- [(4-chloro-phenyl)-imidazol- 1-yl-methyl]-benzonitrile; 2-(3-chloro-phenoxy)-4-[ 1-(4-chlorophenyl)-2-hydroxy- I -imidazol- 1 -yl-ethyl]-benzonitrile; 2-(3-chloro-phenoxy)-4-[(4-chlorophenyl)-hydroxy-(3 1--imidazol-4-yl)-methyl]-benzonitrile; 2-(2,4-dichloro-phenylsulfanyl)-4- [5-(2-morpholin-4-yl-ethyl)-imidazol- I -ylmethyl]-benzonitrile; 2-(2,4-dichloro-phenoxy)-4-[5- IND ~(2-morphol in-4-yl -ethyl)- imidazol- 1 -ylmethyl] -benzonitri le; 4-[hydroxy-(3-methyl-3H- 0 iiao--l-ehl--nptae--lx)bnoirl;4[mn-3mty- -mdz C)1 iizl4-yl)-methyl]-2-(naphthalen-2-yloxy)-benzonitrile; 4-[aI-hdrxy 1-(3-methyl-3H-imidazol- 4y)-ethyl]-2-(naphthalen-2-yloxy)-benzonitrile; -ino--(3-methyl-3 H-imidazol-4ethyl] -2-(naphthalen-2-yloxy)-benzonitrile hydrochloride; 3- {2-cyano-5-[] -amino- I -(3-methyl- 3 H-imidazol-4-yl)-ethyl]-phenoxy} -N-ethyl-N-phenyl-benzamide; 3- {2-cyano-5-[ 1-hydroxy- 1- (3-mcthyl-3 H-imidazol-4-yl)-ethyl]-phenoxy} -N-ethyl-N-phenyl-benzamide; 1-hydroxy- 1- (3-methyl-3H-imidazol-4-yl)-ethyl]-2-(3-phenylamino-phenoxy)-benzonitrile; I-hydroxy- 1- (3 -methyl-3 H-imidazol-4-yl)-ethyl]-2-(3-phenoxy-phenoxy)-benzonitrile; 2-(3 -benzoylphenoxy)-4-[ 1-hydroxy-l1-(3-methyl-3 H-imidazol-4-yl)-ethyl]-benzonitrile; 2-(3-tert-butylphenoxy)-4-[ I-hydroxy- 1-(3-methyl-3H-imidazol-4-yl)-ethyl]-benzonitrile; 2-(3-diethylaminophenoxy)-4-[ 1-hydroxy-1I-(3-methyl-3H-imidazol-4-yl)-ethyl]-benzonitrile; 2-(5-chloro-2-oxo- 2H-[ 1,2']bipyridinyl-5 '-ylmethoxy)-4-imidazol-1I-ylmethyl-benzonitrile; 4-Imidazol- 1ylmethyl-2-[2-(2-oxo-2H-pyridin- 1-yl)-phenoxy]-benzonitrile; 4-Imidazol- 1-ylmethyl-2-[3-(2oxo-2H- pyridin- 1 -yl)-phenoxy]-benzonitrile; 4-Imidazol- I -ylmethyl-2-[4-(2-oxo-2Hpyridin- 1 -yl)-phenoxy]-bcnzonitrile; 4-imidazol- I -ylmethyl-2-[3-(2-oxo-piperidin- Il-yI)phenoxy]-benzonitrile; 4-imidazol-1I-ylmethyl-2-[4-(2-oxo-piperidin-1I-yl)-phenoxy]benzonitrile; 4-imidazol- 1-ylmethyl-2-[2-(3 -methyl-2-oxo-piperidin- 1-yl)-phenoxy]benzonitrile; 4-imidazol-1I-ylmethyl-2-(3-morpholin-4-yl-phenoxy)-benzonitrile; 4-imidazol- 1ylmethyl-2-(3-piperidin- 1-ylmethyl-phenoxy)-benzonitrile; ,3-dimethyl-2-oxo-piperidin- 1 -yl)-phenoxy] -4-imidazol-1I-ylmethyl-benzonitrile; 2- [3 -ethyl- 1 -methyl-2-oxo-azepan-3 yI)-phenoxy]-4-imidazol-1I-ylmethyl-benzonitrile; 2- [3 -ethyl- I -methyl-2-oxo-azepan-3 -yl)phenoxy]-4-(2-methyl-imidazol- 1-yl)methyl-benzonitrile; 2-[3-(3-ethyl-l1-methyl-2-oxoazepan-3-yI)-phenoxy]-4-(5-methyl-imidazol-1I-yI)methyl-benzonitrile; 2- [3 -ethyl- 1 -methyl- 2-oxo-azepan-3-yI)-phenoxy]-4-(2,5-dimethyl-imidazol-1I-yl)methyl-benzonitrile; 2-[3-(3-ethyl- 1 -methyl-2-oxo-azepan-3-yl)-phenoxy] 1,2,4]triazol-4-ylmethyl-benzonitrile; 2-[3-(3-ethyl- IND 193 I -methyl-2-oxo-azepan-3 -yl)-phenoxy]-4-[1I,2,4]triazol-1I-ylmethyl-benzonitrile; 4-imidazol- 1ylmethyl-2-[3-( I-methyl-2-oxo-azepan-3-yl)-phenoxy]-benzonitrile; 4-imidazol-lI-ylmethyl-2o [3 -methyl-2-oxo-azocan-3 -yI)-phenoxy]-benzonitrile; 4-imidazol- 1 -ylmethyl-2-[3 00 methyl-2-oxo-piperidin-3-yl)-phenoxy]-benzonitrile; 4-imidazol- I -ylmethyl-2- [3 -ethyl- 1 methyl-2-oxo-piperidin-3-yl)-phenoxy]-benzonitrile; 4-imidazol- 1-ylmethyl-2-[3-(2-oxoazepan-3 -y1)-phenoxy] -benzonitrile; 2-[3 -(3-hydroxymethyl-l1-methyl-2-oxo-azepan-3 -yl)phenoxy]-4-imidazol-1I-ylmethyl-benzonitrile; 2-[3-(3-cyclopropylmethyl-l1-methy1-2-oxoazepan-3-yl)-phenoxy]-4-imidazol-1I-ylmethyl-benzonitrile; 2-[4-bromo-3-(3- INDcyclopropylmethyl- 1 -methyl-2-oxo-azepan-3 -yl)-phenoxy] -4-imidazol- 1 -ylmethyl-benzonitrile; 2- [3 -methoxymethyl- I -methyl-2-oxo-azepan-3 -yl)-phenoxy] -4-imidazol- I -ylmethylbenzonitrile; 2-[3-(3-ethyl-2-oxo-azepan-3-yl)-phenoxy]-4-imidazol-1I-ylmethyl-benzonitrile; 2- [3-(3-ethyl-azepan-3 -yl)-phenoxy]-4-imidazol-1I-ylmethyl-benzonitrile; I-acetyl-3 -ethylazepan-3-yI)-phenoxy]-4-imidazol-1I-ylmethyl-benzonitrile; 3-[3-(2-cyano-5-imidazol- Iyl methyl-phenoxy)-phenyl] -3 -ethyl -azepane- 1 -carboxyl ic acid-tert-butyl ester; 4- [5 -(2-aminoethyl)-2-methyl-imidazol- 1 -ylmethyl] -ethyl- 1 -methyl-2-oxo-azepan-3 -yl)-phenoxy] benzonitrile; 2- [3 -ethyl- 1 -methyl-2 -oxo-azepan-3 -yl)-phenoxy] [2-methylI- 5- (2-morphol in- 4-yl-ethyl)-imidazol- I -ylmethyl]-benzonitrile; {4-cyano-3 -ethyl- I -methyl-2-oxoazepan-3-yl)-phenoxy] -benzyl)}-2-methyl-3H-imidazol-4-yl)-ethyl]-acetamide; 3-ethyl-3 imidazol- 1 -ylmethyl-phenoxy)-phenyl]- 1 -methyl-azepan-2 -one; 2-[3-(3-ethyl- 1 -methyl-2-oxo- 0 azepan-3-yl)-phenoxy] -4-(3-methyl-3-H-imidazol-4-ylmethyl)-benzonitrile; 2-[3-(3-ethyl- 1methyl-2-oxo-azepan-3 -yI)-phenoxy]-4-(3 H-imidazol-4-ylmethyl)-benzonitrile; 2-[3-(3-ethyl- 1methyl-2-oxo-azepan-3 -yI)-phenoxy] [hydroxy-(3 -methyl-3 -H-imidazol-4-yI)-methyl] benzonitrile; 4-[amino-(3 -methyl-3 -H-imidazol-4-yi)-methyl] -ethyl- I -methyl-2-oxoazepan-3 -yi)-phenoxy] -benzonitrile; 2- [3 -(3-ethyl- I -methyl-2-oxo-azepan-3 -yI)-benzyl] methyl-3H-imidazole-4-carbonyl)-benzonitrile; 2-[3-(3-ethyl- 1 -methyl-2-oxo-azepan-3-yl)phenoxy] -4-(hydroxy-pyridin-3 -yl-methyl)-benzonitri le; 2- [3 -(3-ethyl-i -methyl-2-oxo-azepan- 3-yl)-phenoxy]-4-pyridin-3-ylmethyl-benzonitrile; 2- [3 -ethyl- I -methyl-2-oxo-azepan-3 -yl)phenoxy]-4-pyridin-2-ylmethyl-benzonitrile; 2- [3 -ethyl- I -methyl-2-oxo-azepan-3 -yl)phenoxy]-4-[ 1-hydroxy-l1-(3 -methyl-3H-imidazol-4-yl)-ethyl]-benzonitrile; 2-[3-(3-ethyl- 1methyl-2-oxo-azepan-3-yl)-phenoxy]-4-[ 1-amino- I -(3-methyl-3 H-imidazol-4-yl)-ethyl]benzonitrile; 1 -(4'-Cyanobenzyl) imidazol-5-ylmethyl]-4-[ 1-phenyl- 1eyeclopentylcarbonyl] piperazine; 1 -(4'-Cyanobenzyl) imidazol-5-ylmethyl]-4- [Cyclohexylphenylacetyllpiperazine; 1 1 -(4'-Cyanobenzyl) imidazol-5-ylmethyl]-4-[ 1-(3methoxyphenyl)-lI-cyclopentylcarbonyllpiperazine; 1-El -(4'-Cyanobenzyl) ylmethyl]-4-[ 1-(3-phenoxyphenyl)-l1-cyclopentylcarbonyl]piperazine; 1-ri -(4'-Cyano-3fluorobenzyl) imidazol-5-ylmethyl]-4-[ 1-(3-hydroxyphenyl)-lI-cyclohexylcarbonyl]piperazine; o 1-[i -(4'-Cyanobenzyl) imidazol-5-ylmethyl]piperazine-4-carboxylic acid-(2,6- 00 dimethoxy)benzyl ester; 1j -I -(4'-Cyanobenzyl) imidazol-5-yimethyl]piperazine-4-(DL-2hydroxy-2-(o-methoxyphenyl)) acetamide; 1-ri -(4'-Cyanobenzyl) imidazol-5-ylmethyl]-4-[ 1- (2,6-dimethylbenzyloxycarbonyl]piperazine; 1-[i -(4'-Cyanobenzyl) imidazoi-5-ylmethyl]-4-[ 1- (2-methoxyphenyl)-l1-cyclopentylcarbonyl]piperazine; i-[i -(4'-Cyanobenzyl) ylmethyl]-4-[ 1 -(bicyclo[3. 1 .0]hex-3-yl)- 1 -(3-methoxyphenyl)-carbonyl]piperazine; 2 [4- 1-10((Phenyl)methyloxycarbonyl-lI-piperazine)]-2-[ 1-(4'-cyanobenzyl)-2-methyl-5imidazol]acetonitrile; 1-[i -(4'-methylbenzyi) imidazol-5-ylmethyl]-4-[ 1-(2,6dimethylbenzyloxycarbonyl]piperazine; 1-[i -(4'-Cyanobenzyl) ylmethyl]piperazine-4-carboxylic acid-(4-nitro)phenyl ester; 1 -(4-Cyanobenzyl) ylmethyl]-4-r3-(4-fluorophenyl)-3-(tricyclo[3 .3.1 .13 7 ]dec-2-yl)-propionyl]piperazine; cyanobenzyi)imidazol-5-yl-2-[4-(phenylmethyioxy carbonyl)piperazin-lI-yl]acetamide; 1-[i (4'-cyanobenzyl) imidazol-5-ylmethyl]-4-[ chilorobenzyloxycarbonyl ]piperazi ne; 1-[i -(4'-cyanobenzyl) imidazol-5-ylmethyl]-4-r 1- (pentafluororobenzyloxycarbonyl]piperazine; 1-ri -(4'-cyanobenzyl) imidazol-5-ylmethyl]-4-[ 1- (2-ethoxybenzyloxycarbonyl]piperazine; i-ri -(4'-cyanobenzyl) imidazol-5-ylmethyl]-4- methoxypyridin-3 -yI)methyioxycarbonyl])}piperazine; 1- '-cyanobenzyl) imidazol-5 ylmethyl]-4-[ 1-(2-trifluoromethoxybenzyloxycarbonyl]piperazine; i-ri -(4'-cyanobenzyl) imidazol-5-ylmethyl]-4-[ I-(2,3-methylenedioxybenzyloxycarbonyl]piperazine; 1-[i Cyanobenzyl) imidazol-5-ylmethyl]piperazine-4-carboxylic acid benzyl ester; i-ri1 Cyanobenzyl) imidazol-5-ylmethyl]-piperazine-3-carboxylic acid-4-carboxylic acid benzyl ester; i-[I '-Cyanobenzyl) imidazol-5-ylmethyl] -3-methyl carboxy-piperazine-4-carboxylic acid, or a stereoisomeric form, or a pharmaceutically acceptable acid or base addition salt form thereof, in a therapeutically effective amount.

In one embodiment, the compound may be one or more of the following: 1-(3- Chlorophenyl) 1-(4-cyanobenzyl)-5 -imidazol ylImethyl ]-2-piperazi none; 1-(3- Chlorophenyl)-4-[ 1-(4-cyanobenzyi)-5-imidazoiyimethyi]-5-[2-(ethanesulfonyl)methyl]-2piperazinone; 4-ri -(5-Chloro-2-oxo-2H-[ I ,2']bipyridinyl-5 '-yimethyl)- I H-pyrrol-2-ylmethyl]benzonitrile and 1 1 -(4-cyanobenzyl)-5-imidazolylmethyl)-N-(4-cyanobenzyl)amino]-4- (phenoxy)benzene, or a stereoisomeric form, or a pharmaceutically acceptable acid or base addition salt form thereof, in a therapeutically effective amount.

I

ID

o In another aspect, the invention provides a method of treating a synucleinopathic subject S by administering a one or more farnesyl transferase inhibitor compounds described in US Pat O No. 5,919,785 and US Pat No. 5,859,012 (the disclosures of which are incorporated herein by OO reference) or a stereoisomeric form, or a pharmaceutically acceptable acid or base addition salt form thereof, in a therapeutically effective amount.

In another aspect, the invention provides a method of treating a synucleinopathic subject O by administering a farnesyl transferase inhibitor compound of the formula: C C O u

N

or a stereoisomeric form, or a pharmaceutically acceptable acid or base addition salt form thereof, in a therapeutically effective amount.

In one aspect of the invention the synucleinopathic subject has a synucleinopathy selected from the group consisting of: Parkinson's disease, diffuse Lewy body disease, and multiple system atrophy disorder. In a preferred embodiment the subject is a human.

In certain embodiments of the invention the effective amount of the compound of the invention comprises about 10 ng/kg of body weight to about 1000 mg/kg of body weight at a frequency of administration from once a day to once a month. In one embodiment the invention comprises further administering to the subject an amount of one or more non-farnesyl transferase inhibitor compounds effective to treat a neurological disorder. In one embodiment of the invention each non-famesyl transferase inhibitor compound is selected from the group consisting of: dopamine agonist, DOPA decarboxylase inhibitor, dopamine precursor, monoamine oxidase blocker, cathechol 0-methyl transferase inhibitor, anticholinergic, and NMDA antagonist. In one embodiment of the invention each non-farnesyl trasferase inhibitor compound is selected from the group consisting of Memantine, Aricept, and other acetylcholinesterase inhibitors.

Another aspect of the invention provides an article of manufacture comprising packaging material and a farnesyl transferase inhibitor compound, wherein the article of manufacture further comprises a label or package insert indicating that the farnesyl transferase

ID

O inhibitor compound can be administered to a subject for treating a synucleinopathy. In a S preferred embodiment the subject is a human. In one embodiment the invention comprises O further administering to the subject an amount of one or more non-farnesyl transferase inhibitor 00 compounds effective to treat a neurological disorder. In one embodiment of the invention each non-farnesyl transferase inhibitor compound is selected from the group consisting of: dopamine agonist, DOPA decarboxylase inhibitor, dopamine precursor, monoamine oxidase blocker, cathechol 0-methyl transferase inhibitor, anticholinergic, and NMDA antagonist. In one c embodiment of the invention each non-famesyl trasferase inhibitor compound is selected from ND the group consisting of Memantine, Aricept, and other acetylcholinesterase inhibitors.

In methods of the invention, the term "synucleinopathic subject" refers to a subject that is affected by or at risk of developing a synucleinopathy predisposed, for example genetically predisposed, to developing a synucleinopathy) and/or any neurodegenerative disorders characterized by pathological synuclein aggregations. Several neurodegenerative disorders including Parkinson's Disease, Diffuse Lewy Body disease (DLBD) and Multiple System Atrophy (MSA) are collectively grouped as synucleinopathies.

Synucleins are small proteins (123 to 143 amino acids) characterized by repetitive imperfect repeats SEQ ID NO: 8 (KTKEGV) distributed throughout most of the amino terminal half of the polypeptide in the acidic carboxy-terminal region. There are three human synuclein proteins termed a, 0, and y, and they are encoded by separate genes mapped to chromosomes 4221.3-q22, 5q23 and 10q23.2-q23.3, respectively. The most recently cloned synuclein protein synoretin, has a close homology to y-synuclein and is predominantly expressed within the retina. a-synuclein, also referred to as non-amyloid component of senile plaques precursor protein (NACP), SYN1 or synelfin, is a heat-stable, "natively unfolded" protein of poorly defined function. It is predominantly expressed in the central nervous system (CNS) neurons where it is localized to presynaptic terminals. Electron microscopy studies have localized asynuclein in close proximity to synaptic vesicles at axonal termini, suggesting a role for asynuclein in neurotransmission or synaptic organization, and biochemical analysis has revealed that a small fraction of a-synuclein may be associated with vesicular membranes but most asynuclein is cytosolic.

Genetic and histopathological evidence supports the idea that a-synuclein is the major component of several proteinaceous inclusions characteristic of specific neurodegenerative diseases. Pathological synuclein aggregations are restricted to the a-synuclein isoforms, as P and y synucleins have not been detected in these inclusions. The presence of a-synuclein positive aggregates is disease specific. Lewy bodies, neuronal fibrous cytoplasmic inclusions

\D

S that are histopathological hallmarks of Parkinson's Disease (PD) and Diffuse Lewy Body disease (DLBD) are strongly labeled with antibodies to a-synuclein. Dystrophic ubiquitin- O positive neurites associated with PD pathology, termed Lewy neurites (LN) and CA2/CA3 00 ubiquitin neurites are also a-synuclein positive. Furthermore, pale bodies, putative precursors of LBs, thread-like structures in the perikarya of slightly swollen neurons and glial silver positive inclusions in the midbrains of patients with LB diseases are also immunoreactive for asynuclein. a-synuclein is likely the major component of glial cell inclusions (GCIs) and neuronal cytoplasmic inclusions in MSA and Hallervorden-Spatz disease (brain iron accumulation type a-synuclein immunoreactivity is present in some dystrophic neurites in C 10 senile plaques in Alzheimer's Disease, but is not detected in Pick bodies neurofibrillary tangles (NFTs), neurophil threads, or in neuronal or glial inclusion characteristic of Progressive Supranuclear Palsy, Corticolbasal Degeneration, motor neuron disease and trinucleotide-repeat diseases.

Further evidence supports the notion that a-synuclein is the actual building block of the fibrillary components of LBs, LNs and GCIs. Immunoelectron microscopic studies have demonstrated that these fibrils are intensely labeled with a-synuclein antibodies in situ.

Sarcosyl-insoluble a-synuclein filaments with straight and twisted morphologies can also be observed in extracts of DLBD and MSA brains. Moreover, a-synuclein can assemble in vitro into elongated homopolymers with similar widths as sarcosyl-insoluble fibrils or filaments visualized in situ. Polymerization is associated with a concomitant change in secondary structure from random coil to anti-parallel P-sheet structure consistent with the Thioflavine-S reactivity of these filaments. Furthermore, the PD-association with a-synuclein mutation, A53T, may accelerate this process, as recombinant A53T a-synuclein has a greater propensity to polymerize than wild-type a-synuclein. This mutation also affects the ultrastructure of the polymers; the filaments are slightly wider and are more twisted in appearance, as if assembled from two protofilaments. The A30P mutation may also modestly increase the propensity ofasynuclein to polymerize, but the pathological effects of this mutation also may be related to its reduced binding to vesicles. Interestingly, carboxyl-terminally truncated a-synuclein may be more prone to form filaments than the full-length protein.

According to the invention, the proteosomal degradation of a-synuclein is a mediated by parkin and neuronal ubiquitin C-terminal hydrolase (UCH-L1). Parkin is an E3 ligase that ubiquitinylates a-synuclein and thereby tags it for degradation. UCH-L1 acts in normal neuronal tissues to cleave the ubiquitinylated proteins that are products of the proteosomal degradation of the polyubiquitinylated proteins.

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O The invention provides methods for treating synucleinopathic disorders using inhibitors S of famesyl transferase. It has been now discovered that UCH-L1 is famesylated in vivo. UCH- O LI is associated with the membrane and this membrane association is mediated by 00 farnesylation. Farnesylated UCH-L1 also stabilizes the accumulation of a-synuclein. The invention relates to the prevention or inhibition of UCH-L1 farnesylation which would result in UCH-L1 membrane disassociation and acceleration of the degradation of a-synuclein. Since a- O synuclein accumulation is pathogenic in PD, DLBD, and MSA, an increased degradation of ac synuclein and/or inhibition of a-synuclein accumulation ameliorates the toxicity associated with \O a pathogenic accumulation of a-synuclein.

0 10 The modification of a protein by a farnesyl group can have an important effect on function for a number of proteins. Famesylated proteins typically undergo further C-terminal modification events that include a proteolytic removal of three C-terminal amino acids and carboxymethylation of C-terminal cystines. These C-terminal modifications facilitate proteinmembrane association as well as protein-protein interactions. Farnesylation is catalyzed by a protein farnesyltransferase (FTase), a heterodimeric enzyme that recognizes the CAAX motif present at the C-terminus of the substrate protein. FTase transfers a farnesyl group from farnesyl pyrophosphate and forms a thioether linkage between the famesyl and the cystine residues in the CAAX motif. A number of inhibitors of FDase have been developed and are known in the art. However, the invention provides novel methods for using certain farnesyl .0 transferase inhibitors to treat subjects having symptoms associated with a-synuclein accumulation.

In methods of the invention, the term "synucleionopathy" refers to neurological disorders that are characterized by a pathological accumulation of a-synuclein. This group of disorders includes PD, DLBD and MSA.

Parkinson's Disease (PD) is a neurological disorder characterized by bradykinesia, shuffling gait, postural instability, tremor, and a loss of automatic movement. It is due to the loss of dopamine-containing substantia nigra cells. It appears that about 50% of the cells need to be lost before symptoms appear. Associated symptoms often include rigidity, difficulty initiating movement (akinesia), small handwriting (micrographia), seborrhea, orthostatic hypertension, urinary difficulties, constipation, lymph pain, depression, dementia (up to a third of the patients), smelling disturbances (occurs early). Orthostatic hypertension might occur associated with the disease or as a complication of medication. Patients with Parkinsonism have greater mortality, about two times compared to general population without PD. This is attributed to greater frailty or reduced mobility.

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0 The term "synucleinopathic subject" encompasses a subject that is affected by, or is at risk of developing PD. These subjects can be readily identified by persons of ordinary skill in S the art by symptomatic diagnosis or by genetic screening, brain scans, SPEC, PET imaging etc.

00 Diagnosis of PD is mainly clinical and is based on the clinical findings listed above.

There are many conditions which may be mistaken for Parkinsonism. Among the most common are side effects of drugs, mainly the major tranquilizers, such as Haldol, strokes Sinvolving the basal ganglea, degenerative disorders, such as progressive supranuclear palsy (PSP), olivopontocerebellar degeneration (OPCD), MSA, and Huntington's Disease. The \pathological hallmark of PD are Lewy bodies, which are intracytoplasmatic inclusion bodies in effected neurons of the substantion nigra. Recently, a-synuclein has been identified as the main component of Lewy bodies in sporadic Parkinsonism.

Although Parkinson's can be clearly traced to genetic factors, viruses, stroke, or toxins in few individuals for the most part the cause of Parkinson's in any particular case is unknown (this is referred to as sporadic PD). Environmental influences include drinking well water, farming and industrial exposure to heavy metals (iron, zinc, copper, mercury, magnesium and manganese), alkylated phosphates and orthonal chlorines. Paraquat (a herbicide) has been associated with increased prevalence of Parkinsonism, cigarette smoking is associated with the decrease incidence. The current consensus is that Parkinsonism may either be caused by an uncommon toxin combined with high genetic susceptibility or a common toxin combined with relatively low genetic susceptibility.

Subjects that are at risk of developing PD can be identified for example by genetic analysis. There is good evidence for genetic factors associated with PD. Large pedigrees of autosomal dominantly inherited PDs have been reported. A mutation in a-synuclein is responsible for one pedigree.

Methods of the invention can be used in combination with one or more alternative medications, including medications that are currently used to treat synucleinopathies or symptoms arising as side-effects of the disease or of the aforementioned medications.

For example, methods of the invention can be used in combination with medications for treating PD. Levodopa mainly in the form of combination product containing carbodopa and levodopa (Synemat and Synemat CR) is the mainstay of treatment and is the most effective agent for the treatment of PD. Levodopa is a dopamine precursor, a substance that is converted into dopamine by an enzyme in the brain. Carbodopa is a peripheral dicarboxylase inhibitor which prevents side effects and lower the overall dosage requirement. The starting dose of Synemat is 125/100 tablet prior to each meal. User maintenance dose is lower. Dyskinesias 200 S may result from overdose and also are commonly seen after prolonged years) use. Direct acting dopamine agonists may have less of this side effect. Orthostatic hypertension may o respond to increased carbodopa. About 15% of patients do not respond to levodopa. Dopamine 00 is metabolized to potentially toxic-free radicals and some feel that a direct-acting dopamine agonist should be used early to supplement a dopamine agonist. Stalevo (carbodopa, levodopa, and entacapone) is a new combination tablet for patients who experience signs and symptoms O of"wearing-off'. The tablet combines carbodopa, levodopa, (the most widely agents for PD) c with entacapone, while carbodopa reduces the side effects of levodopa, entacapone extends the ,O time levodopa is active in the brain, up to 10% longer.

0 10 Amantidine (Symmetrel) is a mild agent thought to work by blocking the re-uptake of dopamine into presynaptic neurons. It also activates the release of dopamine from storage sites and has a glutamate receptor blocking activity. It is widely used as early monotherapy and the dosing is 200 to 300 mg daily. Amantidine is particularly helpful in patients with predominant tremor. Side effects include ankle swelling and red blotches. Unfortunately, it's effect in more advanced PD is often short-lived with patients reporting a "fallout effect".

Anticholinergics (trihexyphenidyl, benztropine mesylate, procyclidine, artane, cogentin) do not act directly on the dopaminergic system. Direct-acting dopamine agonists include bromocriptidine (Parlodel), pergolide (Permax), ropinirol (Requip), and pramipexole (Mirapex).

These agents cost substantially more than the levodopa (Synemat) with controversial additional benefits. Depending on which dopamine receptor is being stimulated, DI and D2 agonist can exert anti-Parkinson effects by stimulating the Dl and D2 receptors, such as Ergolide. Mirapex and Requip are the newer agents. Both are somewhat selected for dopamine receptors with highest affinity for the D2 receptor and also activity at the D3 receptor. Direct dopamine agonists, in general, are more likely to produce adverse neuro psychiatric side effects than levodopa, such as confusion. Unlike levodopa, direct dopamine agonists do not undergo conversion to dopamine and thus do not produce potentially toxic metabolites. It is also possible that the early use of direct dopamine agonist might protect against the development of late complications of dopamine, such as the "on-off' effect.

Monoaminoxidase-B inhibitors (MAO) such as selegiline (Diprenyl, or Eldepryl), taken in a low dose, can initially reduce the progression of Parkinsonism. These compounds can be used as an adjunctive medication. A study has documented that selegiline delays the need for levodopa by roughly three months.

Catechol-O-methyltransferase inhibitors (COMT) can also be used in combination treatments of the invention. Catechol-O-methyltransferase is an enzyme that degrades levodopa

NO

and inhibitors can be used to reduce the rate of degradation. Entocapone is a peripherally acting S COMT inhibitor, which can be used in certain methods and compositions of the invention.

O Tasmar or Tolcapone, approved by the FDA in 1997, can also be used in certain methods and 00 compositions of the invention. Psychiatric adverse effects that are induced by PD medication include psychosis, confusion, agitation, hallucinations, and delusions. These can be treated by decreasing dopamine medication, reducing or discontinuing anticholinergics, amantidine or O selegiline or by using clozipine, for example at doses of 6.25 to 50 mg/day.

Methods of the invention can also be used in combination with surgical therapies for the ,O treatment of PD. Surgical treatment is presently recommended for those who have failed

O

0 10 medical management of PD. Unilateral Thallamotomy can be used to reduce tremor. It is considered for patients with unilateral tremor not responding to medication. The improvement fades with time. Bilateral procedures are not advised. Unilateral pallidotomy is an effective technique for reducing contralateral levodopamine dyskinesias. Unilateral deep brain stimulation of the thalamus for tremor may also be a benefit for tremor. Neurotransplantation is no longer felt to be an effective treatment. Gamma knife surgery thalamotomy or pallidotomy can be performed to focus radiation. In addition to surgery and medication, physical therapy in Parkinsonism maintains muscle tone, flexibility, and improves posture and gait.

According to the invention, the term "synucleinopathic subject" also encompasses a subject that is affected by, or is at risk of developing DLBD. These subjects can be readily identified by persons of ordinary skill in the art by symptomatic diagnosis or by genetic screening, brain scans, SPEC, PET imaging etc.

DLBD is the second commonest cause of neurodegenerative dementia in older people, it effects 7% of the general population older than 65 years and 30% of those aged over 80 years.

It is part of a range of clinical presentations that share a neurotic pathology base of normal aggregation of the synaptic protein a-synuclein. DLBD has many of the clinical and pathological characteristics of the dementia that occurs during the course of Parkinson's Disease. An "one year rule" can been used to separate DLBD from PD. According to this rule, onset of dementia within 12 months of Parkinsonism qualifies as DLBD, whereas more than 12 months of Parkinsonism before onset of dementia qualifies as PD. The central features of DLBD include progressive cognitive decline of sufficient magnitude to interfere with normal social and occupational function. Prominent or persistent memory impairment does not necessarily occur in the early stages, but it is evident with progression in most cases. Deficits on tests of attention and of frontal cortical skills and visual spatial ability can be especially prominent.

202 O Core diagnostic features, two of which are essential for diagnosis of probable and one for possible DLBD are fluctuating cognition with pronounced variations in attention and O alertness, recurrent visual hallucinations that are typically well-formed and detailed, and 00 spontaneous features of Parkinsonism. In addition, there can be some supportive features, such as repeated falls, syncope, transient loss of consciousness, neuroleptic sensitivity, systematized delusions, hallucinations and other modalities, REM sleep behavior disorder, and depression.

l Patients with DLBD do better than those with Alzheimer's Disease in tests of verbal memory, but worse on visual performance tests. This profile can be maintained across the range of ,O severity of the disease, but can be harder to recognize in the later stages owing to global

O

0 10 difficulties. DLBD typically presents with recurring episodes of confusion on a background of progressive deterioration. Patients with DLBD show a combination of cortical and subcortical neuropsychological impairments with substantial attention deficits and prominent frontal subcortical and visual special dysfunction. These help differentiate this disorder from Alzheimer's Disease.

Rapid eye movement (REM), sleep behavior and disorder is a parasomnia manifested by vivid and frightening dreams associated with simple or complex motor behavior during REM sleep. This disorder is frequently associated with the synucleinopathies, DLBD, PD and MSA, but it rarely occurs in amyloidopathies and taupathies. The neuropsychological pattern of impairment in REM sleep behavior disorder/dementia is similar to that reported in DLBD and qualitatively different from that reported in Alzheimer's Disease. Neuropathological studies of REM sleep behavior disorder associated with neurodegenerative disorder have shown Lewy body disease or multiple system atrophy. REM sleep wakefulness disassociations (REM sleep behavior disorder, daytime hypersomnolence, hallucinations, cataplexy) characteristic of narcolepsy can explain several feature of DLBD, as well as PD. Sleep disorders could not contribute to the fluctuations typical of DLBD and their treatment can improve fluctuations and quality of life. Subjects at risk of developing DLBD can be identified. Repeated falls, syncope, transient loss of consciousness, and depression are common in older people with cognitive impairment and can serve as (a red flag) to a possible diagnosis of DLBD. By contrast, narcoleptic sensitivity in REM sleep behavior disorder can be highly predictive of DLBD.

Their detection depends on the clinicians having a high index of suspicion and asking appropriate screening questions.

Clinical diagnosis of synucleinopathic subjects that are affected by or at risk of developing LBD can be supported by neuroimaging investigations. Changes associated with DLBD include preservation of hippocampal, and medialtemperalobe volume on MRI and sipital 203 hyperprofusion on SPECT. Other features, such as generalized atrophy, white medichanges and N rates of progression of whole brain atrophy are not helpful in differential diagnosis. Dopamine O transported a loss in the caudate and putamen, a marker of nigrostriatal degeneration can be OO detected by dopomenergic SPECT and can prove helpful in clinical differential diagnosis. A sensitivity of 83% and specificity of 100% has been reported for an abnormal scan with an autopsy diagnosis of DLBD.

O Consensus criteria for diagnosing DLBD include ubiquitin immunohistochemistry for c Lewy body identification and staging into three categories; brain stem predominant, limbic, or \neocortical, depending on the numbers and distribution of Lewy bodies. The recently-

O

0 10 developed a-synuclein immunohistochemistry is a better marker that visualizes more Lewy bodies and also better source previously under recognized neurotic pathology, termed Lewy neurites. Use of antibodies to a-synuclein moves the diagnostic rating for many DLBD cases from brain stem and limbic groups into the neocortical group.

In most patients with DLBD, there are no genetic mutations in the a-synuclein or other Parkinson's Disease genes. Pathological up-regulation of normal, wild-type a-synuclein due to increased mRNA expression is a possible mechanism, or Lewy bodies may form because asynuclein becomes insoluble or more able to aggregate for some reason. Another possibility is that a-synuclein is abnormally processed, for example, by dysfunctional proteosome system and that toxic "proto fibrils" are therefore produced. Sequestering of these toxic fibrils into Lewy bodies could reflect an effort by the neurons to combat biological stress inside the cell, rather than their simply being neurodegenerative debris.

Target symptoms for the accurate of DLBD can include extrapyramidal motor features, cognitive impairment, neuropsychiatric features (including hallucinations, depression, sleep disorder, and associated behavioral disturbances) or autonomic dysfunction.

Methods of the invention can be used in combination with one or more alternative medications for treating DLBD. For example, lowest acceptable doses of levodopa can be used for treating DLBD. D2-receptor antagonists, particularly traditional neuroleptic agents can provoke severe sensitivity reactions in DLBD subjects with an increase in mortality of two to three times. Cholinsterase inhibitors dicussed above are also used in the treatment of DLBD.

According to the invention, the term "synucleinopathic subject" also encompasses a subject that is affected by, or is at risk of developing MSA. These subjects can be readily identified by persons of ordinary skill in the art by symptomatic diagnosis or by genetic screening, brain scans, SPEC, PET imaging etc.

MSA is a neurodegenerative disease marked by a combination of symptoms; affecting

\O

movement, blood pressure, and other body functions, hence the label "multiple system S atrophy". The cause of MSA is unknown. Symptoms of MSA vary in distribution of onset and severity from person to person. Because of this, three different diseases were initially described 00 to accomplish this range of symptoms; Shy-Drager syndrome, striatonigral degeneration (SD), and olivopontocerebellar atrophy (OPCA).

In Shy-Drager syndrome, the most prominent symptoms are those involving the O autonomic system; blood pressure, urinary function, and other functions not involving Cc conscious control. Striatonigral degeneration causes Parkinsonism symptoms, such as slowed O movements and rigidity, while OPCA principally effects balance, coordination and speech. The symptoms for MSA can also include orthostatic hypertension, male impotence, urinary difficulties, constipation, speech and swallowing difficulties, and blurred vision.

The initial diagnosis of MSA is usually made by carefully interviewing the patient and performing a physical examination. Several types of brain imaging, including computer histomography, scans, magnetic resonance imaging (MRI), and positron emission tomography (PET), are used. Pharmacological challenge tests (administering certain drugs in the presence of various types of movement of the patient) may also be of help in those patients with typical Parkinsonism signs. An incomplete and relatively poor response to dopamine replacement therapy, such as Sinemet, may be a clue that MSA is present. A characteristic involvement of multiple brain systems is a defining feature of MSA and one that an autopsy confirms the diagnosis. Patients with MSA can have the presence of glial cytoplasmic inclusions in certain types of brain cells, as well. Lewy bodies are not present in MSA. In comparison to Parkinson's, in addition to the poor response to Sinemet, there are a few other observations that are suggested for MSA, such as low blood pressure on standing, difficulty with urination, use of a wheelchair, loud snoring or loud breathing, and frequent nighttime urination.

Methods of the invention can be used in combination with one or more alternative medications for treating MSA. Typically, the drugs that can be used to treat various symptoms of MSA become less effective as the disease progresses. Levodopa and dopamine agonists used to treat PD are sometimes effective for the slowness and rigidity of MSA. Orthostatic hypertension can be improved with cortisone, midodrine, or other drugs that raise blood pressure. Male impotence may be treated with penile implants or drugs. Incontinence may be treated with medication or catheterization. Constipation may improve with increased dietary fiber or laxatives.

According to the invention, the term "treatment" includes prophylaxis and therapy, and includes managing a synucleinopathic subject's symptoms and halting the progression of the

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synucleinopathy. Treatment includes preventing, slowing, stopping, or reversing curing) the development of a synucleinopathy, and/or the onset of certain symptoms associated with a O synucleinopathy in a subject with, or at risk of developing, a synucleinopathy or a related 00 disorder. Therapy includes preventing, slowing, stopping or reversing curing) the accumulation of a-synuclein in a subject with a synucleinopathy. Therapy also includes decreasing the amount of accumulated a-synuclein in a subject with a synucleinopathy.

\The phrase "therapeutically-effective amount" as used herein means that amount of a compound, material, or composition comprising a compound of the present invention which is s0 effective for producing some desired therapeutic effect in a subject at a reasonable benefit/risk 0 10 ratio applicable to any medical treatment. Accordingly, a therapeutically effective amount prevents, minimizes, or reverses disease progression associated with a synucleinopathy..

Disease progression can be monitored by clinical observations, laboratory and neuroimaging investigations apparent to a person skilled in the art. A therapeutically effective amount can be an amount that is effective in a single dose or an amount that is effective as part of a multi-dose therapy, for example an amount that is administered in two or more doses or an amount that is administered chronically.

The "pharmaceutically acceptable acid or base addition salts" mentioned herein are meant to comprise the therapeutically active non-toxic acid and non-toxic base addition salt forms that the compounds are able to form. The compounds that have basic properties can be converted into their pharmaceutically acceptable acid addition salts by treating the base form with an appropriate acid. Appropriate acids include, for example, inorganic acids such as hydrohalic acids, e.g. hydrochloric or hydrobromic acid; sulfuric; nitric; phosphoric and the like acids; or organic acids such as, for example, acetic, propanoic, hydroxyacetic, lactic, pyruvic, oxalic, malonic, succinic butanedioic acid), maleic, fumaric, malic, tartaric, citric, methanesulfonic, ethanesulfonic, benzenesulfonic, p-toluenesulfonic, cyclamic, salicylic, paminosalicylic, pamoic and the like acids.

The compounds that have acidic properties can be converted into their pharmaceutically acceptable base addition salts by treating the acid form with a suitable organic or inorganic base. Appropriate base salt forms include, for example, the ammonium salts, the alkali and earth alkaline metal salts, e.g. the lithium, sodium, potassium, magnesium, calcium salts and the like, salts with organic bases, e.g. the benzathine, N-methyl-D-glucamine, hydrabamine salts, and salts with amino acids such as, for example, arginine, lysine and the like.

The terms acid or base addition salt also comprise the hydrates and the solvent addition forms which the compounds are able to form. Examples of such forms are e.g. hydrates, 206

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alcoholates and the like.

04 The term stereochemically isomeric forms of compounds, as used herein, include all O possible compounds made up of the same atoms bonded by the same sequence of bonds but oO having different three-dimensional structures which are not interchangeable, which the compounds may possess. Unless otherwise mentioned or indicated, the chemical designation of a compound encompasses the mixture of all possible stereochemically isomeric forms that the compound can take. The mixture can contain all diastereomers and/or enantiomers of the basic c molecular structure of the compound. All stereochemically isomeric forms of the compounds ,O both in pure form or in admixture with each other are intended to be embraced within the scope

O

0 10 of the present invention.

Some of the compounds may also exist in their tautomeric forms. Such forms although not explicitly indicated in the above formula are intended to be included within the scope of the present invention.

The methods and structures described herein relating to compounds and compositions of the invention also apply to the pharmaceutically acceptable acid or base addition salts and all stereoisomeric forms of these compounds and compositions.

In the compounds and compositions of the invention, the term "alkyl" refers to the radical of saturated aliphatic groups, including straight-chain alkyl groups, branched-chain alkyl groups, cycloalkyl (alicyclic) groups, alkyl substituted cycloalkyl groups, and cycloalkyl !0 substituted alkyl groups. In preferred embodiments, a straight chain or branched chain alkyl has 12 or fewer carbon atoms in its backbone C 1

-C

2 for straight chain, C 3

-CI

2 for branched chain), and more preferably 6 or fewer, and even more preferably 4 or fewer.

Likewise, preferred cycloalkyls have from 3-10 carbon atoms in their ring structure, and more preferably have 5, 6 or 7 carbons in the ring structure.

Unless the number of carbons is otherwise specified, "lower alkyl" as used herein means an alkyl group, as defined above, but having from one to ten carbons, more preferably from one to six carbon atoms in its backbone structure, and even more preferably from one to four carbon atoms in its backbone structure. Likewise, "lower alkenyl" and "lower alkynyl" have similar chain lengths. Preferred alkyl groups are lower alkyls. In preferred embodiments, a substituent designated herein as alkyl is a lower alkyl.

As used herein, the term "halogen" designates -Cl, -Br or the term "sulfhydryl" means -SH; and the term "hydroxyl" means -OH.

The term "methyl" refers to the monovalent radical -CH 3 and the term "methoxyl" refers to the monovalent radical 207

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The term "aralkyl" or "arylalkyl", as used herein, refers to an alkyl group substituted with an aryl group an aromatic or heteroaromatic group).

O The terms "alkenyl" and "alkynyl" refer to unsaturated aliphatic groups analogous in 0O length and possible substitution to the alkyls described above, but that contain at least one double or triple bond respectively.

The term "aryl" as used herein includes 6- and 7-membered single-ring aromatic l groups that may include from zero to four heteroatoms, for example, benzene, pyrrole, furan, c thiophene, imidazole, oxazole, thiazole, triazole, pyrazole, pyridine, pyrazine, pyridazine and ND pyrimidine, and the like. Those aryl groups having heteroatoms in the ring structure may also 0 10 be referred to as "aryl heterocycles" or "heteroaromatics." The aromatic ring can be substituted at one or more ring positions with such substituents as described above, for example, halogen, azide, alkyl, aralkyl, alkenyl, alkynyl, cycloalkyl, hydroxyl, alkoxyl, amino, nitro, sulfhydryl, imino, amido, phosphonate, phosphinate, carbonyl, carboxyl, silyl, ether, alkylthio, sulfonyl, sulfonamido, ketone, aldehyde, ester, heterocyclyl, aromatic or heteroaromatic moieties, -CF 3 CN, or the like. The term "aryl" also includes polycyclic ring systems having two or more cyclic rings in which two or more carbons are common to two adjoining rings (the rings are "fused rings") wherein at least one of the rings is aromatic, the other cyclic rings can be cycloalkyls, cycloalkenyls, cycloalkynyls, aryls and/or heterocyclyls.

The terms "ortho", "meta" and "para" apply to 1,3- and 1,4-disubstituted benzenes, respectively. For example, the names 1,2-dimethylbenzene and ortho-dimethylbenzene are synonymous.

The terms "heterocyclyl" or "heterocyclic group" or "heteroaryl" refer to 3- to membered ring structures, more preferably 3- to 7-membered rings, whose ring structures include one to four heteroatoms. Heterocycles can also be polycycles. Heterocyclyl groups include, for example, thiophene, benzothiophene, thianthrene, furan, pyran, isobenzofuran, chromene, xanthene, phenoxathiin, pyrrole, imidazole, pyrazole, isothiazole, isoxazole, pyridine, pyrazine, pyrimidine, pyridazine, indolizine, isoindole, indole, indazole, purine, quinolizine, isoquinoline, quinoline, phthalazine, naphthyridine, quinoxaline, quinazoline, cinnoline, pteridine, carbazole, carboline, phenanthridine, acridine, pyrimidine, phenanthroline, phenazine, phenarsazine, phenothiazine, furazan, phenoxazine, pyrrolidine, oxolane, thiolane, oxazole, piperidine, piperazine, morpholine, lactones, lactams such as azetidinones and pyrrolidinones, sultams, sultones, and the like. The heterocyclic ring can be substituted at one or more positions with such substituents as described above, as for example, halogen, alkyl, aralkyl, alkenyl, alkynyl, cycloalkyl, hydroxyl, amino, nitro, sulfhydryl, imino, amido,

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phosphonate, phosphinate, carbonyl, carboxyl, silyl, ether, alkylthio, sulfonyl, ketone, aldehyde, S ester, a heterocyclyl, an aromatic or heteroaromatic moiety, -CF 3 -CN, or the like.

jO As used herein, the definition of each expression, e.g. alkyl, m, n, etc., when it occurs 00 more than once in any structure, is intended to be independent of its definition elsewhere in the same structure.

It will be understood that "substitution" or "substituted with" includes the implicit 0 proviso that such substitution is in accordance with permitted valence of the substituted atom c and the substituent, and that the substitution results in a stable compound, which does not spontaneously undergo transformation such as by rearrangement, cyclization, elimination, etc.

0 10 As used herein, the term "substituted" is contemplated to include all permissible substituents of organic compounds. In a broad aspect, the permissible substituents include acyclic and cyclic, branched and unbranched, carbocyclic and heterocyclic, aromatic and nonaromatic substituents of organic compounds. Illustrative substituents include, for example, those described herein above. The permissible substituents can be one or more and the same or different for appropriate organic compounds. For purposes of this invention, the heteroatoms such as nitrogen may have hydrogen substituents and/or any permissible substituents of organic compounds described herein which satisfy the valences of the heteroatoms. This invention is not intended to be limited in any manner by the permissible substituents of organic compounds.

Certain compounds of the present invention may exist in particular geometric or stereoisomeric forms. The present invention contemplates all such compounds, including cisand trans-isomers, R- and S-enantiomers, diastereomers, (D)-isomers, (L)-isomers, the racemic mixtures thereof, and other mixtures thereof, as falling within the scope of the invention.

Additional asymmetric carbon atoms may be present in a substituent such as an alkyl group.

All such isomers, as well as mixtures thereof, are intended to be included in this invention. In certain embodiments, the present invention relates to a compound represented by any of the structures outlined herein, wherein the compound is a single stereoisomer.

If, for instance, a particular enantiomer of a compound of the present invention is desired, it may be prepared by asymmetric synthesis, or by derivation with a chiral auxiliary, where the resulting diastereomeric mixture is separated and the auxiliary group cleaved to provide the pure desired enantiomers. Alternatively, where the molecule contains a basic functional group, such as amino, or an acidic functional group, such as carboxyl, diastereomeric salts are formed with an appropriate optically-active acid or base, followed by resolution of the diastereomers thus formed by fractional crystallization or chromatographic means well known in the art, and subsequent recovery of the pure enantiomers.

O Contemplated equivalents of the compounds described above include compounds which otherwise correspond thereto, and which have the same general properties thereof S functioning as anti-synucleinopathy farnesyl transferase inhibitor compounds), wherein one or oO more simple variations of substituents are made which do not adversely affect the efficacy of the compound. In general, the compounds of the present invention may be prepared by the methods illustrated in the general reaction schemes as, for example, described below, or by Smodifications thereof, using readily available starting materials, reagents and conventional Cc synthesis procedures. In these reactions, it is also possible to make use of variants, which are in ID themselves known, but are not mentioned here.

C 10 For purposes of this invention, the chemical elements are identified in accordance with the Periodic Table of the Elements, CAS version, Handbook of Chemistry and Physics, 67th Ed., 1986-87, inside cover.

In another aspect, the present invention provides "pharmaceutically acceptable" compositions, which comprise a therapeutically effective amount of one or more of the compounds described herein, formulated together with one or more pharmaceutically acceptable carriers (additives) and/or diluents. As described in detail, the pharmaceutical compositions of the present invention may be specially formulated for administration in solid or liquid form, including those adapted for the following: oral administration, for example, drenches (aqueous or non-aqueous solutions or suspensions), tablets, those targeted for buccal, sublingual, and systemic absorption, boluses, powders, granules, pastes for application to the tongue; parenteral administration, for example, by subcutaneous, intramuscular, intravenous or epidural injection as, for example, a sterile solution or suspension, or sustainedrelease formulation; topical application, for example, as a cream, ointment, or a controlledrelease patch or spray applied to the skin, lungs, or oral cavity; intravaginally or intrarectally, for example, as a pessary, cream or foam; sublingually; ocularly; transdermally; or nasally, pulmonary and to other mucosal surfaces.

The phrase "pharmaceutically acceptable" is employed herein to refer to those compounds, materials, compositions, and/or dosage forms which are, within the scope of sound medical judgment, suitable for use in contact with the tissues of human beings and animals without excessive toxicity, irritation, allergic response, or other problem or complication, commensurate with a reasonable benefit/risk ratio.

The phrase "pharmaceutically-acceptable carrier" as used herein means a pharmaceutically-acceptable material, composition or vehicle, such as a liquid or solid filler, diluent, excipient, or solvent encapsulating material, involved in carrying or transporting the

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O subject compound from one organ, or portion of the body, to another organ, or portion of the S body. Each carrier must be "acceptable" in the sense of being compatible with the other Singredients of the formulation and not injurious to the patient. Some examples of materials 00 which can serve as pharmaceutically-acceptable carriers include: sugars, such as lactose, glucose and sucrose; starches, such as corn starch and potato starch; cellulose, and its derivatives, such as sodium carboxymethyl cellulose, ethyl cellulose and cellulose acetate; Spowdered tragacanth; malt; gelatin; talc; excipients, such as cocoa butter and suppository waxes; oils, such as peanut oil, cottonseed oil, safflower oil, sesame oil, olive oil, corn oil and IO soybean oil; glycols, such as propylene glycol; polyols, such as glycerin, sorbitol, mannitol and 0 C 10 polyethylene glycol; esters, such as ethyl oleate and ethyl laurate; agar; buffering agents, such as magnesium hydroxide and aluminum hydroxide; alginic acid; pyrogen-free water; isotonic saline; Ringer's solution; ethyl alcohol; pH buffered solutions; polyesters, polycarbonates and/or polyanhydrides; and other non-toxic compatible substances employed in pharmaceutical formulations.

As set out herein, certain embodiments of the present compounds may contain a basic functional group, such as amino or alkylamino, and are, thus, capable of forming pharmaceutically-acceptable salts with pharmaceutically-acceptable acids. The term "pharmaceutically-acceptable salts" in this respect refers to the relatively non-toxic, inorganic and organic acid addition salts of compounds of the present invention. These salts can be prepared in situ in the administration vehicle or the dosage form manufacturing process, or by separately reacting a purified compound of the invention in its free base form with a suitable organic or inorganic acid, and isolating the salt thus formed during subsequent purification.

Representative salts include the hydrobromide, hydrochloride, sulfate, bisulfate, phosphate, nitrate, acetate, valerate, oleate, palmitate, stearate, laurate, benzoate, lactate, phosphate, tosylate, citrate, maleate, fumarate, succinate, tartrate, napthylate, mesylate, glucoheptonate, lactobionate, and laurylsulphonate salts and the like. (See, for example, Berge et al. (1977) "Pharmaceutical Salts", J. Pharm. Sci. 66:1-19) The pharmaceutically acceptable salts of the subject compounds include the conventional nontoxic salts or quaternary ammonium salts of the compounds, from nontoxic organic or inorganic acids. For example, such conventional nontoxic salts include those derived from inorganic acids such as hydrochloride, hydrobromic, sulfuric, sulfamic, phosphoric, nitric, and the like; and the salts prepared from organic acids such as acetic, propionic, succinic, glycolic, stearic, lactic, malic, tartaric, citric, ascorbic, palmitic, maleic, hydroxymaleic, phenylacetic, glutamic, benzoic, salicyclic, sulfanilic, 2-acetoxybenzoic,

ID

fumaric, toluenesulfonic, methanesulfonic, ethane disulfonic, oxalic, isothionic, and the like.

In other cases, the compounds of the present invention may contain one or more acidic Sfunctional groups and, thus, are capable of forming pharmaceutically-acceptable salts with 00 pharmaceutically-acceptable bases. The term "pharmaceutically-acceptable salts" in these instances refers to the relatively non-toxic, inorganic and organic base addition salts of compounds of the present invention. These salts can likewise be prepared in situ in the t administration vehicle or the dosage form manufacturing process, or by separately reacting the c purified compound in its free acid form with a suitable base, such as the hydroxide, carbonate or bicarbonate of a pharmaceutically-acceptable metal cation, with ammonia, or with a 0 10 pharmaceutically-acceptable organic primary, secondary or tertiary amine. Representative alkali or alkaline earth salts include the lithium, sodium, potassium, calcium, magnesium, and aluminum salts and the like. Representative organic amines useful for the formation of base addition salts include ethylamine, diethylamine, ethylenediamine, ethanolamine, diethanolamine, piperazine and the like. (See, for example, Berge et al., supra).

Wetting agents, emulsifiers and lubricants, such as sodium lauryl sulfate and magnesium stearate, as well as coloring agents, release agents, coating agents, sweetening, flavoring and perfuming agents, preservatives and antioxidants can also be present in the compositions.

Examples of pharmaceutically-acceptable antioxidants include: water soluble antioxidants, such as ascorbic acid, cysteine hydrochloride, sodium bisulfate, sodium metabisulfite, sodium sulfite and the like; oil-soluble antioxidants, such as ascorbyl palmitate, butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), lecithin, propyl gallate, alpha-tocopherol, and the like; and metal chelating agents, such as citric acid, ethylenediamine tetraacetic acid (EDTA), sorbitol, tartaric acid, phosphoric acid, and the like.

Formulations of the present invention include those suitable for oral, nasal, topical (including buccal and sublingual), rectal, vaginal and/or parenteral administration. The formulations may conveniently be presented in unit dosage form and may be prepared by any methods well known in the art of pharmacy. The amount of active ingredient which can be combined with a carrier material to produce a single dosage form will vary depending upon the host being treated, and the particular mode of administration. The amount of active ingredient that can be combined with a carrier material to produce a single dosage form will generally be that amount of the compound which produces a therapeutic effect. Generally, this amount will range from about 1% to about 99% of active ingredient, preferably from about 5% to about most preferably from about 10% to about O In certain embodiments, a formulation of the present invention comprises an excipient selected from the group consisting ofcyclodextrins, liposomes, micelle forming agents, e.g., S bile acids, and polymeric carriers, polyesters and polyanhydrides; and a compound of the oO present invention. In certain embodiments, an aforementioned formulation renders orally bioavailable a compound of the present invention.

Methods of preparing these formulations or compositions include the step of bringing into association a compound of the present invention with the carrier and, optionally, one or Smore accessory ingredients. In general, the formulations are prepared by uniformly and INO intimately bringing into association a compound of the present invention with liquid carriers, or C 10 finely divided solid carriers, or both, and then, if necessary, shaping the product.

Formulations of the invention suitable for oral administration may be in the form of capsules, cachets, pills, tablets, lozenges (using a flavored basis, usually sucrose and acacia or tragacanth), powders, granules, or as a solution or a suspension in an aqueous or non-aqueous liquid, or as an oil-in-water or water-in-oil liquid emulsion, or as an elixir or syrup, or as pastilles (using an inert base, such as gelatin and glycerin, or sucrose and acacia) and/or as mouth washes and the like, each containing a predetermined amount of a compound of the present invention as an active ingredient. A compound of the present invention may also be administered as a bolus, electuary or paste.

In solid dosage forms of the invention for oral administration (capsules, tablets, pills, dragees, powders, granules and the like), the active ingredient is mixed with one or more pharmaceutically-acceptable carriers, such as sodium citrate or dicalcium phosphate, and/or any of the following: fillers or extenders, such as starches, lactose, sucrose, glucose, mannitol, and/or silicic acid; binders, such as, for example, carboxymethylcellulose, alginates, gelatin, polyvinyl pyrrolidone, sucrose and/or acacia; humectants, such as glycerol; disintegrating agents, such as agar-agar, calcium carbonate, potato or tapioca starch, alginic acid, certain silicates, and sodium carbonate; solution retarding agents, such as paraffin; absorption accelerators, such as quaternary ammonium compounds; wetting agents, such as, for example, cetyl alcohol, glycerol monostearate, and non-ionic surfactants; absorbents, such as kaolin and bentonite clay; lubricants, such as talc, calcium stearate, magnesium stearate, solid polyethylene glycols, sodium lauryl sulfate, and mixtures thereof; and coloring agents. In the case of capsules, tablets and pills, the pharmaceutical compositions may also comprise buffering agents. Solid compositions of a similar type may also be employed as fillers in soft and hardshelled gelatin capsules using such excipients as lactose or milk sugars, as well as high molecular weight polyethylene glycols and the like.

o A tablet may be made by compression or molding, optionally with one or more accessory ingredients. Compressed tablets may be prepared using binder (for example, gelatin o or hydroxypropylmethyl cellulose), lubricant, inert diluent, preservative, disintegrant (for 00 example, sodium starch glycolate or cross-linked sodium carboxymethyl cellulose), surfaceactive or dispersing agent. Molded tablets may be made in a suitable machine in which a mixture of the powdered compound is moistened with an inert liquid diluent.

The tablets, and other solid dosage forms of the pharmaceutical compositions of the Cc present invention, such as dragees, capsules, pills and granules, may optionally be scored or prepared with coatings and shells, such as enteric coatings and other coatings well known in the C 10 pharmaceutical-formulating art. They may also be formulated so as to provide slow or controlled release of the active ingredient therein using, for example, hydroxypropylmethyl cellulose in varying proportions to provide the desired release profile, other polymer matrices, liposomes and/or microspheres. They may be formulated for rapid release, freeze-dried.

They may be sterilized by, for example, filtration through a bacteria-retaining filter, or by incorporating sterilizing agents in the form of sterile solid compositions that can be dissolved in sterile water, or some other sterile injectable medium immediately before use. These compositions may also optionally contain opacifying agents and may be of a composition that they release the active ingredient(s) only, or preferentially, in a certain portion of the gastrointestinal tract, optionally, in a delayed manner. Examples of embedding compositions that can be used include polymeric substances and waxes. The active ingredient can also be in micro-encapsulated form, if appropriate, with one or more of the above-described excipients.

Liquid dosage forms for oral administration of the compounds of the invention include pharmaceutically acceptable emulsions, microemulsions, solutions, suspensions, syrups and elixirs. In addition to the active ingredient, the liquid dosage forms may contain inert diluents commonly used in the art, such as, for example, water or other solvents, solubilizing agents and emulsifiers, such as ethyl alcohol, isopropyl alcohol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1,3-butylene glycol, oils (in particular, cottonseed, groundnut, corn, germ, olive, castor and sesame oils), glycerol, tetrahydrofuryl alcohol, polyethylene glycols and fatty acid esters of sorbitan, and mixtures thereof.

Besides inert diluents, the oral compositions can also include adjuvants such as wetting agents, emulsifying and suspending agents, sweetening, flavoring, coloring, perfuming and preservative agents.

Suspensions, in addition to the active compounds, may contain suspending agents as, for example, ethoxylated isostearyl alcohols, polyoxyethylene sorbitol and sorbitan esters, 214 O microcrystalline cellulose, aluminum metahydroxide, bentonite, agar-agar and tragacanth, and mixtures thereof.

o Formulations of the pharmaceutical compositions of the invention for rectal or vaginal oO administration may be presented as a suppository, which may be prepared by mixing one or more compounds of the invention with one or more suitable nonirritating excipients or carriers comprising, for example, cocoa butter, polyethylene glycol, a suppository wax or a salicylate, O and which is solid at room temperature, but liquid at body temperature and, therefore, will melt Cc in the rectum or vaginal cavity and release the active compound.

IDFormulations of the present invention which are suitable for vaginal administration also include pessaries, tampons, creams, gels, pastes, foams or spray formulations containing such carriers as are known in the art to be appropriate.

Dosage forms for the topical or transdermal administration of a compound of this invention include powders, sprays, ointments, pastes, creams, lotions, gels, solutions, patches and inhalants. The active compound may be mixed under sterile conditions with a pharmaceutically-acceptable carrier, and with any preservatives, buffers, or propellants which may be required.

The ointments, pastes, creams and gels may contain, in addition to an active compound of this invention, excipients, such as animal and vegetable fats, oils, waxes, paraffins, starch, tragacanth, cellulose derivatives, polyethylene glycols, silicones, bentonites, silicic acid, talc and zinc oxide, or mixtures thereof.

Powders and sprays can contain, in addition to a compound of this invention, excipients such as lactose, talc, silicic acid, aluminum hydroxide, calcium silicates and polyamide powder, or mixtures of these substances. Sprays can additionally contain customary propellants, such as chlorofluorohydrocarbons and volatile unsubstituted hydrocarbons, such as butane and propane.

Transdermal patches have the added advantage of providing controlled delivery of a compound of the present invention to the body. Dissolving or dispersing the compound in the proper medium can make such dosage forms. Absorption enhancers can also be used to increase the flux of the compound across the skin. Either providing a rate controlling membrane or dispersing the compound in a polymer matrix or gel can control the rate of such flux.

Ophthalmic formulations, eye ointments, powders, solutions and the like, are also contemplated as being within the scope of this invention.

Pharmaceutical compositions of this invention suitable for parenteral administration comprise one or more compounds of the invention in combination with one or more

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pharmaceutically-acceptable sterile isotonic aqueous or nonaqueous solutions, dispersions, suspensions or emulsions, or sterile powders which may be reconstituted into sterile injectable

C.)

O solutions or dispersions just prior to use, which may contain sugars, alcohols, antioxidants, 00 buffers, bacteriostats, solutes which render the formulation isotonic with the blood of the intended recipient or suspending or thickening agents.

Examples of suitable aqueous and nonaqueous carriers, which may be employed in the O pharmaceutical compositions of the invention include water, ethanol, polyols (such as glycerol, propylene glycol, polyethylene glycol, and the like), and suitable mixtures thereof, vegetable IO oils, such as olive oil, and injectable organic esters, such as ethyl oleate. Proper fluidity can be 0 C 10 maintained, for example, by the use of coating materials, such as lecithin, by the maintenance of the required particle size in the case of dispersions, and by the use of surfactants.

These compositions may also contain adjuvants such as preservatives, wetting agents, emulsifying agents and dispersing agents. Prevention of the action of microorganisms upon the subject compounds may be ensured by the inclusion of various antibacterial and antifungal agents, for example, paraben, chlorobutanol, phenol sorbic acid, and the like. It may also be desirable to include isotonic agents, such as sugars, sodium chloride, and the like into the compositions. In addition, prolonged absorption of the injectable pharmaceutical form may be brought about by the inclusion of agents which delay absorption such as aluminum monostearate and gelatin.

In some cases, in order to prolong the effect of a drug, it is desirable to slow the absorption of the drug from subcutaneous or intramuscular injection. This may be accomplished by the use of a liquid suspension of crystalline or amorphous material having poor water solubility. The rate of absorption of the drug then depends upon its rate of dissolution, which in turn, may depend upon crystal size and crystalline form.

Alternatively, delayed absorption of a parenterally-administered drug form is accomplished by dissolving or suspending the drug in an oil vehicle.

Injectable depot forms are made by forming microencapsule matrices of the subject compounds in biodegradable polymers such as polylactide-polyglycolide. Depending on the ratio of drug to polymer, and the nature of the particular polymer employed, the rate of drug release can be controlled. Examples of other biodegradable polymers include poly(orthoesters) and poly(anhydrides). Depot injectable formulations are also prepared by entrapping the drug in liposomes or microemulsions, which are compatible with body tissue.

In certain embodiments, a compound or pharmaceutical preparation is administered orally. In other embodiments, the compound or pharmaceutical preparation is administered 216

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O intravenously. Alternative routs of administration include sublingual, intramuscular, and transdermal administrations.

O When the compounds of the present invention are administered as pharmaceuticals, to 00 humans and animals, they can be given per se or as a pharmaceutical composition containing, for example, 0.1% to 99.5% (more preferably, 0.5% to 90%) of active ingredient in combination with a pharmaceutically acceptable carrier.

The preparations of the present invention may be given orally, parenterally, topically, or rectally. They are of course given in forms suitable for each administration route. For example, I they are administered in tablets or capsule form, by injection, inhalation, eye lotion, ointment, 0 10 suppository, etc. administration by injection, infusion or inhalation; topical by lotion or ointment; and rectal by suppositories. Oral administrations are preferred.

The phrases "parenteral administration" and "administered parenterally" as used herein means modes of administration other than enteral and topical administration, usually by injection, and includes, without limitation, intravenous, intramuscular, intraarterial, intrathecal, intracapsular, intraorbital, intracardiac, intradermal, intraperitoneal, transtracheal, subcutaneous, subcuticular, intraarticulare, subcapsular, subarachnoid, intraspinal and intrasternal injection and infusion.

The phrases "systemic administration," "administered systemically," "peripheral Sadministration" and "administered peripherally" as used herein mean the administration of a compound, drug or other material other than directly into the central nervous system, such that it enters the patient's system and, thus, is subject to metabolism and other like processes, for example, subcutaneous administration.

These compounds may be administered to humans and other animals for therapy by any suitable route of administration, including orally, nasally, as by, for example, a spray, rectally, intravaginally, parenterally, intracisternally and topically, as by powders, ointments or drops, including buccally and sublingually.

Regardless of the route of administration selected, the compounds of the present invention, which may be used in a suitable hydrated form, and/or the pharmaceutical compositions of the present invention, are formulated into pharmaceutically-acceptable dosage forms by conventional methods known to those of skill in the art.

Actual dosage levels of the active ingredients in the pharmaceutical compositions of this invention may be varied so as to obtain an amount of the active ingredient that is effective to achieve the desired therapeutic response for a particular patient, composition, and mode of administration, without being toxic to the patient.

217 The selected dosage level will depend upon a variety of factors including the activity of the particular compound of the present invention employed, or the ester, salt or amide thereof, Sthe route of administration, the time of administration, the rate of excretion or metabolism of OO the particular compound being employed, the duration of the treatment, other drugs, compounds and/or materials used in combination with the particular compound employed, the age, sex, weight, condition, general health and prior medical history of the patient being treated, and like factors well known in the medical arts.

A physician or veterinarian having ordinary skill in the art can readily determine and IND prescribe the effective amount of the pharmaceutical composition required. For example, the C 10 physician or veterinarian could start doses of the compounds of the invention employed in the pharmaceutical composition at levels lower than that required to achieve the desired therapeutic effect and then gradually increasing the dosage until the desired effect is achieved.

In some embodiments, a compound or pharmaceutical composition of the invention is provided to a synucleinopathic subject chronically. Chronic treatments include any form of repeated administration for an extended period of time, such as repeated administrations for one or more months, between a month and a year, one or more years, or longer. In many embodiments, a chronic treatment involves administering a compound or pharmaceutical composition of the invention repeatedly over the life of the synucleinopathic subject. Preferred chronic treatments involve regular administrations, for example one or more times a day, one or more times a week, or one or more times a month. In general, a suitable dose such as a daily dose of a compound of the invention will be that amount of the compound that is the lowest dose effective to produce a therapeutic effect. Such an effective dose will generally depend upon the factors described above. Generally doses of the compounds of this invention for a patient, when used for the indicated effects, will range from about 0.0001 to about 100 mg per kg of body weight per day. Preferably the daily dosage will range from 0.001 to 50 mg of compound per kg of body weight, and even more preferably from 0.01 to 10 mg of compound per kg of body weight. However, lower or higher doses can be used. In some embodiments, the dose administered to a subject may be modified as the physiology of the subject changes due to age, disease progression, weight, or other factors.

If desired, the effective daily dose of the active compound may be administered as two, three, four, five, six or more sub-doses administered separately at appropriate intervals throughout the day, optionally, in unit dosage forms.

While it is possible for a compound of the present invention to be administered alone, it is preferable to administer the compound as a pharmaceutical formulation (composition) as

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described above.

The compounds according to the invention may be formulated for administration in any o convenient way for use in human or veterinary medicine, by analogy with other 00 pharmaceuticals.

According to the invention, compounds for treating neurological conditions or diseases can be formulated or administered using methods that help the compounds cross the blood- Sbrain barrier (BBB). The vertebrate brain [and CNS] has a unique capillary system unlike that Cc in any other organ in the body. The unique capillary system has morphologic characteristics 11which make up the blood-brain barrier (BBB). The blood-brain barrier acts as a system-wide cellular membrane that separates the brain interstitial space from the blood.

The unique morphologic characteristics of the brain capillaries that make up the BBB are: epithelial-like high resistance tight junctions which literally cement all endothelia of brain capillaries together, and scanty pinocytosis or transendothelial channels, which are abundant in endothelia of peripheral organs. Due to the unique characteristics of the bloodbrain barrier, hydrophilic drugs and peptides that readily gain access to other tissues in the body are barred from entry into the brain or their rates of entry and/or accumulation in the brain are very low.

In one aspect of the invention, famrnesyl transferase inhibitor compounds that cross the BBB are particularly useful for treating synucleinopathies. In one embodiment, it is expected that famesyl transferase inhibitors that are non-charged not positively charged) and/or non-lipophilic may cross the BBB with higher efficiency than charged positively charged) and/or lipophilic compounds. Therefore it will be appreciated by a person of ordinary skill in the art that some of the compounds of the invention might readily cross the BBB.

Alternatively, the compounds of the invention can be modified, for example, by the addition of various substitutuents that would make them less hydrophilic and allow them to more readily cross the BBB.

Various strategies have been developed for introducing those drugs into the brain which otherwise would not cross the blood-brain barrier. Widely used strategies involve invasive procedures where the drug is delivered directly into the brain. One such procedure is the implantation of a catheter into the ventricular system to bypass the blood-brain barrier and deliver the drug directly to the brain. These procedures have been used in the treatment of brain diseases which have a predilection for the meninges, leukemic involvement of the brain (US 4,902,505, incorporated herein in its entirety by reference).

Although invasive procedures for the direct delivery of drugs to the brain ventricles

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have experienced some success, they are limited in that they may only distribute the drug to S superficial areas of the brain tissues, and not to the structures deep within the brain. Further, O the invasive procedures are potentially harmful to the patient.

00 Other approaches to circumventing the blood-brain barrier utilize pharmacologic-based procedures involving drug latentiation or the conversion of hydrophilic drugs into lipid-soluble drugs. The majority of the latentiation approaches involve blocking the hydroxyl, carboxyl and \primary amine groups on the drug to make it more lipid-soluble and therefore more easily able c to cross the blood-brain barrier.

Another approach to increasing the permeability of the BBB to drugs involves the intra- 0 10 arterial infusion of hypertonic substances which transiently open the blood-brain barrier to allow passage of hydrophilic drugs. However, hypertonic substances are potentially toxic and may damage the blood-brain barrier.

Peptide compositions of the invention may be administered using chimeric peptides wherein the hydrophilic peptide drug is conjugated to a transportable peptide, capable of crossing the blood-brain barrier by transcytosis at a much higher rate than the hydrophilic peptides alone. Suitable transportable peptides include, but are not limited to, histone, insulin, transferrin, insulin-like growth factor I (IGF-I), insulin-like growth factor II (IGF-II), basic albumin and prolactin.

Antibodies are another method for delivery of compositions of the invention. For example, an antibody that is reactive with a transferrin receptor present on a brain capillary endothelial cell, can be conjugated to a neuropharmaceutical agent to produce an antibodyneuropharmaceutical agent conjugate (US 5,004,697 incorporated herein in its entirety by reference). The method is conducted under conditions whereby the antibody binds to the transferrin receptor on the brain capillary endothelial cell and the neuropharmaceutical agent is transferred across the blood brain barrier in a pharmaceutically active form. The uptake or transport of antibodies into the brain can also be greatly increased by cationizing the antibodies to form cationized antibodies having an isoelectric point of between about 8.0 to 11.0 (US 5,527,527 incorporated herein in its entirety by reference).

A ligand-neuropharmaceutical agent fusion protein is another method useful for delivery of compositions to a host (US 5,977,307, incorporated herein in its entirety by reference). The ligand is reactive with a brain capillary endothelial cell receptor. The method is conducted under conditions whereby the ligand binds to the receptor on a brain capillary endothelial cell and the neuropharmaceutical agent is transferred across the blood brain barrier in a pharmaceutically active form. In some embodiments, a ligand-neuropharmaceutical agent 220

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O fusion protein, which has both ligand binding and neuropharmaceutical characteristics, can be S produced as a contiguous protein by using genetic engineering techniques. Gene constructs can S be prepared comprising DNA encoding the ligand fused to DNA encoding the protein, 00 polypeptide or peptide to be delivered across the blood brain barrier. The ligand coding sequence and the agent coding sequence are inserted in the expression vectors in a suitable manner for proper expression of the desired fusion protein. The gene fusion is expressed as a contiguous protein molecule containing both a ligand portion and a neuropharmaceutical agent Cc portion.

IND The permeability of the blood brain barrier can be increased by administering a blood brain barrier agonist, for example bradykinin (US 5,112,596 incorporated herein in its entirety by reference), or polypeptides called receptor mediated permeabilizers (RMP) (US 5,268,164 incorporated herein in its entirety by reference). Exogenous molecules can be administered to the host's bloodstream parenterally by subcutaneous, intravenous or intramuscular injection or by absorption through a bodily tissue, such as the digestive tract, the respiratory system or the skin. The form in which the molecule is administered capsule, tablet, solution, emulsion) depends, at least in part, on the route by which it is administered. The administration of the exogenous molecule to the host's bloodstream and the intravenous injection of the agonist of blood-brain barrier permeability can occur simultaneously or sequentially in time. For example, a therapeutic drug can be administered orally in tablet form while the intravenous administration of an agonist of blood-brain barrier permeability is given later between minutes later and several hours later). This allows time for the drug to be absorbed in the gastrointestinal tract and taken up by the bloodstream before the agonist is given to increase the permeability of the blood-brain barrier to the drug. On the other hand, an agonist of bloodbrain barrier permeability bradykinin) can be administered before or at the same time as an intravenous injection of a drug. Thus, the term "co administration" is used herein to mean that the agonist of blood-brain barrier and the exogenous molecule will be administered at times that will achieve significant concentrations in the blood for producing the simultaneous effects of increasing the permeability of the blood-brain barrier and allowing the maximum passage of the exogenous molecule from the blood to the cells of the central nervous system.

In other embodiments, compounds of the invention can be formulated as a prodrug with a fatty acid carrier (and optionally with another neuroactive drug). The prodrug is stable in the environment of both the stomach and the bloodstream and may be delivered by ingestion. The prodrug passes readily through the blood brain barrier. The prodrug preferably has a brain penetration index of at least two times the brain penetration index of the drug alone. Once in the central nervous system, the prodrug, which preferably is inactive, is hydrolyzed into the fatty acid carrier and the farnesyl transferase inhibitor (and optionally another drug) The carrier o preferably is a normal component of the central nervous system and is inactive and harmless.

00 The compound and/or drug, once released from the fatty acid carrier, is active. Preferably, the fatty acid carrier is a partially-saturated straight chain molecule having between about 16 and 26 carbon atoms, and more preferably 20 and 24 carbon atoms. Examples of fatty acid carriers Sare provided in US Patent Nos. 4,939,174; 4,933,324; 5,994,932; 6,107,499; 6,258,836 Cc and 6,407,137, the disclosures of which are incorporated herein by reference in their entirety.

IDThe administration of the agents of the present invention may be for either prophylactic C 10 or therapeutic purpose. When provided prophylactically, the agent is provided in advance of disease symptoms such as any Alzheimer's disease symptoms. The prophylactic administration of the agent serves to prevent or reduce the rate of onset of symptoms. When provided therapeutically, the agent is provided at (or shortly after) the onset of the appearance of symptoms of actual disease. In some embodiments, the therapeutic administration of the agent serves to reduce the severity and duration of Alzheimer's disease.

The function and advantage of these and other embodiments of the present invention will be more fully understood from the examples described below. The following examples are intended to illustrate the benefits of the present invention, but do not exemplify the full scope of the invention.

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EXAMPLES

O Experimental Procedures 00 Tissue culture: All cell lines were obtained by ATCC. SH-SY5Y and Cos-7 were grown in 10% FBS DMEM (Sigma). Cells were split the day before experiments including transfection, metabolic labeling and drug treatment.

SProteins and antibodies: UCH-L1 variants were purified according to the published c procedure. Synuclein antibody (SYN-1) was purchased from Signal Transduction Lab. Actin \antibody and FLAG antibody (M2) were from Sigma. UCH-L1 antibody (anti-PGP 9.5) was 0 10 from Chemicon.

Chemicals: FTI-277 and lactacystin was purchased from Calbiochem. Crosslinking reagent DE was from Pierce. DMEM and MEM were purchased from Gibco. All the other material was purchased from Sigma.

Plasmids: C220S cDNA was generated by PCR site-specific mutagenesis. For the PCR, the 5' primer is uchforw SEQ ID NO: 1 (CTAAAGCTTATGCAGCTCAAGCCGATGGAG), and 3' primer is uchc220s SEQ ID NO:2 (CTAAGA CTCGAGTTAGGCTGCCTTGCTGAGAGC). Wt UCH-L1 served as the template. The PCR fragment was inserted into pcDNA vector. For S18YC220S mutant, SI8Y UCH-L1 served as the template in PCR. For the FLAG tagged UCH-L1, the 5' primer is FLAGuchforw SEQ ID NO: 3 (CTAAAGCTTATGGACTACAAGGATGACGACGACAAAGATGCAGCTCAAGC CGATGGAG), and the 3' primer is uchrev SEQ ID NO: 4 (ATCCTCGAGTTAGGCTGCCTTGACGAGAGC). Wt UCH-L1 or C220S served as the template. PCR fragment was purified and inserted into pcDNA vector. For the FLAG tagged UCH-L3, the 5' primer is L3HindIII SEQ ID NO: 5 (CTAAAGCTTATGGACTAC AAGGATGACGACGACAAAGATGGAGGGTCAACGCTGGCTG), the 3'primer is L3XhoISAA SEQ ID NO: 6 (ATCCTCGAGCTATGCTGCAGAAAGAGCAATCGCA). For the UCH-L3 CKAA variant, the 5' primer is L3 HindIII and the 3' primer is L3XhoICKAA SEQ ID NO: 7 (ATCCTCGAGCTATGCTGCCTTAGAAAGAGCAATCGCATTAAATC).

a-synuclein degradation assay: Liphitamine 2000 was used to transfect COS-7 cells according to the Invitrogen protocol. Transfected cells were cultured at 37 °C for 48 hours before being treated with 35 uM lactacystin or DMSO. After 24 hours of incubation, the cells were lysed with Tris buffer (50 mM Tris, 2% SDS, 0.1% NP-40), and subjected to SDS-PAGE, followed by quantitative Western blotting.

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Salt and detergent treatment of SV fraction: SV fraction was prepared as describe S elsewhere. SV was incubated with various salts at designed concentration for 30 minutes on ice, o or 1% Triton X-100 or control without salts and detergent. Treated SV was pelleted at 100,000g OO for 30 minutes. Supernatants and pellets were subjected to SDS-PAGE and Western blotting.

Membrane fractionation: Cells were harvested by scraping and washed with PBS. Cell pellet was suspended in lysis buffer (50mM Tris-HCl, ImM EDTA) supplemented with 0 protease inhibitor cocktail (Sigma) and homogenized by passing through 26G needles 10 times.

c Suspension was clarified by spinning at 600g for 5 minutes. Clarified suspension was \ultracentrifuged at 100,000g for 2 hours and separated into membrane and cytosol. Membrane 0 10 fraction was washed with washing buffer (50mM Tris-HCl, ImM EDTA 1M NaCI), and pelleted each time with bench-top centrifuge.

2D electrophoresis: For the isolation of total cellular protein, cultured SH-SY5Y cells maintained as described above were rinsed with ice-cold PBS. Cells were lysed in Iml dSDS buffer (50mM Tris-HC1, pH 8.0 0.1% SDS) supplemented with protease inhibitor cocktail.

Lysates were boiled for 3 min, and were treated with Dnase and Rnase as described. Lysates were precipitated with ice-cold acetone for at least 2 hours, and pellets were resuspended in 2D sample buffer (8M urea, 0.5% CHAPS, 0.2% DTT, 0.5% IPG buffer, 0.002% bromophenol blue). 2D electrophoresis was carried out according to manufacture's protocol (Amersham Life Science). 7cm pH 4-7 strips were used. For SH-SY5Y membrane fraction, culture cells were rinsed with cold PBS and harvested with lysis buffer (50mM Tris-HC1, pH 8.0, 1mM ZnAc2, 250mM sucrose). Lysate was passed through 25G needles for several times and spun at 1000 g for 5 min. Supernatant was centrifuged at 200,000g for 2 hours. Pellet was extensively washed with lysis buffer and extracted with cold acetone. Pellet was resuspended in 2D sample buffer.

Viral Infection: Viral infection and MTT assay in SH-SY5Y cells: The viruses were amplified and purified according to the published procedure. SH-SY5Y cells were grown on 100mm petri-dishes and induced with 100nM RA for 3-5 days before the virus infection with M.I.O at 75. Viruses were diluted with DPBS to desired After four hours of incubation, 10ml growth medium was added. On the second day, cells were splitted into 96well plates and treated with compounds for next 48 hours. The growth medium in each well was replaced with growth medium with 5ug/ml MTT. Medium was removed after three hours incubation, and 200ul isopropyl (0.04N HCI) was added into each well. The signal was read at 570nm.

Viable cell counting: At stated time poins, SH-SY5Y cells were trypsinized with 100ul

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O trypsin-EDTA for 1 minute and neutralized with 400ul growth medium. Cell suspension was S made up by mixing 0.2 ml of cells in growth medium, 0.3 ml of HBSS and 0.5 ml of 0.4% O Trypan Blue solution. Viable cell numbers were counted by standard cell counting chamber.

00 Western Blotting: Following transfer of SDS gels onto NC membrane, all membranes were blocked with 5% non-fat milk in TBST (50mM Tris-HCl pH7.4, 150mM NaCI, 0.1% Tween 20), and incubated with primary antibody overnight with 1% BSA in TBST, washed \three times with TBST, and incubated with horseradish peroxidase-conjugated secondary Santibody for 1 hour (Promega). Bound antibodies were detected using enhanced o chemiluminascence (NEM).

S Example 1: UCH-L1 is farnesylated in vivo and in cell culture The UCH-L1 sequence contains the sequence CXXX, a consensus farnesylation site, at its C-terminus. This sequence is not present in UCH-L3. The possibility that this sequence was modified in vivo was investigated. First, the chemical nature of the previously reported association of UCH-L1 and synaptic vesicles from rat brain was probed.

The results are shown in Figure 1, panel Effects of various amount of salt and nonionic detergent on the dissociations of synapsin I, synaphysin and UCH-L1 from SV was analyzed by treating aliquots of SV fraction with either KC1, NaCI, MgCl 2 or 1% Triton X-100.

Membrane fraction and soluble fraction was separated by centrifugation and each fraction was subjected to SDS-PAGE followed by Western blots, a (synapsin c (synaphysin) and e (UCH- L1) are from pellet, and b (synapsin d (synaphysin) and f(UCH-L1) are supernatant fractions. Unlike synapsin (Figure 1, panel A, rows a and which is not an integral membrane protein, and like synaptophysin (rows c and UCH-L1 (rows e and f) could not be separated from the vesicular fraction by increasing salt concentration. Only treatment with detergent was sufficient to solubilize UCH-L1, consistent with its farnesylation.

Analysis of various fractions from SH-SY5Y neuroblastoma cells (similar results from rat brain, not shown) by two-dimensional SDS-PAGE gel electrophoresis showed two major and two minor species in the total homogenate and one species in the membrane-associated fraction (Figure 1 panel More than 2 forms of UCH-L1 were present in SH-SY5Y cell (gel a) detected using 2D electrophoretic analysis followed by Western blotting. Only one of them (open arrow) is associated with membrane (gel Treatment of SH-SY5Y cells with FTI-277 (gel d) results in a significant decrease in the amount of membrane bound UCH-L1 (open arrow) without affecting the amount of cytosolic UCH-L1 (close arrow) when compared to cells

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0 treated with DMSO (gel This species was presumably the fully processed species: farnesylated, truncated and C-terminally methylated.

O3 Consistent with this premise, treatment of the cells with the famesyl transferase 00 inhibitor FTI-277 decreased the amount of the membrane-associated species. In addition, a UCH-L1-containing species was immunoprecipitated from whole cell lysate by an anti-faresyl antibody (Calbiochem). Finally, treatment of the cells with 14C-mevalonic acid or with 3Ht0 farnesol resulted in incorporation of radiolabel into UCH-L1 (Figure 1, panel UCH-L1 was modified with [14C] mevalonate (gel a) and 3 H] farnesol (gel b) in vivo. Transfection \of the C220S mutant into COS-7 cells prevented radioincorporation and eliminated the 0 10 membrane-associated species (not shown). Figure 1, panel shows that WT UCH-L1 but not the C220S variant was detected in the membrane fraction of COS-7 cells transfected with either of the UCH-L1 variants).

Example 2: Removal of the farnesyltation site has no effect on the in vitro enzymatic activity or aggregation properties of UCH-L1 The C220S mutant as expressed in E. coli and purified using a published method. As expected from examination of structural models of UCH-L1, the point mutation had no effect on the in vitro hydrolase (Figure 2, panel A) or ligase (panel B) activities. Michaelis- Menten plot of various amount Ub-AMC titrated against either UCH-L1 WT (close circle) or C220S (open circle) showed comparable hydrolytic activities. The mutation does not affect UCH-L1 in vitro ligase activity. In addition, the C220S mutation did not eliminate the propensity of S18 to oligomerize. This finding cleared the way to examine the effects of C220S in cell culture.

IND

Example 3: Farnesylation and membrane association of UCH-L1 is required to promote accumulation of a-synuclein in COS-7 cells.

O 0 00 The C220S mutation eliminated the ability of S18 to promote a-synuclein accumulation in COS-7 cells but had no effect on the S18Y polymorph (Figure 2, panel the relative amount of 16kDa a-synuclein was quantified and normalized against the amount of actin in \transfected COS-7 cells with the presence of UCH-L1 variants. 100% accumulation of asynuclein was achieved in cells treated with proteasome inhibitor lactacysteine). This finding Ssuggested that famesylation and membrane attachment of UCH-L1 are both required. In order to isolate the latter possibility, a mutant form of UCH-L3 was constructed in which the UCH- L1 farnesylation sequence was added to the UCH-L3 C-terminus. This protein did not cause accumulation of a-synuclein (panel The relative amount of a-synuclein was compared among COS-7 cells transfected with UCH-L1 and UCH-L3 variants), although it was farnesylated and incorporated into the membrane (not shown). Thus, membrane attachment of an active hydrolase was insufficient to cause accumulation of a-synuclein.

Example 4: Inhibition of farnesvlation rescues cell death caused by a-synuclein overexpression in SH-SY5Y cells.

Since a-synuclein neurotoxicity is dose-dependent, it follows that accumulation of a-synuclein, caused by UCH-L1 farnesylation, should promote its toxicity. We demonstrated this to be true in mamallian neuroblastoma SH-SY5Y cells. This dopaminergic cell line has been used to demonstrate the rescue of a-synuclein toxicity by parkin, an effect that has also been demonstrated in primary dopaminergic cultures. These cells express high endogenous levels of UCH-L1. The a-synuclein gene was overexpressed (as compared to endogenous levels) via infection with an adenoviral vector and toxicity was demonstrated by the Trypan blue (Figure 3) and MTT assays (Figure Figure 3 shows SH-SY5Y cells infected by a synuclein-expressing adenovirus treated with DMSO FTI-277 LDN57414 FTI- 277 and LDN57414 Viable cell numbers were quantified by counting the cells treated with either DMSO (lower dark circles), FTI-277 (upper dark circles), LDN57414 (light triangles) or LDN57414 and FTI-277 (dark triangles) that did not stain with trypan blue. The unit of y-axis is 105 /ml. Cell viability was assessed by the amount of metabolic activity using MTT assay. Figure 4 shows: the viability of SH-SY5Y cells infected by a- 227

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synuclein-expressing adenovirus after treatment of DMSO (closed triangles) or FTI-277 (open S triangles), and of cells infected with lacZ-expressing adenovirus after treatment of DMSO O (closed circles) or FTI-277 (open circles), and of cells infected with empty adenovirus after 00 treatment of DMSO (closed squares) or FTI-277 (open squares) were assessed using MTT assay. The effect of FTI-277 on the a-synuclein accumulation in the SH-SY5Y infected with asynuclein-expressing adenovirus were analyzed by Western blotting and the amount of a- Ssynuclein was quantified using NIH Image program and normalized against the amount of c actin.

The commercially-available small molecule farnesyl transferase inhibitor FTI-277, 0 10 which had previously been shown to reduce the amount of membrane-associated, farnesylated species (Figure 1, panel B, row resulted in a significantly decreased loss of cells (compare Figure 3, panel B to panel This neuroprotective effect was eliminated by co-adminstration of the small-molecule UCH-L1 inhibitor (not shown), suggesting that the FTI effect was primarily due to its effect on UCH-L1. Treatment with FTI-277 reduced the total amount of UCH-L1 in SH-SY5Y cells and increased its rate of turnover (pulse-chase experiment not shown), in addition to reducing the amount of membrane-associated protein. This treatment also reduced the amount of a-synuclein in these cells (Figure 4, panels B and C).

The following publications describe useful farnesyl transferase inhibitor compounds, their structural and functional analogs and compositions and related synthetic methods: US 6,545,020, US 6,458,800, US 6,451,812, US 6,420,387, US 6,187,786, US 6,177,432, US 6,169,096, US 6,037,350 and US 5,968,952 and WO 2002085364, WO 2002064142, WO 2002043733, WO 2001064252, US 2003212008, WO 2001064246, US 2003022918, WO 2001064226, US 2003027808, WO 2001064218, US 2003125326, WO 2001064217, US 2003078281, WO 2001064199, US 2003181473, WO 2001064198, US 2003050323, WO 2001064197, US 2003125268, WO 2001064196, US 2003060480, WO 2001064195, US 2003186925, WO 2001064194, US 2003100553, WO 2001062234, US 2003060450, WO 2001056552, US 2003027839, WO 2000001411, US 6545020, WO 2000001386, US 6451812, WO 9855124, US 6365600, US 2002091138, WO 9721701, US 6169096, US 6420387, WO 2002024687, US 2003199547, WO 2002024686, US 2003207887, WO 2002024683, WO 2002072574, US 6358961, WO 03/080058, WO 2003041658, WO 2002085819, WO 2001072721, WO 2000042849, WO 2003076660, WO 2002080895, WO 2002072085, WO 2002056884, WO 9730992, WO 9901434, US 2003162965, US 2002169313, US 2002002162, US 6537988, US 2003134846, US 2003073677, US 2003092705, US 6645966, US 6011029, US6387926, US6602883, US6455523, US 5925757, WO 9804549, WO 2003072549, WO 8 2003047586, US 6358968, US 20022119981, WO 9857970, WO 9857962, WO 9857948, US 5719148, WO 9630363, US 6576639, US 5874442, US 6143758, US 6214828, WO 9857959, o WO 9723478, US 20040006087, US 20030229099, US 6358968, US 5939416, US 00 20020119981, US 6576639, US 6214828, US 5874442, US 6143758, US 5696121, US 5719148, US 5714609, US 5807853, US 6365588, US 20030055065, US 6242458 and US 20020068742, WO 2003092671, WO 200307660, WO 2002028409, US 2002077301, WO 2001076693, WO 2001060815, US 2002052380, WO 2001060368, US 2002010184, WO 2001032149, WO 2001007437, WO 2001005430, US 2002136744, WO 2000070083, WO IND 2000059930, US 2003220241, WO 2000025789, WO 2000025788, US 6329376, WO 2000016778, WO 2000016626, WO 2000001702, US 6562823, WO 2000001691, WO 2000001678, US 6160118, WO 9909985, US 6387903, WO 9910525, WO 9910524, WO 9910523, US 6103487, US 5859012, WO 9900654, US 6060038, US 5856326, WO 9630343, WO 9854966, WO 9844797, WO 9745412, WO 9738664, WO 9736889, WO 9736888, US 5919785, WO 9736587, and WO 9630343. The disclosures of these and all patents, patent 1 5 publications and scientific publications are incorporated by reference herein in their entirety.

Having now described some illustrative embodiments of the invention, it should be apparent to those skilled in the art that the foregoing is merely illustrative and not limiting, having been presented by way of example only. Numerous modifications and other illustrative embodiments are within the scope of one of ordinary skill in the art and are contemplated as falling within the scope of the invention. In particular, although many of the examples presented herein involve specific combinations of method acts or system elements, it should be understood that those acts and those elements may be combined in other ways to accomplish the same objectives. Acts, elements and features discussed only in connection with one embodiment are not intended to be excluded from a similar role in other embodiments. Further, for the one or more means-plus-function limitations recited in the following claims, the means are not intended to be limited to the means disclosed herein for performing the recited function, but are intended to cover in scope any means, known now or later developed, for performing the recited function. Use of ordinal terms such as "first", "second", "third", etc., in the claims to modify a claim element does not by itself connote any priority, precedence, or order of one claim element over another or the temporal order in which acts of a method are performed, but are used merely as labels to distinguish one claim element having a certain name from another element having a same name (but for use of the ordinal term) to distinguish the claim elements.

Similarly, use of etc., or ii), etc. does not by itself connote any priority, precedence, or 229 O order of steps in the claims. Similarly, the use of these terms in the specification does not by itself connote any required priority, precedence, or order.

The foregoing written specification is considered to be sufficient to enable one skilled in 00 the art to practice the invention. The present invention is not to be limited in scope by examples provided, since the examples are intended as a single illustration of one aspect of the invention and other functionally equivalent embodiments are within the scope of the invention.

O Various modifications of the invention in addition to those shown and described herein will Cc become apparent to those skilled in the art from the foregoing description and fall within the INO scope of the appended claims. The advantages and objects of the invention are not necessarily C 10 encompassed by each embodiment of the invention.

The term "comprise" and variants of the term such as "comprises" or "comprising" are used herein to denote the inclusion of a stated integer or stated integers but not to exclude any other integer or any other integers, unless in the context or usage an exclusive interpretation of the term is required.

Any reference to publications cited in this specification is not an admission that the disclosures constitute common general knowledge in Australia.

Claims (281)

1. 2. The method of claim 1, wherein the synucleinopathic subject has a synucleinopathy selected from the group consisting of Parkinson's disease, diffuse Lewy body disease, and multiple system atrophy disorder. 0
2. 3. The method of claim 1, wherein the synucleinopathic subject has Parkinson's disease.
3. 4. The method of claim 2, wherein the subject is a human. The method of claim 4, wherein the effective amount comprises about 10 ng/kg of body weight to about 1000 mg/kg of body weight at a frequency of administration from once a day to once a month.
4. 6. The method of claim 1, further comprising administering to the subject an amount of one or more non-faresyl transferase inhibitor compounds effective to treat a neurological disorder.
5. 7. The method of claim 6, wherein each non-farnesyl transferase inhibitor compound is selected from the group consisting of dopamine agonist, DOPA decarboxylase inhibitor, dopamine precursor, monoamine oxidase blocker, cathechol 0-methyl transferase inhibitor, anticholinergic, and NMDA antagonist.
6. 8. The method of claim 6, wherein each non-farnesyl trasferase inhibitor compound is selected from the group consisting of Memantine, Aricept, and other acetylcholinesterase inhibitors.
7. 9. An article of manufacture comprising packaging material and a famesyl transferase inhibitor, or a pharmaceutically acceptable salt form thereof, wherein the article of ID O manufacture further comprises a label or package insert indicating that the farnesyl transferase S inhibitor can be administered to a subject for treating a synucleinopathy. C) O 00 10. The article of manufacture of claim 9, wherein the synucleinopathy is selected from the group consisting of: Parkinson's disease, diffuse Lewy body disease, and multiple system atrophy disorder. rO
8. 11. The article of manufacture of claim 9, wherein the synucleinopathy is IN0 Parkinson's disease. S
9. 12. The article of manufacture of claim 10, further comprising one or more non- farnesyl transferase inhibitor compounds effective to treat a neurological disorder.
10. 13. The article of manufacture of claim 12, wherein each non-farnesyl transferase inhibitor compound is selected from the group consisting of dopamine agonist, DOPA decarboxylase inhibitor, dopamine precursor, monoamine oxidase blocker, cathechol 0-methyl transferase inhibitor, anticholinergic, and NMDA antagonist.
11. 14. The article of manufacture of claim 12, wherein each non-farnesyl trasferase inhibitor compound is selected from the group consisting of Memantine, Aricept, and other acetylcholinesterase inhibitors. A method of treating a synucleinopathic subject, the method comprising, administering to a synucleinopathic subject a farnesyl transferase inhibitor of formula: 232 -N or a stereoisomeric form, or a pharmaceutically acceptable acid or base addition salt form thereof, in a therapeutically effective amount.
12. 16. The method of claim 15, wherein the synucleinopathic subject has a synucleinopathy selected from the group consisting of: Parkinson's disease, diffuse Lewy body disease, and multiple system atrophy disorder.
13. 17. The method of claim 16, wherein the subject is a human.
14. 18. The method of claim 17, wherein the effective amount comprises about 1Ong/kg of body weight to about 1000mg/kg of body weight at a frequency of administration from once a day to once a month.
15. 19. The method of claim 18, further comprising administering to the subject an amount of one or more non-farnesyl transferase inhibitor compounds effective to treat a neurological disorder. The method of claim 19, wherein each non-farnesyl transferase inhibitor compound is selected from the group consisting of: dopamine agonist, DOPA decarboxylase inhibitor, dopamine precursor, monoamine oxidase blocker, cathechol 0-methyl transferase inhibitor, anticholinergic, and NMDA antagonist.
16. 21. The method of claim 19, wherein each non-farnesyl trasferase inhibitor ID O compound is selected from the group consisting of Memantine, Aricept, and other S acetylcholinesterase inhibitors. C.) O 00 22. An article of manufacture comprising packaging material and a farnesyl transferase inhibitor compound of claim 15, wherein the article of manufacture further comprises a label or package insert indicating that the faresyl transferase inhibitor compound O can be administered to a subject for treating a synucleinopathy. (c Is 23. The article of manufacture of claim 22, wherein the synucleinopathy is selected O 0 10 from the group consisting of: Parkinson's disease, diffuse Lewy body disease, and multiple system atrophy disorder.
17. 24. The article of manufacture of claim 23, further comprising one or more non- farnesyl transferase inhibitor compounds effective to treat a neurological disorder. The article of manufacture of claim 24, wherein each non-farnesyl transferase inhibitor compound is selected from the group consisting of: dopamine agonist, DOPA decarboxylase inhibitor, dopamine precursor, monoamine oxidase blocker, cathechol 0-methyl transferase inhibitor, anticholinergic, and NMDA antagonist.
18. 26. A method of treating a synucleinopathic subject, the method comprising, administering to a synucleinopathic subject a farnesyl transferase inhibitor of formula: or a stereoisomeric form, or a pharmaceutically acceptable acid or base addition salt form thereof, in a therapeutically effective amount, C.) 00 X is oxygen or sulfur; R1 is hydrogen, C- 1 12 alkyl, Arl, Ar 2C,. 6 alkyl, quinolinylC,- 6 alkyl, pyridylCI- 6 alkyl, hydroxyCI 1 6 alkyl, C1. 6 alkyloxyCI- 6 alkyl, mono- or di(C 1 6 alkyl)aminoC,-6 alkyl, aminoC 1 6 alkyl, or a radical of formula -Alk' -Alk' or -Alk' -S(0) 2 -R9, wherein Alk' is C,. 6 alkanediyl, IND R9 is hydroxy, C,- 6 alkyl, C,. 6 alkyloxy, amino, C,. 8 alkylamino or C1. 8 alkylamino substituted with C 1 6 alkyloxycarbonyl; R 2 R 3 and R 1 6 each independently are hydrogen, hydroxy, halo, cyano, C,. 6 alkyl, C,. 6 alkyloxy, hydroxyC,. 6 aikyloxy, C,. 6 aikyloxyCI- 6 alkyloxy, aminoCI. 6 alkyloxy, mono- or di(C,. 6 alkyl)aminoCI- 6 alkyloxy, Ar 1 Ar 2 CI- 6 alkyl, Ar 2 oxy, Ar 2 C 1 6 alkyloxy, hydroxycarbonyl, C, -6 alkyloxycarbonyl, trihalomethyl, trihalomethoxy, C 2 6 alkenyl, 4,4- dimethyloxazolyl; or when on adjacent positions R 2 and R 3 taken together may form a bivalent radical of formula -0-CH 2 (a-i1), -0-CR 2 -CH 2 -0-CH=CH- -0-CH 2 -CH 2 -0-CR 2 -CH 2 -CH 2 or -CH=CH-CH=CH- R 4 and R 5 each independently are hydrogen, halo, Ar', C,.6 alkyl, hydroxyC,. 6 alkyl, C,. 6 alkyioxyC 1 6 alkyl, C,1- 6 alkyloxy, C 1. 6 alkylthio, amino, hydroxycarbonyl, 6 alkyloxycarbonyl, C,. 6 aikylS(0)C,. 6 alkyl or C,. 6 alkylS(0) 2 C,. 6 alkyl; R 6 and R 7 each independently are hydrogen, halo, cyano, C,. 6 alkyl, C,. 6 alkyloxy, Ar 2 oxy, trihalomethyl, C,. 6 alkylthio, di(C,. 6 alkyl)amino, or when on adjacent positions R 6and R 7taken together may form a bivalent radical of formula -0-CR 2 or -CH=CH-CH=CH- R 8 is hydrogen, C,. 6 alkyl, cyano, hydroxycarbonyl, C,. 6 alkyloxycarbonyl, C,. 6 alkylcarbonylC,. 6 alkyl, cyanoC,. 6 alkyl, C,. 6 alkyloxycarbonylC,. 6 alkyl, carboxyC, 6 alkyl, hydroxyC 1- 6 alkyl, aminoC 1 6 alkyl, mono- or di(C 1 6 alkyl)aminoC 1- 6 alkyl, imidazolyl, haloC 1 6 alkyl, C 1 6 alkyloxyCI- 6 alkyl, aminocarbonylC,. 6 alkyl, or a radical of formula o-O-R'1 0 1), 00 0 2), -N-R1 R 1 2 3), wherein R1 0 is hydrogen, C 1 6 alkyl, C1. 6 alkylcarbonyl, Ar', Ar 2 C 1 6 alkyl, C 1 6 2 2 14 alkyloxycarbonylCI. 6 alkyl, a radical or formula -Alk 2 or -Alk 2 -NR R IND R1 is hydrogen, C1. 12 alkyl, Ar' or Ar 2 C 1 6 alkyl; R' is hydrogen, C,. 6 alkyl, C,-1 6 alkylcarbonyl, C1-6alkyloxycarbonyl, C,. 6 1 2 alkylaminocarbonyl, Ar Ar 2 C,. 6 alkyl, C,. 6 alkylcarbonylC 1 6 alkyl, a natural amino acid, Ar' carbonyl, Ar 2 C,. 6 alkylcarbonyl, aminocarbonylcarbonyl, C,. 6 alkyloxyCI. 6 alkylcarbonyl, hydroxy, C 1 6 alkyloxy, aminocarbonyl, di(Cj. 6 alkyl)aminoC 1 6 alkylcarbonyl, amino, CI- 6 alkylamino, C 1 .6 alkylcarbonylamino, or a radical of formula -Alk 2 -OR' 3 or -Alk 2 -NR'1 4 RI 5 wherein Alk 2is C,. 6 alkanediyl; R'1 3 is hydrogen, C 1 6 alkyl, C 1 6 alkylcarbonyl, hydroxyC 1 6 alkyl, Ar' or Ar 2 CI- 6 alkyl; R"14 is hydrogen, C,. 6 alkyl, Ar' or Ar 2 C,. 6 alkyl; R 15 is hydrogen, C,. 6 alkyl, C 1 6 alkylcarbonyl, Arl or Ar 2 C 1 6 alkyl; R 17is hydrogen, halo, cyano, C 1 6 alkyl, C 1 6 alkyloxycarbonyl, Ar' R'1 8 is hydrogen, C 1 6 alkyl, C 1 6 alkyloxy or halo; R1 9 is hydrogen or CI- 6 alkyl; Ar' is phenyl or phenyl substituted with CI- 6 alkyl, hydroxy, amino, C 1 6 alkyloxy or halo; and Ar 2is phenyl or phenyl substituted with C,. 6 alkyl, hydroxy, amino, CI. 6 alkyloxy or halo.
19. 27. The method of claim 26, wherein X is oxygen.
20. 28. The method of claim 27, wherein the dotted line represents a bond.
21. 29. The method of claim 28, wherein R' is hydrogen, C 1 6 alkyl, C 1 6 alkyloxyC,. 6 236 alkyl or mono- or di(C1. 6 alkyl)aminoC,- 6 alkyl. The method of claim 29, wherein R 3is hydrogen and R 2is halo, C 1 6 alkyl, C 26 00 alkenyl, CI- 6 alkyloxy, trihalomethoxy or hydroxyCI- 6 alkyloxy.
22. 31. The method of claim 30, wherein R 8is hydrogen, hydroxy, haloC 1 6 alkyl, hydroxyCI- 6 alkyl, cyanoCI- 6 alkyl, C,- 6 alkyloxycarbonylC,. 6 alkyl, imidazolyl, or a radical of formula -NR" R 1 2 wherein R" is hydrogen or CI-1 2 alkyl and R 1 2 is hydrogen, C 1 6 alkyl, C 1 6 INDalkyloxy, CI- 6 alkyloxyC,- 6 alkylcarbonyl, hydroxy, or a radical of formula -Alk 2 -OR' wherein R' is hydrogen or C,. 6 alkyl.
23. 32. The method of claim 26, wherein the compound is 6-[amino(4-chlorophenyl)- 1-methyl-I H-imidazol-5-ylmethyl]-4-(3-chlorophenyl)- 1- methyl-2( 1 H)-quinolinone; 4-(3 -chlorophenyl)-6-[(4-chlorophenyl)hydroxy( I-methyl- I H-imidazol-5-yl)methyl]- 1 methyl-2( 1 H)-quinolinone, 6-[4-chlorophenyl)hydroxy(1 -methyl- I H-imidazol-5-yl)methyl]-4-(3-ethoxyphenyl)- 1 methyl-2(l H)-quinolinone; 6-[(4-chlorophenyl)( 1-methyl- I H-imidazol-5-yi)methyl]-4-(3-ethoxyphenyl)- 1 -methyl- 2(1 H)-quinolinone monohydrochloride.monohydrate; 6-[amino(4-chlorophenyl)(1 -methyl- I H-imidazol-5-yl)methyl]-4-(3-ethoxyphenyl)- I methyl-2(1 H)-quinolinone, and 6-amino(4-chlorophenyl)( 1-methyl- I H-imidazol-5-yl)methyl]- I -methyl-4-(3- propylphenyl)-2( 1 H)-quinolinone; or a stereoisomeric form thereof, or a pharmaceutically acceptable acid or base addition salt thereof.
24. 33. The method of claim 32, wherein the compound is (B)-6-[amino(4-chlorophenyl)( 1-methyl-i H-imidazol-5-yl)methyl]-4-(3- chlorophenyl)- I -methyl-2(1 H)-quinolinone; or a pharmaceutically acceptable acid addition salt thereof.
25. 34. A method of treating a synucleinopathic subject, the method comprising, administering to a synucleinopathic subject a farnesyl transferase inhibitor of formula: R3 R16 SR2- R HNR 0 N R -R N R19 R or a stereoisomeric form, or a pharmaceutically acceptable acid or base addition salt form thereof, in a therapeutically effective amount, wherein R 2, R and R' 6 each independently are hydrogen, hydroxy, halo, cyano, C-6 alkyl, C,. 6 alkyloxy, hydroxyC,- 6 alkyloxy, C 1 6 alkyloxyC,- 6 alkyloxy, aminoC 6 alkyloxy, mono- or di(C.-6 alkyl)aminoC. 6 alkyloxy, Ar', Ar 2 C 1 6 alkyl, Ar 2 oxy, Ar 2 Cl-6 alkyloxy, hydroxycarbonyl, CI- 6 alkyloxycarbonyl, trihalomethyl, trihalomethoxy, C2- 6 alkenyl, 4,4- dimethyloxazolyl; or when on adjacent positions R 2 and R 3 taken together may form a bivalent radical of formula -O-CH 2 -O-CH 2 -CH 2 -O-CH=CH- -O-CH 2 -CH 2 -O-CH 2 -CH 2 -CH 2 or -CH=CH-CH=CH- R 4 and R 5 each independently are hydrogen, halo, Ar', CI- 6 alkyl, hydroxyCI 6 alkyl, C 1 6 alkyloxyCI 6 alkyl, CI- 6 alkyloxy, C 1 -6 alkylthio, amino, hydroxycarbonyl, CI-. 6 alkyloxycarbonyl, C 16 alkylS(O)CI. 6 alkyl or C 1 6 alkylS(O) 2 C,. 6 alkyl; R6 and R 7 each independently are hydrogen, halo, cyano, CI- 6 alkyl, C. 6 alkyloxy, Ar2 oxy, trihalomethyl, C1- 6 alkylthio, di (C 1 6 alkyl) amino, or when on adjacent positions R 6 and R 7 taken together may form a bivalent radical of formula 238 -O-CH 2 or -CH=CH-CH=CH- C.R 8 oCR is hydrogen, C 1 6 alkyl, cyano, hydroxycarbonyl, CI-6 alkyloxycarbonyl, C,. 6 00 alkylcarbonylC 1 6 alkyl, cyanoCI. 6 alkyl, C 1 6 alkyloxycarbonylC 1 6 alkyl, carboxyCI. 6 alkyl, hydroxyCi. 6 alkyl, aminoC,. 6 alkyl, mono- or di(CI. 6 alkyl)aminoC,. 6 alkyl, imidazolyl, haloC 1 6 alkyl, C 1 6 alkyloxyCI- 6 alkyl, aminocarbonylCI. 6 alkyl, or a radical of formula 1), 2), ID-N-R"R1'R 3), wherein R' 0 is hydrogen, C 1 6 alkyl, C 1 6 alkylcarbonyl, Ar', Ar 2 C 1 6 alkyl, CI- 6 alkyloxycarbonylC. 6 alkyl, a radical or formula -Alk 2 or -Alk 2 -NR" 4 R" R1 is hydrogen, CI- 12 alkyl, Ar' or Ar 2 C,. 6 alkyl; R'1 2 is hydrogen, C 1 6 alkyl, C 1 6 alkylcarbonyl, C,. 6 alkyloxycarbonyl, C 1 6 alkylaminocarbonyl, Ar Ar 2 C 1 6 alkyl, C 1. 6 alkylcarbonylCl1.6 alkyl, a natural amino acid, Ar 1 carbonyl, Ar 2 C 1 6 alkylcarbonyl, aminocarbonylcarbonyl, C,. 6 alkyloxyC 1 6 alkylcarbonyl, hydroxy, C 1 6 alkyloxy, aminocarbonyl, di(CI- 6 alkyl) aminoC 1 6 alkylcarbonyl, amino, C,. 6 alkylamino, C 1 6 alkylcarbonylamino, or a radical of formula -Alk 2 -OR'1 3 or -Alk 2 -NR'1 4 R1 5 0 wherein Alk 2 is C 1 6 alkanediyl; R 1 3 is hydrogen, C 1 6 alkyl, C 1 6 alkylcarbonyl, hydroxyC 1 6 alkyl, Ar' or Ar 2 C 1-6 alkyl; R'1 4 is hydrogen, C,. 6 alkyl, Ar' or Ar 2 CI-6 alkyl; R 1 5 is hydrogen, C,. 6 alkyl, C 1 6 alkylcarbonyl, Ar 1 or Ar 2 C 1 6 alkyl; R 17is hydrogen, halo, cyano, C 1 6 alkyl, C,. 6 alkyloxycarbonyl, Ar, R 18is hydrogen, C,. 6 alkyl, C, 6 alkyloxy or halo; R' 9 is hydrogen or C 1 6 alkyl. A method of treating a synucleinopathic subject, the method comprising, administering to a synucleinopathic subject a famnesyl transferase inhibitor of formula: 239 Cl R 5 '-N 00 RR 0 or a stereoisomeric form, or a pharmaceutically acceptable acid or base addition salt form thereof, in a therapeutically effective amount, wherein R 2 R 3 and R 1 6 each independently are hydrogen, hydroxy, halo, cyano, C 1 6 alkyl, CI- 6 alkyloxy, hydroxyCI- 6 alkyloxy, C 1 6 alkyloxyCI- 6 alkyloxy, aminoC 1 6 alkyloxy, 1 222 mono- or di(CI. 6 alkyl)aminoC 1 6 alkyloxy, Ar Ar C 16 alkyl, Ar 2 oxy, Ar 2 C 1 6 alkyloxy, hydroxycarbonyl, C 1 6 alkyloxycarbonyl, trihalomethyl, trihalomethoxy, C 2 6 alkenyl, 4,4- dimethyloxazolyl; or when on adjacent positions R 2 and R 3 taken together may form a bivalent radical of formula -0-CH 2 (a-i1), -O-CH 2 -CH 2 -0-CH=CH- -O-CH 2 -CH 2 -0-CH 2 -CH 2 -CH 2 or -CH=CH-CH=CH- R 4 and R 5 each independently are hydrogen, halo, Arl, C 1 -6 alkyl, hydroxyC 16 alkyl, Cl- 6 alkyloxyC 1 6 alkyl, C 1 6 alkyloxy, C 1 6 alkylthio, amino, hydroxycarbonyl, C 1 6 alkyloxycarbonyl, C 1 6 alkylS(0)C 1 6 alkyl or C 1 6 alkylS(0) 2 C 1 6 alkyl; R 6 and R 7 each independently are hydrogen, halo, cyano, C 1 6 alkyl, C 1 6 alkyloxy, Ar 2 oxy, trihalomethyl, C 1 6 alkylthio, di (C 1 6 alkyl) amino, or when on adjacent positions R 6 and R 7 taken together may form a bivalent radical of 240 formula _-O-CH 2 -0-(c1,o 0C=HC=H 00 R 8 is hydrogen, C,- 6 alkyl, cyano, hydroxycarbonyl, C,-6 alkyloxycarbonyl, C,- 6 alkylcarbonylC,- 6 alkyl, cyanoC,- 6 alkyl, C,. 6 alkyloxycarbonylC,- 6 alkyl, carboxyC,. 6 alkyl, hydroxyC 1 6 alkyl, aminoC 1 6 alkyl, mono- or di (C 1 6 alkyl)aminoC 1 6 alkyl, imidazolyl, haloC 1 6 alkyl, C 1- 6 alkyloxyC 1 6 alkyl, aminocarbonylC 1 6 alkyl, or a radical of formula 1), 2), -N-R"1 R' 3), wherein R1 0 is hydrogen, CI- 6 alkyl, C,- 6 alkylcarbonyl, Arl, Ar 2 C,. 6 alkyl, CI. 6 alkyloxycarbonylC,. 6 alkyl, a radical or formula -Alk 2-OR'1 3 or -Alk 2 -NR 14R" R1 is hydrogen, CI-1 2 alkyl, Ar' or Ar 2 C,. 6 alkyl; R 12is hydrogen, C,. 6 alkyl, CI-1 6 alkylcarbonyl, C,. 6 alkyloxycarbonyl, C,. 6 alkylaminocarbonyl, Ar 1 Ar 2 C,. 6 alkyl, C,. 6 alkylcarbonylC,. 6 alkyl, a natural amino acid, Ar' carbonyl, Ar 2 C,.6 alkylcarbonyl, aminocarbonylcarbonyl, C,. 6 alkyloxyCI. 6 alkylcarbonyl, hydroxy, C, 4 6 alkyloxy, aminocarbonyl, di(C,. 6 alkyl)aminoC,.. 6 alkylcarbonyl, amino, C,. 6 alkylamino, C,. 6 alkylcarbonylamino, or a radical of formula -Alk 2 -OR" 3 or -Alk 2 -NR 1 4 RI 5 wherein Alk 2 is C,. 6 alkanediyl; R'1 3 is hydrogen, C,. 6 alkyl, C,. 6 alkylcarbonyl, hydroxyCI- 6 alkyl, Ar' or Ar 2 C,1- alkyl; R 1 4 is hydrogen, CI- 6 alkyl, Ar' or Ar 2 C,. 6 alkyl; R 1 5 is hydrogen, C,. 6 alkyl, C,. 6 alkylcarbonyl, Ar' or Ar 2 C,1. 6 alkyl; R 1 7 is hydrogen, halo, cyano, C,. 6 alkyl, C,. 6 alkyloxycarbonyl, Ar' R 1 8 is hydrogen, C,. 6 alkyl, C,. 6 alkyloxy or halo; R1 9 is hydrogen or C,. 6 alkyl.
26. 36. The method of any of claims 26-35, wherein the effective amount comprises about 10 nglkg of body weight to about 1000 mg/kg of body weight at a frequency of administration from once a day to once a month. ID
27. 37. The method of claim 36, further comprising administering to the subject an amount of one or more non-farnesyl transferase inhibitor compounds effective to treat a O neurological disorder. 00
28. 38. The method of claim 37, wherein each non-farnesyl transferase inhibitor compound is selected from the group consisting of: dopamine agonist, DOPA decarboxylase Sinhibitor, dopamine precursor, monoamine oxidase blocker, cathechol 0-methyl transferase c inhibitor, anticholinergic, and NMDA antagonist. IO 0 10 39. An article of manufacture comprising packaging material and an farnesyl transferase inhibitor compound according to any one of claims 26-35, wherein the article of manufacture further comprises a label or package insert indicating that the farnesyl transferase inhibitor compound can be administered to a subject for treating a synucleinopathy.
29. 40. The article of manufacture of claim 38, wherein the synucleinopathy is selected from the group consisting of: Parkinson's disease, diffuse Lewy body disease, and multiple system atrophy disorder.
30. 41. The article of manufacture of claim 40, further comprising one or more non- farnesyl transferase inhibitor compounds effective to treat a neurological disorder.
31. 42. The article of manufacture of claim 41, wherein each non-farnesyl transferase inhibitor compound is selected from the group consisting of: dopamine agonist, DOPA decarboxylase inhibitor, dopamine precursor, monoamine oxidase blocker, cathechol 0-methyl transferase inhibitor, anticholinergic, and NMDA antagonist.
32. 43. A method of treating a synucleinopathic subject, the method comprising, administering to a synucleinopathic subject a farnesyl transferase inhibitor of formula: 242 R 3 R 16 c-I N 0 0R8 X N R 1 9 R or a stereoisomeric form, or a pharmaceutically acceptable acid or base addition salt form thereof, in a therapeutically effective amount, wherein the dotted line represents an optional bond; X is oxygen or sulfur; R1 is hydrogen, CI 1 2 alkyl, Ar', Ar 2 C,- 6 alkyl, quinolinylC,. 6 -alkyl, pyridylC,. 6 alkyl, hydroxyCI. 6 alkyl, C,. 6 alkyloxyC,- 6 alkyl, mono- or di(C,. 6 alkyl)aminoC,- 6 alkyl, aminoC,- 6 alkyl, or a radical of formula -Alk' -Alk' -S(O)-R 9 or -Alk'-S(O) 2 R', wherein Alk' is C,. 6 alkanediyl, R 9 is hydroxy, C,. 6 alkyl, C,. 6 alkyloxy, amino, C,. 8 alkylamino or C,. 8 alkylamino substituted with C,. 6 alkyloxycarbonyl; R 2 R 3 and R 1 6 each independently are hydrogen, hydroxy, halo, cyano, C,. 6 alkyl, C,. 6 alkyloxy, hydroxyC 1- 6 alkyloxy, C,1. 6 alkyloxyC 1- 6 alkyloxy, aminoC 1- 6 alkyloxy, mono- or di(C,. 6 alkyl)aminoC,. 6 alkyloxy, Ar 1 Ar 2 CI. 6 alkyl, Ar 2 oxy, Ar 2 C,. 6 alkyloxy, hydroxycarbonyl, C, 6 alkyloxycarbonyl, trihalomethyl, trihalomethoxy, C 2 6 alkenyl, 4,4- dimethyloxazolyl; or when on adjacent positions R 2 and R 3 taken together may form a bivalent radical of formula -O-CH 2 (a-i1), -O-CH 2 -CH 2 -O-CH=CH- -O-CH 2 -CH 2 -O-CH 2 -CH 2 -CH 2 or -CH=CH-CH=CH- R 4 is hydrogen or C,. 6 alkyl; R 5 is hydrogen; R R 6 and R 7 each independently are hydrogen, halo, cyano, C 1 6 alkyl, C,. 6 alkyloxy, Ar2 C) 00 when on adjacent positions R 6 and R 7 taken together may form a bivalent radical of formula: -O-CH 2 or -CH=CH-CH=CH- Ris hydrogen, C 1 6 alkyl, cyano, hydroxycarbonyl, C 1 .6 alkyloxycarbonyl, C,. 6 alkylcarbonylC 1 6 alkyl, cyanoC,. 6 alkyl, C,. 6 alkyloxycarbonylC,. 6 alkyl, carboxyCI. 6 alkyl, hydroxyC 1 6 alkyl, aminoC 1 6 alkyl, mono- or di(C 1- 6 alkyl)aminoC 1- 6 alkyl, imidazolyl, haloC 1 6 alkyl, C,1- 6 alkyloxyC 1- 6 alkyl, aminocarbonylC 1 6 alkyl, or a radical of formula: -O-R' 0 -S-R' 0 R 12(b-3), wherein R1 0 is hydrogen, C 1 6 alkyl, CI. 6 alkylcarbonyl, Arl, Ar 2 C,. 6 alkyl, C 1 6 alkyloxycarbonylCI. 6 alkyl, a radical or formula Alk 2 OR'" or Alk 2--NR" R1 5 R 1 is hydrogen, CI-1 2 alkyl, Ar' or Ar 2 C 1 6 alkyl; R 12is hydrogen, C 1 6 alkyl, C,. 6 alkylcarbonyl, C,. 6 alkyloxycarbonyl, C 1 6 alkylaminocarbonyl, Arl, Ar 2 C,. 6 alkyl, C 1 6 alkylcarbonylC 1 6 alkyl, a natural amino acid, Ar' carbonyl, Ar 2 C,. 6 alkylcarbonyl, aminocarbonylcarbonyl, C 1 6 alkyloxyCI- 6 alkylcarbonyl, hydroxy, C 1 6 alkyloxy, aminocarbonyl, di(C,. 6 alkyl) aminoC,. 6 alkylcarbonyl, amino, C 1 6 alkylamino, C,. 6 alkylcarbonylamino, or a radical of formula Alk 2 or -Alk 2 -NR 1 4 R1 5 wherein Alk 2is CI- 6 alkanediyl; R'1 3 is hydrogen, C 1 6 alkyl, 6 alkylcarbonyl, hydroxyC 1. 6 alkyl, Ar' or Ar 2 C 1- alkyl; R 14is hydrogen, C 1 6 alkyl, Arl or Ar C,. 6 alkyl; R 15is hydrogen, C,. 6 alkyl, C 1 6 alkylcarbonyl, Arl or Ar 2Cb-6 alkyl; R 17is hydrogen, halo, cyano, C,. 6 alkyl, C,. 6 alkyloxycarbonyl, Ar' R 1 8 is hydrogen, C 1 6 alkyl, C 1 6 alkyloxy or halo; R1 9 is hydrogen or C,. 6 alkyl; Arl is phenyl or phenyl substituted with C 1 6 alkyl, hydroxy, amino, C,. 6 alkyloxy or halo; and Ar 2is phenyl or phenyl substituted with C 1 6 alkyl, hydroxy, amino, C,. 6 alkyloxy or halo. 244 The method of claim 43, wherein X is oxygen. C.) 00 45. The method of claim 44, wherein R 6 is C 1 -6 alkyl or halo; and R 7 is hydrogen.
33. 46. The compound of claim 45, wherein R1 is hydrogen, C 1 6 alkyl, C 14 6 alkyloxyCI. 6 alkyl, di(CI- 6 alkyl)aminoCi- 6 alkyl, or a radical of formula Alk' 9 wherein Alk' is methylene and R 9 is C 1 -8 alkylamino substituted with CI- 6 alkyloxycarbonyl; R 2 is halo, CI- 6 alkyl, C 2 6 alkenyl, C 1 6 alkyloxy, trihalomethoxy, hydroxyCI- 6 alkyloxy or ArI R 3 is hydrogen; R 4 is methyl bound to the nitrogen in 3-position of the imidazole; R 5 is hydrogen; R 6is chloro; R 7 is hydrogen; R 8 is hydrogen, hydroxy, haloC 1 6 alkyl, hydroxyC 1 6 alkyl, cyanoC 1 6 alkyl, C 14 6 alkyloxycarbonylC 1 6 alkyl, imidazolyl, or a radical of formula NR" R 1 2 wherein RI" is hydrogen or CI- 12 alkyl and R 1 2 is hydrogen, CI- 6 alkyl, C 1 6 alkyloxy, C 1 6 alkyloxyC 1 6 alkylcarbonyl, or a radical of formula Alk 2 OR' 3 wherein R 1 3 is C 1 6 alkyl; R 1 7 is hydrogen; and R 1 8 is hydrogen.
34. 47. The compound of claim 46, selected from CI _N 0 /N 00 HO O O or Cl HO O-N N or a stereoisomeric form thereof, or a pharmaceutically acceptable acid or base addition salt thereof.
35. 48. The method of any of claims 43-47, wherein the effective amount comprises about 10 ng/kg of body weight to about 1000 mg/kg of body weight at a frequency of administration from once a day to once a month.
36. 49. The method of claim 48, further comprising administering to the subject an amount of one or more non-faresyl transferase inhibitor compounds effective to treat a neurological disorder. IO The method of claim 49, wherein each non-famesyl transferase inhibitor O compound is selected from the group consisting of: dopamine agonist, DOPA decarboxylase 00 inhibitor, dopamine precursor, monoamine oxidase blocker, cathechol 0-methyl transferase inhibitor, anticholinergic, and NMDA antagonist. \O 51. An article of manufacture comprising packaging material and a farnesyl transferase inhibitor compound according to any of claims 43-47, wherein the article of INO manufacture further comprises a label or package insert indicating that the farnesyl transferase O 0 10 inhibitor compound can be administered to a subject for treating a synucleinopathy.
37. 52. The article of manufacture of claim 51, wherein the synucleinopathy is selected from the group consisting of: Parkinson's disease, diffuse Lewy body disease, and multiple system atrophy disorder.
38. 53. The article of manufacture of claim 52, further comprising one or more non- famesyl transferase inhibitor compounds effective to treat a neurological disorder.
39. 54. The article of manufacture of claim 53, wherein each non-farnesyl transferase inhibitor compound is selected from the group consisting of: dopamine agonist, DOPA decarboxylase inhibitor, dopamine precursor, monoamine oxidase blocker, cathechol 0-methyl transferase inhibitor, anticholinergic, and NMDA antagonist. A method of treating a synucleinopathic subject, the method comprising, administering to a synucleinopathic subject a farnesyl transferase inhibitor that is an enantiomer of 6-(amino(4-chlorophenyl)( 1-methyl-1 H-imidazol-5-yl)methyl)-4-(3 -chlorophenyl)-1 -methyl- 2(IH)-quinolinone having an aD 2 0 value of +22.860 (c=49.22 mg/5 ml, methanol) or a pharmaceutically acceptable acid addition salt thereof.
40. 56. The method of claim 55, wherein the effective amount comprises about 10 ng/kg of body weight to about 1000 mg/kg of body weight at a frequency of administration from once a day to once a month.
41. 57. The method of claim 56, further comprising administering to the subject an ID amount of one or more non-faresyl transferase inhibitor compounds effective to treat a neurological disorder. C) O 00 58. The method of claim 57, wherein each non-farnesyl transferase inhibitor compound is selected from the group consisting of: dopamine agonist, DOPA decarboxylase inhibitor, dopamine precursor, monoamine oxidase blocker, cathechol 0-methyl transferase Sinhibitor, anticholinergic, and NMDA antagonist. (cl
42. 59. An article of manufacture comprising packaging material and a farnesyl 0 10 transferase inhibitor compound according to claim 55, wherein the article of manufacture further comprises a label or package insert indicating that the farnesyl transferase inhibitor compound can be administered to a subject for treating a synucleinopathy. The article of manufacture of claim 59, wherein the synucleinopathy is selected from the group consisting of: Parkinson's disease, diffuse Lewy body disease, and multiple system atrophy disorder.
43. 61. The article of manufacture of claim 60, further comprising one or more non- farnesyl transferase inhibitor compounds effective to treat a neurological disorder.
44. 62. The article of manufacture of claim 61, wherein each non-farnesyl transferase inhibitor compound is selected from the group consisting of: dopamine agonist, DOPA decarboxylase inhibitor, dopamine precursor, monoamine oxidase blocker, cathechol 0-methyl transferase inhibitor, anticholinergic, and NMDA antagonist.
45. 63. A method of treating a synucleinopathic subject, the method comprising, administering to a synucleinopathic subject a farnesyl transferase inhibitor of formula: 00 R 7 or a stereoisomeric form, or a pharmaceutically acceptable acid or base addition salt form thereof, in a therapeutically effective amount, wherein the dotted line represents an optional bond; X is oxygen or sulfur; R' and R 2 each independently are hydrogen, hydroxy, halo, cyano, C,. 6 alkyl, trihalomethyl, trihalomethoxy, C 2 6 alkenyl, C,. 6 alkyloxy, hydroxyCI- 6 alkyloxy, C,. 6 alkyloxyC,- 6 alkyloxy, C,. 6 alkyloxycarbonyl, aminoC,- 6 alkyloxy, mono- or di(C,. 6 alkyl)aminoC,- 6 alkyloxy, Ar Ar 1 C,-6 alkyl, Arl oxy, Arl CI. 6 alkyloxy; R 3 and R 4 each independently are hydrogen, halo, cyano, C,. 6 alkyl, CI. 6 alkyloxy, Ar' OXY, C 1 6 alkylthio, di(C,-6 alkyl)amino, trihalomethyl or trihalomethoxy; R 5 is hydrogen, halo, 6 alkyl, cyano, haloC 1. 6 alkyl, hydroxyC 1 6 alkyl, cyanoC 1 6 alkyl, aminoC,- 6 alkyl, C,. 6 alkyloxyC,. 6 alkyl, C,. 6 alkylthioCI- 6 alkyl, aminocarbonylC,. 6 alkyl, C,. 6 alkyloxycarbonylC,. 6 alkyl, C,. 6 alkylcarbonylC,. 6 alkyl, C,1- 6 alkyloxycarbonyl, mono- or di(C 1 6 alkyl)aminoC 1 6 alkyl, Ar I, Ar' C,. 6 alkyloxyC,. 6 alkyl; or a radical of formula: 0 1), -S-R' 0 2), -N-R1 1 R'1 2 3), wherein R1 0 is hydrogen, C,. 6 alkyl, C,. 6 alkylcarbonyl, Arl, Arl C,. 6 alkyl, C,. 6 alkyloxycarbonylC,. 6 alkyl, or a radical of formula Alk--OR 1 3 or Alk--NR 1 4 R1 5 R1 is hydrogen, C 1 6 alkyl, Ar' or Arl C 1 6 alkyl; R_ 1 2 is hydrogen, CI- 6 alkyl, C 1 6 alkylcarbonyl, C,. 6 alkyloxycarbonyl, C 1 6 C) 00 Ar 1 C 1 .6 alkylcarbonyl, aminocarbonylcarbonyl, C,. 6 alkyloxyCI. 6 alkylcarbonyl, hydroxy, C 1 6 alkyloxy, aminocarbonyl, di(C,. 6 alkyl)aminoC,. 6 alkylcarbonyl, amino, C 1 6 alkylamino, C 1 6 alkylcarbonyl amino, or a radical or formula Alk-- OR'" or Alk--NR'1 4 R's wherein Alk is C 1 6 alkanediyl; 3 Ris hydrogen, C,. 6 alkyl, C1. 6 alkylcarbonyl, hydroxyCI. 6 alkyl, Ar' or Ar' C 1 .6 alkyl; R' is hydrogen, C 1 6 alkyl, Ar' or Ar' C 1 6 alkyl; R '5 is hydrogen, CI- 6 alkyl, CI- 6 alkylcarbonyl, Ar' or Ar' C 1 6 alkyl; R 6 is a radical of formula: N -N R6 (b-i1) N R(b-2) wherein R'1 6 is hydrogen, halo, Ar', C,. 6 alkyl, hydroxyC,. 6 alkyl, C 1 6 alkyloxyC 1 6 alkyl, C,. 6 alkyloxy, C,. 6 alkylthio, amino, C 1 6 alkyloxycarbonyl, C 1 6 alkylthioC 1 6 alkyl, C 1 6 alkylS(O)C,. 6 alkyl or C,. 6 alkylS(O) 2 C 1 6 alkyl; R 1 7 is hydrogen, C,. 6 alkyl or di(C 14 alkyl)aminosulfonyl; R 7 is hydrogen or CI. 6 alkyl provided that the dotted line does not represent a bond; R 8 is hydrogen, C 1 6 alkyl or Ar 2CH 2 or Het'1 CH 2 R 9 is hydrogen, C,. 6 alkyl, C 1 6 alkyloxy or halo; or R 8 and R 9 taken together to form a bivalent radical of formula -CH=CH- (c-I) -CH 2 -CH 2 (c-2) -CH 2 -CH 2 -CH 2 (c-3) ID -CH 2 or -CH 2 -CH 2 O Ar' is phenyl; or phenyl substituted with 1 or 2 substituents each independently selected 00 from halo, C.-6 alkyl, C1- 6 alkyloxy or trifluoromethyl; 2 Ar is phenyl; or phenyl substituted with 1 or 2 substituents each independently selected from halo, CI- 6 alkyl, C.-6 alkyloxy or trifluoromethyl; and SHet' is pyridinyl; pyridinyl substituted with 1 or 2 substituents each independently selected from halo, Ci. 6 alkyl, CI- 6 alkyloxy or trifluoromethyl. S64. The method according to claim 63, wherein R' and R 2 are each independently 0 10 selected from hydrogen, halo or C 1 4 alkyl, R and R 4 are each independently selected from hydrogen, halo or C-4 alkyl, R 5 is hydrogen, hydroxy, halo or a amino; R 6 is a radical of formula or wherein R 16 is hydrogen or C-4 alkyl and R 1 7 is C- 4 alkyl; R 7 is hydrogen or C-4 alkyl in case the dotted line does not represent a bond; R 8 is hydrogen; C 1 4 alkyl or Het' CH 2 and R 9 is hydrogen. The method according claim 63, wherein X is oxygen, R' is 3-chloro, R 2 is hydrogen, R 3 is 4-chloro, R 4 is hydrogen, R 5 is hydrogen, CI. 2 alkyl, halo or amino; R 6 is a radical of formula or wherein R 16 is hydrogen and R 17 is CI- 2 alkyl; and R 7 is hydrogen or Cl-2 alkyl in case the dotted line does not represent a bond; R 8 is hydrogen; C-. 2 alkyl or Het' CH 2 and R 9 is hydrogen.
46. 66. The method according to claim 63, wherein the compound is 6-[amino(4-chlorophenyl)( -methyl-1H-imidazol-5-yl)methyl]-4-(3- chlorophenyl)-1 -methyl-2(1H)-quinazolinone; or 6-[amino(4-chlorophenyl)(1-methyl- H-imidazol-5-yl)methyl]-4-(3- chlorophenyl)-3,4-dihydro- 1,3-dimethyl-2(1 H)-quinazolinone; or a stereoisomeric form, or a pharmaceutically acceptable acid addition salt thereof.
47. 67. A method of treating a synucleinopathic subject, the method comprising, administering to a synucleinopathic subject a farnesyl transferase inhibitor of formula: ID R2 R 4 SR 1 R3 O o (CH2)n N 00' O or a stereoisomeric form, or a pharmaceutically acceptable acid or base addition salt form thereof, in a therapeutically effective amount, wherein n is 2 or 3 and R 2 R 3 R 4 and R 9 are as defined in claim El.
48. 68. The method of any of claims 63-47, wherein the effective amount comprises about 10 ng/kg of body weight to about 1000 mg/kg of body weight at a frequency of administration from once a day to once a month.
49. 69. The method of claim 68, further comprising administering to the subject an amount of one or more non-farnesyl transferase inhibitor compounds effective to treat a neurological disorder. The method of claim 69, wherein each non-farnesyl transferase inhibitor compound is selected from the group consisting of: dopamine agonist, DOPA decarboxylase inhibitor, dopamine precursor, monoamine oxidase blocker, cathechol 0-methyl transferase inhibitor, anticholinergic, and NMDA antagonist.
50. 71. An article of manufacture comprising packaging material and a farnesyl transferase inhibitor compound according to any of claims 63-67, wherein the article of manufacture further comprises a label or package insert indicating that the farnesyl transferase inhibitor compound can be administered to a subject for treating a synucleinopathy. I O O S 10 (-N 252
51. 72. The article of manufacture of claim 71, wherein the synucleinopathy is selected from the group consisting of: Parkinson's disease, diffuse Lewy body disease, and multiple system atrophy disorder.
52. 73. The article of manufacture of claim 72, further comprising one or more non- farnesyl transferase inhibitor compounds effective to treat a neurological disorder.
53. 74. The article of manufacture of claim 73, wherein each non-farnesyl transferase inhibitor compound is selected from the group consisting of: dopamine agonist, DOPA decarboxylase inhibitor, dopamine precursor, monoamine oxidase blocker, cathechol 0-methyl transferase inhibitor, anticholinergic, and NMDA antagonist. A method of treating a synucleinopathic subject, the method comprising, administering to a synucleinopathic subject a farnesyl transferase inhibitor of formula: or a stereoisomeric form, or a pharmaceutically acceptable acid or base addition salt form thereof, in a therapeutically effective amount, wherein the dotted line represents an optional bond; X is oxygen or sulfur; is a bivalent radical of formula: -CH=CH- 253 IND-H- a-) CH 2 -CH 2 0C20 00 -CH 2 -CH 2 -CH 2 -CH 2 -CH 2 or IND ~-CO-NH- R1 and R 2 each independently are hydrogen, hydroxy, halo, cyano, C 1 6 alkyl, trihalomethyl, trihalomethoxy, C 2 6 alkenyl, C1-6 alkyloxy, hydroxy C 1 6 alkyloxy, C 1 6 alkyloxyCI. 6 alkyloxy, C 1 6 alkyloxycarbonyl, aminoC 1 6 alkyloxy, mono- or di(C 1 6 alkyl)aminoC 1 6 alkyloxy, Ar 2, Ar2 Cr- 6 alkyl, Ar 2-oxy, Ar 2 C 1 6 alkyloxy; or when on adjacent positions R' and R 2 taken together may form a bivalent radical of formula: -O-CH 2 (b-I1), -O-CH 2 -CH 2 -O-CH=CH- -O-CH 2 -CH 2 -O-CH 2 -CH 2 -CH 2 or -CH=CH-CH=CH- R 3 and R 4 each independently are hydrogen, halo, cyano, C I 6 alkyl, C I 6 alkoxy, Ar -_oxy, CI. 6 alkylthio, di(CI. 6 alkyl)amino, trihalomethyl, trihalomethoxy, or when on adjecent positions R 3 and R 4 taken together may form a bivalent radical of formula: -O-CH 2 -O-CH 2 -CH 2 or -CH=CH-CH=CH- R 5 is a radical of formula: N R. N J (d-1) N IND R(d-2) wherein R' is hydrogen, halo, Ar 4 C 1 6 alkyl, hydroxyCI. 6 alkyl, C 1 6 alkyloxyC 1 6 alkyl, C 1 6 alkyloxy, C 1 6 alkylthio, amino, C 1 6 alkyloxycarbonyl, C 1 6 alkylS(O)CI. 6 alkyl or C 1 6 alkylS(O) 2 C 1 6 alkyl; R 1 4 is hydrogen, C 1 6 alkyl or di(CIA alkyl)aminosulfonyl; R 6 is hydrogen, hydroxy, halo, C 1 6 alkyl, cyano, haloC 1 6 alkyl, hydroxyC- 1 6 alkyl, cyanoC 1 6 alkyl, aminoCI. 6 alkyl, C 1 6 alkyloxyC 1 6 alkyl, C 1 6 alkylthioC 1 6 alkyl, aminocarbonyl-CI. 6 alkyl, CI-6 alkyloxycarbonylC 1 6 alkyl, C 1 6 alkylcarbonylC 1 6 alkyl, C 1 6 alkyloxycarbonyl, mono- or di(CI- 6 alkyl)aminoCj. 6 alkyl, Ar 5 Ar 5 CI- 6 alkyloxyCj. 6 alkyl; or a radical of formula 1), or R 9 wherein R 7 is hydrogen, CI- 6 alkyl, C 1 6 alkylcarbonyl, Ar 6 Ar 6 C 1 6 alkyl, C 1 6 alkyloxycarbonylC 1 6 alkyl, or a radical of formula Alk--OR' 0 or Alk--NR' 1 R1 2 R 8is hydrogen, CI. 6 alkyl, Ar 7or Ar 7--C 1 6 alkyl; R 9 is hydrogen, C 1 6 alkyl, C 1 6 alkylcarbonyl, C 1 6 alkyloxycarbonyl, C 1 6 alkylaminocarbonyl, Ar 8, Ar 8-C 1 6 alkyl, C 1 6 alkylcarbonyl-CI- 6 alkyl, Ar 8 -carbonyl, Ar 8 C 1 6 alkylcarbonyl, aminocarbonylcarbonyl, C 1 6 alkyloxyC 1 6 alkylcarbonyl, hydroxy, C 1 6 alkyloxy, aminocarbonyl, di(CI- 6 alkyl)aminoC 1 6 alkylcarbonyl, amino, C 1 6 alkylamino, C 1 6 alkylcarbonylamino, or a radical or formula Alk--OR' 0 or Alk--NR 1 R 1 2 wherein Alk is C 1 6 alkanediyl; R1 0 is hydrogen, CI. 6 alkyl, CI-6 alkylcarbonyl, hydroxyCI- 6 alkyl, Ar 9 or Ar 9 C 1 6 al kyl; R" is hydrogen, C,- 6 alkyl, CI-6 alkylcarbonyl, Arlo or Arlo C.-6 alkyl; R' 2 is hydrogen, C,- 6 alkyl, Ar" or Ar" -C I alkyl; and O Arl to Ar1 are each independently selected from phenyl; or phenyl substituted with 00 halo, C,- 6 alkyl, CI- 6 alkyloxy or trifluoromethyl.
54. 76. The method according to claim 71, wherein the dotted line represents an optional bond; X is O or S; 2 IDR' and R are each independently selected from hydrogen, halo, CI-6 alkyl, C-6 0 10 alkyloxy, trihalomethyl or trihalomethoxy; R 3 and R 4 are each independently selected from hydrogen, halo, C,- 6 alkyl, C'-6 alkyloxy, trihalomethyl or trihalomethoxy; radical of formula wherein R' 3 is hydrogen or RS 5 is a radical of formula (d-2) wherein R13 is hydrogen or C,- 6 alkyl and R' 4 is hydrogen or C,- 6 alkyl; R 6 is hydrogen, hydroxy, haloC,. 6 alkyl, hydroxyCl- 6 alkyl, cyanoC,. 6 alkyl, C, 6 alkyloxycarbonylCl.-6 alkyl, or a radical of formula -NR 8 R 9 wherein R 8 is hydrogen or C-. 6 alkyl and R 9 is hydrogen, CI- 6 alkyl, C.I-6 alkyloxy or CI6 alkyloxyCl- 6 alkylcarbonyl.
55. 77. The method according to claim 75, wherein X is oxygen; the dotted line represents a bond; R' is 3-halo; R 2 is hydrogen; R 3 is 4-halo; R 4 is hydrogen; RS 5 a radical of formula wherein R' 3 is hydrogen or RS 5 is a radical of formula wherein R' 3 is hydrogen and R' 4 is C1-4 alkyl; R 6 is hydrogen, halo, hydroxy or amino; and is (a-2) or
56. 78. The method according to claim 75, wherein the compound is 7-(3-chlorophenyl)-9-[(4-chlorophenyl)- I H-imidazol- 1 -ylmethyl]-2,3-dihydro- I 7-(3-chlorophenyl)-9-[(4-chlorophenyl)-1 H-imidazol-I -ylmethyl]- 1,2-dihydro-4H- pyrrolo[3,2,-ij]quinoline-4-one; 8-[amino(4-chlorophenyl)( 1-methyl- 1H-imidazol-5-yl)methyl]-6-(3-chlorophenyl)-1,2- dihydro-4H-pyrrolo[3,2,1-ij]quinolin-4-one; or 8-[amino(4-chlorophenyl)( 1-methyl-i H-imidazol-5-yl)methyl]-6-(3 -chlorophenyl)-2,3- dihydro- 1 or a stereoisomeric form, or a pharmaceutically acceptable acid addition salt thereof.
57. 79. The method of claim 75, wherein the famesyl transferase inhibitor compound has the structure an acid addition salt or a stereochemically isomeric form thereof, wherein the dotted line represents an optional bond; wherein X, R 2 R 3 and R 4 are as defined in claim 61. The method of any of claims 75-79, wherein the effective amount comprises about of body weight to about 1000mg/kg of body weight at a frequency of administration from once a day to once a month.
58. 81. The method of claim 80, further comprising administering to the subject an amount of one or more non-farnesyl transferase inhibitor compounds effective to treat a neurological disorder.
59. 82. The method of claim 81, wherein each non-famesyl transferase inhibitor compound is selected from the group consisting of: dopamine agonist, DOPA decarboxylase inhibitor, dopamine precursor, monoamine oxidase blocker, cathechol 0-methyl transferase inhibitor, anticholinergic, and NMDA antagonist.
60. 83. An article of manufacture comprising packaging material and a farnesyl transferase inhibitor compound according to any of claims 75-79, wherein the article of ID manufacture further comprises a label or package insert indicating that the farnesyl transferase S inhibitor compound can be administered to a subject for treating a synucleinopathy. O O 00 84. The article of manufacture of claim 83, wherein the synucleinopathy is selected from the group consisting of: Parkinson's disease, diffuse Lewy body disease, and multiple system atrophy disorder. NO
61. 85. The article of manufacture of claim 84, further comprising one or more non- IN farnesyl transferase inhibitor compounds effective to treat a neurological disorder. S
62. 86. The article of manufacture of claim 85, wherein each non-farnesyl transferase inhibitor compound is selected from the group consisting of: dopamine agonist, DOPA decarboxylase inhibitor, dopamine precursor, monoamine oxidase blocker, cathechol 0-methyl transferase inhibitor, anticholinergic, and NMDA antagonist.
63. 87. A method of treating a synucleinopathic subject, the method comprising, administering to a synucleinopathic subject a farnesyl transferase inhibitor of formula: or 258 R 3 R 16 (11) or (111) or a stereoisomeric form, or a pharmaceutically acceptable acid or base addition salt form thereof, in a therapeutically effective amount, wherein the dotted line represents an optional bond; X is oxygen or sulfur; R' is hydrogen, CI- 1 2 alkyl, Arl, Ar 2 C 1 6 alkyl, quinolinylC 1 6 alkyl, pyridylC 1 -6 alkyl, hydroxyCI. 6 alkyl, C 1 6 alkyloxyCI- 6 alkyl, mono- or di (C 1 6 alkyl) aminoC 1 6 alkyl, aminoC 1 6 alkyl, or a radical of formula -Alk' -Alk' or -Alk 1 -S (0)2- R wherein Alk' is C,. 6 alkanediyl, 259 IN9 R9 is hydroxy, C 1 6 alkyl, C 1 6 alkyloxy, amino, C 1 8 alkylamino or Ci. 8 alkylamino substituted with C 1 6 aikyloxycarbonyl; oR 2, R 3and R 16each independently are hydrogen, hydroxy, halo, cyano, CI- 6 alkyl, C 1 6 00 aikyloxy, hydroxyCI- 6 alkyloxy, C 1 6 alkyloxyC 1 6 alkyloxy, aminoCI 1 6 alkyloxy, mono- or di(Cj. 6 alkyl)aminoC 1 6 alkyloxy, Ar 1 Ar 2 C 1 6 alkyl, Ar 2 oxy, Ar 2 C 1 6 alkyloxy, hydroxycarbonyl, C 1 -6 alkyloxycarbonyl, trihalomethyl, trihalomethoxy, C 2 6 alkenyl, 4,4- dimethyloxazolyl; or 2 3 when on adjacent positions R and R 3 taken together may form a bivalent radical of formula -0-CH 2 (a-I1), -0-CH 2 -CH 2 (a-2) -0-CH=CH- (a-3) -0-CH 2 -CH 2 (a-4) -0-CH 2 -CH 2 -CH 2 or -CH=CH-CH=CH- R 4 and R 5 each independently are hydrogen, halo, Arl, C 1 6 alkyl, hydroxyCi- 6 alkyl, C 1 6 alkyloxyC 1 6 alkyl, C 1 6 alkyloxy, C 1 6 alkylthio, amino, hydroxycarbonyl, C 1 6 alkyloxycarbonyl, C 1 6 alkylS C 1 6 alkyl or C 1 6 alkyiS (0)2 C 1 6 alkyl; R 6 and R 7 each independently are hydrogen, halo, cyano, C 1 6 alkyl, C 1 6 alkyloxy, Ar 2 oxy, trihalomethyl, C 1 6 alkylthio, di (C 1 6 alkyl) amino, or when on adjacent positions R 6 and R 7 taken together may form a bivalent radical of formula -0-CH 2 or -CH=CH-CH=CH- R 8is hydrogen, C 1 6 alkyl, cyano, hydroxycarbonyl, C 1 6 alkyloxycarboriyl, C 1 6 alkylcarbonylC 1 6 alkyl, cyanocCI- 6 alkyl, C 1 6 alkyloxycarbonylC. 6 alkyl, carboxyCI- 6 alkyl, hydroxyC 1 6 alkyl, aminoC 1 6 alkyl, mono- or di (C 1 6 alkyl)-aminoC 1 6 alkyl, imidazolyl, haloC 1 6 alkyl, CI-6 alkyloxy-C 1 6 alkyl, aminocarbonylC 1 6 alkyl, or a radical of formula -O-R10(b-i1), -S-R10(b-2), -N-R 1 1 R 1 2 wherein R1 0 is hydrogen, C 1 6 alkyl, C 1 6 alkylcarbonyl, Ar 1 Ar 2 C 1 6 alkyl, CI- 6 alkyloxycarboriylCl.6 alkyl, a radical or formula -Alk 2 -OR 1 3 or -Alk 2 -NR 14 R" R 1 1 is hydrogen, C 1 12 alkyl, Ar 1 or Ar 2 C 1 6 al kyl; \12 R12 is hydrogen, C,- 6 alkyl, C- 6 alkylcarbonyl, C.I- 6 alkyloxycarbonyl, C.I-6 1 2 alkylaminocarbonyl, Ar', Ar Cl-6 alkyl, CI- 6 alkylcarbonylCl-6 alkyl, a natural O amino acid, Ar' carbonyl, Ar 2 CI-6 alkylcarbonyl, amninocarbonylcarbonyl, Ci-6 00 alkyloxyC, 6 alkyl-carbonyl, hydroxy, CI-6 alkyloxy, aminocarbonyl, di(C,-6 alkyl)aminoC- 6 alkylcarbonyl, amino, CI- 6 alkylamino, alkylcarbonylamino, or a radical of formula -Alk 2 -OR' 3 or -Alk 2 -NR' 4 R' wherein Alk 2 is CI- 6 alkanediyl; 13 2 R is hydrogen, CI- 6 alkyl, C.I- 6 alkylcarbonyl, hydroxyC 6 alkyl, Arl or Ar O 10 CI- 6 alkyl; R' 4 is hydrogen, C.I-6 alkyl, Ar' or Ar 2 CI- 6 alkyl; R' 5 is hydrogen, C.I-6 alkyl, C,- 6 alkylcarbonyl, Ar' or Ar2 CI- 6 alkyl; R' 7 is hydrogen, halo, cyano, CI- 6 alkyl, CI- 6 -alkyloxycarbonyl, Ar' R' 8 is hydrogen, CI- 6 alkyl, CI- 6 alkyloxy or halo; RI 9 is hydrogen or CI- 6 alkyl; Ar is phenyl or phenyl substituted with CI- 6 alkyl, hydroxy, amino, CI-,. 6 alkyloxy or halo; and Ar 2 is phenyl or phenyl substituted with CI- 6 alkyl, hydroxy, amino, CI-6 alkyloxy or halo.
64. 88. The method of claim 87, wherein the farnesyl transferase inhibitor is a compound of formula and wherein X is oxygen.
65. 89. The method of claim 87, wherein the farnesyl transferase inhibitor is a compound of formula and wherein the dotted line represents a bond.
66. 90. The method of claim 87, wherein the farnesyl protein transferase inhibitor is a compound of formula and wherein R' is hydrogen, CI- 6 alkyl, C,. 6 alkyloxyC. 6 alkyl or mono- or di (CI- 6 alkyl)aminoCl-6 alkyl.
67. 91. The method of claim 87, wherein the farnesyl protein transferase inhibitor is a compound of formula and wherein R 3 is hydrogen and R 2 is halo, C,. 6 alkyl, C 2 6 alkenyl, C,- 6 alkyloxy, trihalomethoxy or hydroxryC,. 6 alkyloxy.
68. 92. The method of claim 78, wherein the farnesyl protein transferase inhibitor is a compound of formula and wherein R 8 is hydrogen, hydroxy, haloC.s 6 alky, hydroxyC 6 alkyl, cyanoC,- 6 alkyl, C,- 6 alkyloxycarbonylCl- 6 alkyl, imidazolyl, or a radical of formula NR" R2 wherein R" is hydrogen or CI-1 2 alkyl and R1 2 is hydrogen, CI- 6 alkyl, C,-6 alkyloxy, C-6 alkyloxyCl-6 alkylcarbonyl, hydroxy, or a radical of formula -Alk 2 -OR' 3 00 wherein R' 3 is hydrogen or C,- 6 alkyl.
69. 93. The method of claim 87, wherein the compound is 4-(3-chlorophenyl)-6-[(4- chlorophenyl)hydroxy( 1-methyl-i H-imidazol-5-yl)methyl]- 1 -methyl-2(1 H)-quinolinone, 6- [amino(4-chlorophenyl)- 1-methyl-i H-imidazol-5-ylmethyl]-4-(3-chlorophenyl)- 1-methyl- IN 2(1H)-quinolinone; 6-[(4-chlorophenyl)hydroxy( I-methyl-i H-imidazol-5-yl)methyl]-4-(3- O 10 ethoxy-phenyl)- 1 -methyl-2(1 H)-quinolinone; 6-[(4-chlorophenyl)(1-methyl-i yl)methyl]-4-(3-ethoxyphenyl)- I1-methyl-2(1 H)-quinolinone monohydrochloride.monohydrate; 6-[amino(4-chlorophenyl)( 1-methyl-i yl)methyl]-4-(3-ethoxyphenyl)- 1 -methyl-2(1 H)-quinolinone, and 6-amino(4- chlorophenyl)(1 -methyl-i H-imidazol-5-yl)methyl]-1-methyl-4-(3-propylphenyl)-2(1H quinolinone; or a stereoisomeric form thereof, or a pharmaceutically acceptable acid or base addition salt thereof.
70. 94. The method of claim 87, wherein the compound is (+)-6-[amino(4- chlorophenyl)(1 -methyl-i H-imidazol-5-yl)methyl]-4-(3-chloro-phenyl)- I -methyl-2(1 H)- quinolinone; or a pharmaceutically acceptable acid addition salt thereof. The method of any one of claims 87-94, wherein the effective amount comprises about IOng/kg of body weight to about 1000mg/kg of body weight at a frequency of administration from once a day to once a month.
71. 96. The method of claim 95, further comprising administering to the subject an amount of one or more non-farnesyl transferase inhibitor compounds effective to treat a neurological disorder.
72. 97. The method of claim 96, wherein each non-farnesyl transferase inhibitor compound is selected from the group consisting of: dopamine agonist, DOPA decarboxylase inhibitor, dopamine precursor, monoamine oxidase blocker, cathechol 0-methyl transferase inhibitor, anticholinergic, and NMDA antagonist. t"- O S 10 (-N ¢-q
73. 98. An article of manufacture comprising packaging material and a famesyl transferase inhibitor compound according to any one of claims 87-94, wherein the article of manufacture further comprises a label or package insert indicating that the faresyl transferase inhibitor compound can be administered to a subject for treating a synucleinopathy.
74. 99. The article of manufacture of claim 98, wherein the synucleinopathy is selected from the group consisting of: Parkinson's disease, diffuse Lewy body disease, and multiple system atrophy disorder.
75. 100. The article of manufacture of claim 99, further comprising one or more non- farnesyl transferase inhibitor compounds effective to treat a neurological disorder.
76. 101. The article of manufacture of claim 100, wherein each non-farnesyl transferase inhibitor compound is selected from the group consisting of: dopamine agonist, DOPA decarboxylase inhibitor, dopamine precursor, monoamine oxidase blocker, cathechol 0-methyl transferase inhibitor, anticholinergic, and NMDA antagonist.
77. 102. A method of treating a synucleinopathic subject, the method comprising, administering to a synucleinopathic subject a farnesyl transferase inhibitor of formula: or a stereoisomeric form, or a pharmaceutically acceptable acid or base addition salt form thereof, in a therapeutically effective amount, wherein =X'-X 2 -X 3 is a trivalent radical of formula o=N-CR 6=CR 7- (X-1)I 00 =N-N=CR 6 =N-CR 6 6_ 7 =CR -CR =CR 6 7_ ID=CR -N=CR =CR or =CR 6 wherein each R 6, R 7and R 8 are independently hydrogen, C 14 alkyl, hydroxy, C 1 alkyloxy, aryloxy, C 14 alkyloxycarbonyl, hydroxyCI- 6 alkyl, C 14 alkyloxyC 1 4 alkyl, mono- or di(CI- 6 alkyl)aminoC 14 alkyl, cyano, amino, thio, C,. 4 alkylthio, arylthio or aryl; >Yl _y 2 is a trivalent radical of formula >CH-CHR 9 (y-l1), >CH-NR 9 or wherein each R 9 independently is hydrogen, halo, halocarbonyl, aminocarbonyl, hydroxyC 1 4 alkyl, cyano, carboxyl, C 14 alkyl, CI- 4 alkyloxy, C 14 alkyloxyCI 4 alkyl, C 14 alkyloxycarbonyl, mono- or di(CI- 6 alkyl)amino, mono- or di(C 14 alkyl)aminoC 14 alkyl, or aryl; r and s are each independently 0, 1, 2, 3, 4 or t is0, 1, 2or 3; each R1 and R 2 are independently hydroxy, halo, cyano, C 1 6 alkyl, trihalomethyl, trihalomethoxy, C 2 6 alkenyl, C 1 6 alkyloxy, hydroxyC 1 6 alkyloxy, C 1 6 alkylthio, C 1 6 alkyloxyC 1 6 alkyloxy, C 1 6 alkyloxycarbonyl, aminoC 1 6 alkyloxy, mono- or di(C 1- 6 alkyl)amino, mono- or di(CI- 6 alkyl)aminoC 1 6 alkyloxy, aryl, arYIC 1 6 alkyl, aryloxy or arylC 1 6 alkyloxy, hydroxycarbonyl, CI- 6 alkyloxycarbonyl, aminocarbonyl, aminoC 1 6 alkyl, mono- or di(C 1- 6 alkyl)aminocarbonyl, or mono- or di(C 1. 6 alkyl)aminoC 1 6 alkyl; or two R' or R 2 substituents adjacent to one another on the phenyl ring independently form together a bivalent radical of formula -O-CH 2 -O-CH 2 -CH 2 o-O=CH=CH- 00 -O-CH 2 -CH 2 -O-CH 2 -CH 2 -CH 2 or -CH=CH-CH=CH- R 3 is hydrogen, halo, C 1 6 alkyl, cyano, haloC 1 6 alkyl, hydroxyC 1 6 alkyl, cyanoCI. 6 alkyl, aminoC 1 6 alkyl, CI- 6 alkyloxyCi.6 alkyl, C 1 6 alkyithioC 1.6 alkyl, aminocarbonyl, C 1 .6 alkyl, hydroxycarbonyl, hydroxycarbonylC 1 6 alkyl, C 1 6 alkyloxycarbonylC 1 6 alkyl, C 1 6 C) 10 alkylcarbonylC 1 6 alkyl, C 1 6 alkyloxycarbonyl, aryl, arylCI- 6 alkyloxyCi 6alkyl, mono- or di(CI. 6 alkyl)aminoC 1 6 alkyl; or a radical of formula or -NR1R 12(b-3), wherein R1 0 is hydrogen, C 1 6 alkyl, C 1 6 alkylcarbonyl, aryl, arylC 1 6 alkyl, CI. 6 alkyloxycarbonyl C 1 6 alkyl, or a radical of formula -Alk--OR' 3 or -Alk--NR' 4 R1 5 R" is hydrogen, C 1 6 alkyl, aryl or arylC.. 6 alkyl; R 1 2 is hydrogen, C 1 6 alkyl, aryl, hydroxy, amino, C 1 6 alkyloxy, C 1 6 alkylcarbonylC 1 6 alkyl, arylC 1 6 alkyl, C 1 6 alkylcarbonylamino, mono- or di(CI- 6 alkyl)amnino, C 1 6 alkylcarbonyl, aminocarbonyl, arylcarbonyl, haloC 1 6 alkylcarbonyl, arylC 1 6 alkylcarbonyl, C 1 6 alkyloxycarbonyl, C 1 6 alkyloxyC 1 6 alkylcarbonyl, mono- or di(C 1- 6 alkyl)aminocarbonyl wherein the alkyl moiety may optionally be substituted by one or more substituents independently selected from aryl or C 1 3 alkyloxycarbonyl, aminocarbonylcarbonyl, mono- or di(CI- 6 alkyl)aminoC 1 6 alkylcarbonyl, or a radical of formula -Alk--OR 1 3 or -Alk--NR' 4 R" wherein Alk is C 1 6 alkanediyl; R 1 3 is hydrogen, C 1 6 alkyl, C 1 6 alkylcarbonyl, hydroxyC 1 6 alkyl, aryl or arylC 1. 6 alkyl; R 1 4 is hydrogen, C 1 6 alkyl, aryl or arylC 1 6 alkyl; R 1 5 is hydrogen, C 1 6 alkyl, CI- 6 alkylcarbonyl, aryl or arylC 1 6 alkyl; R 4 is aradical of formula N R 16 (c-I) N "16 00 N R1 (c-2) wherein R 1 6 is hydrogen, halo, aryl, C 1 6 alkyl, hydroxyCI- 6 alkyl, C 1 6 alkyloxyCI-6 NO alkyl, C 1 6 alkyloxy, CI- 6 alkylthio, amino, mono- or di(C 1 4 alkyl)amino, hydroxycarbonyl, N 5 C 1 6 alkyloxycarbonyl, C 1 6 alkylthioC 1 6 alkyl, C 1 6 alkylS(O)C 1 6 alkyl or C 1 6 alkylS(O) 2 C 1 6 alkyl; R 1is hydrogen, C 1 6 alkyl, C 1 6 alkyloxyC 1 6 alkyl, arylCI. 6 alkyl, trifluoromethyl or di(CI4 alkyl)aminosulfonyl; R 5 is C 1 6 alkyl C 1 6 alkyloxy or halo; aryl is phenyl, naphthalenyl or phenyl substituted with one or more substituents each independently selected from halo, C 1 6 alkyl, C 1 6 alkyloxy or trifluoromethyl; with the proviso that that when R, 6 is bound to one of the nitrogen atoms in the imidazole ring of formula or R 16 is hydrogen, aryl, C 1 6 alkyl, hydroxyCI- 6 alkyl, C 1 6 alkyloxyCI. 6 alkyl, C 1 6 alkyloxycarbonyl, C 1 6 alkylS(O)CI- 6 alkyl or C 1 6 alkyIS(O) 2 C 1 6 alkyl.
78. 103. The method according to claim 102, wherein each R1 and R 2 are independently hydroxy, halo, cyano, C 1 6 alkyl, trihalomethyl, trihalomethoxy, C 2 6 alkenyl, C 1 6 alkyloxy, hydroxyCI- 6 alkyloxy, C 1 6 alkylthio, CI. 6 alkyloxyC 1 6 alkyloxy, C 1 6 alkyloxycarbonyl, aminoC 1 6 alkyloxy, mono- or di(C 1. 6 alkyl)amino, mono- or di(C 1- 6 alkyI)aminoC 1 alkyloxy, aryl, arylC 1 6 alkyl, aryloxy or arylC 1 6 alkyloxy, hydroxycarbonyl, or C 1 6 alkyloxycarbonyl; or two R' or R 2substituents adjacent to one another on the phenyl ring independently form together a bivalent radical of formula -O-CH 2 (a-i1), -O-CH 2 -CH 2 -O=CH=CH- -O-CH 2 -CH 2 -O-CH 2 -CH 2 -CH 2 or -CH=CH-CH=CH- R 1 7 is hydrogen, C 1 6 alkyl, trifluoromethyl or di(CI- 6 alkyl)aminosulfonyl; ID O with the proviso that that when R 16 is bound to one of the nitrogen atoms in the imidazole ring of formula R 1 6 is hydrogen, aryl, CI- 6 alkyl, hydroxyCi6 alkyl, CI-6 SalkyloxyCi- 6 alkyl, CI- 6 alkyloxycarbonyl, CI- 6 alkylS(O)C 1 6 alkyl or Ci- 6 alkylS(O) 2 CI-6 00 alkyl.
79. 104. The method according to claim 102, wherein X 2 X 3 is a trivalent radical of formula or wherein each R 6 independently is hydrogen, Ci. 4 alkyl, CI- 6 alkyloxycarbonyl, amino or aryl and R 7 is hydrogen; 2 is a trivalent \D radical of formula or wherein each R 9 independently is hydrogen, 0 0 halo, carboxyl, C1-4 alkyl or CI-4 alkyloxycarbonyl; r is 0, 1 or 2; s is 0 or 1; t is 0; R' is halo, CI- 6 alkyl or two R' substituents ortho to one another on the phenyl ring independently form together a bivalent radical of formula R 2 is halo; R 3 is halo or a radical of formula or wherein R' 1 is hydrogen or a radical of formula -Alk- OR' 3 R" is hydrogen, R 1 2 is hydrogen, Ci. 6 alkyl, C.-6 alkylcarbonyl, hydroxy, Ci. 6 alkyloxy or mono- or di(Ci. 6 alkyl)aminoCi. 6 alkylcarbonyl, Alk is CI- 6 alkanediyl and R 1 3 is hydrogen; R 4 is a radical of formula or wherein R 16 is hydrogen, halo or mono- or di(Ci-4 alkyl)amino; R 17 is hydrogen or CI- 6 alkyl; aryl is phenyl.
80. 105. The method according to claim 102, wherein X 2 X 3 is a trivalent radical of formula __y2 is a trivalent radical of formula r is 0 or 1, s is 1, t is 0, R3 is 3-chloro, R 2 is 4-chloro or 4-fluoro, R 3 is hydrogen or a radical of formula or R 4 is a radical of formula or R 6 is hydrogen, R 7 is hydrogen, R 9 is hydrogen, R 1 0 is hydrogen, R 11 is hydrogen and R 1 2 is hydrogen.
81. 106. The method according to claim 102, wherein X 2 -X 3 is a trivalent radical of formula or Y 2 is a trivalent radical of formula or r and s are 1, t is 0, R' is 3-chloro or 3-methyl, R 2 is 4-chloro, R 3 is a radical of formula (b-1) or R 4 is a radical of formula R 6 is C-4 alkyl, R 9 is hydrogen, R 1 0 and R" are hydrogen and R 1 2 is hydrogen or hydroxy.
82. 107. The method according to claim 102, wherein the famesyl transferase inhibiting compound is selected from: 7-[(4-fluorophenyl)(1H-imidazol- -yl)methyl]-5-phenylimidazo [1,2-a]quinoline; a-(4- chlorophenyl)-.alpha.-( 1-methyl-I H-imidazol-5-yl)-5-phenylimidazo[1,2-a]quinoline-7- methanol; 5 -chlorophenyl)-. alpha. -(4-chlorophenyl)-. alpha. -methylI-I H-i midazol-5 yl)-imidazol [1 ,2-a]quinoline-7-methanol; 5 -chlorophenyl)-ct-(4-ch lorophenyl)-. alpha. 1- C.) 00(4-chlorophenyl)-a-( 1-methyl-i H-imidazol-5-yl)tetrazolo[1I,5-a]quinoline-7-methanamine; 5 -chilorophenyl)-ct-(4-chlorophenyl)- 1 -methyl 1-methyl -I H-imidazol1-5 1,2,4- triazoio[4,3-a]quinoline-7-methanol; 5-(3-chlorophenyl)-at-(4-chlorophenyl)-a-(I -methyl- 1 H-imidazol-5-yl)tetrazolo[ 1,5-a]quinoline-7-methanamine; 5-(3-chlorophenyl)-.a-(4- chlorophenyl)-a-( 1-methyl-I H-imidazol-5-yl)tetrazolo[ 1,5-a]quinazoline-7-methanoi; 5-(3- INDchlorophenyl)-a-(4-chlorophenyl)-4,5-dihydro-a-( 1-methyl-I H-imidazol-5-yl)tetrazolo[ C) 10 a]quinazoline-7-methanol; 5-(3-chlorophenyl)-a-(4-chiorophenyl)-a-( 1-methyl- I H- 1,5-a]quinazoline-7-methanamine; 5-(3-chlorophenyl)-a-(4- chloropheny)-N-hydroxy-x-( 1-methyl-i H-imidazol-5-yl)tetrahydro [1 ,5-a]quinoline-7- methanamine; a-(4-chlorophenyl)-a-(1 -methyl- I H-imidazol-5-yI)-5-(3- methylphenyl)tetrazoio[1I,5-a]quinoline-7-methanamine; a pharmaceutically acceptable acid addition salt and a stereochemically isomeric form thereof.
83. 108. The method of any of claims 102-107, wherein the effective amount comprises about 1 Ong/kg of body weight to about 1 000mg/kg of body weight at a frequency of administration from once a day to once a month.
84. 109. The method of claim 107, further comprising administering to the subject an amount of one or more non-famnesyl transferase inhibitor compounds effective to treat a neurological disorder. .110. The method of claim 109, wherein each non-farnesyl transferase inhibitor compound is selected from the group consisting of: dopamine agonist, DOPA decarboxylase inhibitor, dopamine precursor, monoamine oxidase blocker, cathechol 0-methyl transferase inhibitor, anticholinergic, and NMDA antagonist.
85. 111. An article of manufacture comprising packaging material and a famnesyl transferase inhibitor compound according to any of claims 88-93, wherein the article of manufacture further comprises a label or package insert indicating that the farnesyl transferase inhibitor compound can be administered to a subject for treating a synucleinopathy. IO
86. 112. The article of manufacture of claim 111, wherein the synucleinopathy is selected from the group consisting of: Parkinson's disease, diffuse Lewy body disease, and multiple O system atrophy disorder. 00
87. 113. The article of manufacture of claim 112, further comprising one or more non- farnesyl transferase inhibitor compounds effective to treat a neurological disorder. NO Cr 114. The article of manufacture of claim 113, wherein each non-farnesyl transferase IN0 inhibitor compound is selected from the group consisting of: dopamine agonist, DOPA 0 10 decarboxylase inhibitor, dopamine precursor, monoamine oxidase blocker, cathechol 0-methyl transferase inhibitor, anticholinergic, and NMDA antagonist.
88. 115. A method of treating a synucleinopathic subject, the method comprising, administering to a synucleinopathic subject a farnesyl transferase inhibitor of formula: R 3 R2 5 N 4 R 8 AN. R 1 R' or a stereoisomeric form, or a pharmaceutically acceptable acid or base addition salt form thereof, in a therapeutically effective amount, wherein the dotted line represents an optional bond; X is oxygen or sulfur; R' is hydrogen, CI-1 2 alkyl, Ar', Ar 2 CI- 6 alkyl, quinolinylC 1 _6 alkyl, pyridylCi-6 alkyl, hydroxyCi-6 alkyl, C 1 6 alkyloxyCI-6 alkyl, mono- or di(Ci-6 alkyl)aminoC 1 -6 alkyl, aminoCi. 6 alkyl, or a radical of formula -Alk'-C(=O)-R 9 -Alk'-S(O)-R 9 or -Alk'-S(0) 2 -R 9 wherein Alk' is C,. 6 alkanediyl, __R 9 is hydroxy, C,1- 6 alkyl, C,1- 6 alkyloxy, amino, C 1 8 alkylamino or C,1. 8 alkylamino C.) 00 R 2 and R 3 each independently are hydrogen, hydroxy, halo, cyano, CI- 6 alkyl, CI- 6 alkyloxy, hydroxyC 1- 6 alkyloxy, C 1 6 alkyloxyC 1 6 alkyloxy, aminoC 1 6 alkyloxy, mono- or di(C 1 6 alkyl)aminoC 1 6 alkyloxy, Ar', Ar 2 C,.6 alkyl, Ar 2 oxy, Ar 2 C,.6 alkyloxy, hydroxycarbonyl, C,. 6 alkyloxycarbonyl, trihalomethyl, trihalomethoxy, C 2 6 alkenyl; or when on adjacent positions R 2 and R 3 taken together may form a bivalent radical of formula IND -O-CH 2 I), -O-CH 2 -CH 2 -O-CH=CH- -O-CH 2 -CH 2 -O-CH 2 -CH 2 -CH 2 -CH=CH-CH=CH- R 4 and R 5 each independently are hydrogen, Ar', C,. 6 alkyl, C,. 6 alkyloxyC 1 6 alkyl, C,. 6 alkyloxy, C,. 6 alkylthio, amino, hydroxycarbonyl, C,. 6 alkyloxycarbonyl, C 1 6 alkylS(O)CI- 6 alkyl or C,. 6 alkylS(O) 2 C,. 6 alkyl; R 6 and R 7 each independently are hydrogen, halo, cyano, CI. 6 alkyl, C 1 6 alkyloxy or Ar 2 oxy; R 8 is hydrogen, C,. 6 alkyl, cyano, hydroxycarbonyl, C,.6 alkyloxycarbonyl, C,. 6 alkylcarbonyiC alkyl, cyanoC .6 alkyl, C I.6 alkyloxycarbonylCi -6 alkyl, hydroxycarbonylC,1. 6 alkyl, hydroxyC 1 6 alkyl, aminoC,1-6 alkyl, mono- or di(C 1 6 alkyl)aminoC,. 6 alkyl, haloC,. 6 alkyl, C 1 6 alkyloxyC,. 6 alkyl, aminocarbonylC. 6 alkyl, Arl, Ar 2C,. 6 alkyloxyC,. 6 alkyl, C,. 6 alkylthioC,. 6 alkyl; R1 0 is hydrogen, C 1 6 alkyl, C,. 6 alkyloxy or halo; R 11is hydrogen or C,1. 6 alkyl; Arl is phenyl or phenyl substituted with C 1 6 alkyl, hydroxy, amino, C,. 6 alkyloxy or halo; and Ar 2 is phenyl or phenyl substituted with C,. 6 alkyl, hydroxy, amino, C,. 6 alkyloxy or halo.
89. 116. The method of claim 115, wherein X is oxygen.
90. 117. The method of claim 115, wherein R' is hydrogen, 6 alkyl or 6 alkyloxyC,1 6 alkyl. o118. The method of claim 115, wherein R 6is hydrogen and R 7is halo. 00 119 The ethodof claim 115, wherein R 8 is hydrogen, C 1 6 alkyl or hydroxy-C 1 6 alkyl.
91. 120. The method of claim 115, wherein the compound is IND 4-(3 -chlorophenyl)-6- [(4-chlorophenyl)- 1 H-imidazol- 1 -ylmethyl]- 1 -methyl-2( 1 H)- quinolinone; 4-(3 -chlorophenyl)-6- [(4-chlorophenyl)- 1 H-imidazol- 1 -ylmethyl] -2(l1 H)-qui nol inone; 6- [1 -(4-chlorophenyl)-2-hydroxy- 1 H-imidazol- 1 -yl)ethyl] 1 -methyl-4-phenyl-2( 1 H)- quinolinone; 4-(3 -chlorophenyl)-6- [1I-(4-chiorophenyl)- 1 H-imidazol- 1 -yl)ethyl] 1 -mehtyl-2( 1)- quinolinone; 4-(3 -chlorophenyl)-6- [1 -(4-chlorophenyl)- 1 -methyl- I H-imidazol- 1 -yl)ethyl] 1 -methyl- 2(1 H)-quinolinone; 4-(3-chlorophenyl)-6-[ 1-(4-chlorophenyl)-2-hydroxy- 1 H-imidazol- 1 -yl)ethyl]- 1 -methyl- 2(1 H)-quinolinone; 4-(3-chlorophenyl)-6-[(4-chlorophenyl)( 1 H-imidazol- 1 -yl)methyl]- 1 -(2-methoxyethyl)- 2(1 H)-quinolinone ethanedioate monohydrate; 6-[(4-chlorophenyl)( 1 H-imidazol- 1 -yl)methyl]-4-( 1,3-benzodioxol-5-yl)- I -methyl-2( I H)- quinolinone ethanedioate 1); or a stereoisomeric form thereof, or a pharmaceutically acceptable acid or base addition salt thereof.
92. 121. A method of treating a synucleinopathic subject, the method comprising, administering to a synucleinopathic subject a famesyl transferase inhibitor of formula: or a stereoisomeric form, or a pharmaceutically acceptable acid or base addition salt form thereof, in a therapeutically effective amount, wherein the radicals R 2 R 3 R4, Rs, R6, R 7 Rs, RIO and R I are as defined in claim 4, or a pharmaceutically acceptable acid addition salt thereof.
93. 122. A method of treating a synucleinopathic subject, the method comprising, administering to a synucleinopathic subject a farnesyl transferase inhibitor of formula: O or a stereoisomeric form, or a pharmaceutically acceptable acid or base addition salt form thereof, in a therapeutically effective amount, wherein the radicals R2, R 3 R 4 Rs, R6, R7, Rs, Rio and RI, are as defined in claim 4, or a pharmaceutically acceptable acid addition salt thereof.
94. 123. The method of any one of claims 115-122, wherein the effective amount ID comprises about 1 Ong/kg of body weight to about 1000mg/kg of body weight at a frequency of administration from once a day to once a month. C) O oO 124. The method of claim 123, further comprising administering to the subject an amount of one or more non-farnesyl transferase inhibitor compounds effective to treat a neurological disorder. O S125. The method of claim 124, wherein each non-farnesyl transferase inhibitor I\O compound is selected from the group consisting of: dopamine agonist, DOPA decarboxylase 0 10 inhibitor, dopamine precursor, monoamine oxidase blocker, cathechol 0-methyl transferase inhibitor, anticholinergic, and NMDA antagonist.
95. 126. An article of manufacture comprising packaging material and a farnesyl transferase inhibitor compound according to any one of claims 115-122, wherein the article of manufacture further comprises a label or package insert indicating that the farnesyl transferase inhibitor compound can be administered to a subject for treating a synucleinopathy.
96. 127. The article of manufacture of claim 126, wherein the synucleinopathy is selected from the group consisting of: Parkinson's disease, diffuse Lewy body disease, and multiple system atrophy disorder.
97. 128. The article of manufacture of claim 127, further comprising one or more non- farnesyl transferase inhibitor compounds effective to treat a neurological disorder.
98. 129. The article of manufacture of claim 128, wherein each non-farnesyl transferase inhibitor compound is selected from the group consisting of: dopamine agonist, DOPA decarboxylase inhibitor, dopamine precursor, monoamine oxidase blocker, cathechol 0-methyl transferase inhibitor, anticholinergic, and NMDA antagonist.
99. 130. A method of treating a synucleinopathic subject, the method comprising, administering to a synucleinopathic subject a farnesyl transferase inhibitor compound of the formula: 273 R 4 R INDB R 4 R C.) 00 N R 8 N NO W 0 NRrSs-Tt v R, R 7 IV or a stereoisomeric form, or a pharmaceutically acceptable acid or base addition salt form thereof, in a therapeutically effective amount, wherein m,n,r,s and t are 0 or 1; p isO0, 1 or 2; V, W and X are selected from the group consisting of oxygen, hydrogen, R1, R 2 or R3 Z and Y are selected from the group consisting of CHR 9 So 2 So 3 CO, C0 2 0, NR'O 0, 2 II12 NR' ,CONR CN /CN N 0 N N-C -N-SO 2 -C R3 R14R 1 0 -0 2 S-jNrjJ 0v NR 20 R 21 N NR 22 R 16 R 17 ,R 18 R1 9 S S or Z may be absent; 6 7 0 12 13 14 15 16 1 20 21 22 24 25 26 7 R ,R R9R, R ,R R,R R R R'5,R R R',R' 9 R ,R 2 R ,R ,R ,R 26 R R 8 R29R 30 R 31 R 3 2 R 33, R 34, R 35, R 36, R 37 and R 38 are selected from the group consisting of hydrogen, lower alkyl, substituted alkyl, aryl, or substituted aryl; R 4 R 5 are selected from the group consisting of hydrogen, halo, nitro, cyano and U-R 23 U c is selected from the group consisting of sulfur, oxygen, NR 24 CO, SO, SO 2 CO 2 NR 2 o CO 2 NR 26 CONR 27 NR 28 S02, NR 2 S02 NR 30 SO 2 NR 31 NR 32 CO, CONR 3 3 PO2 R 34 00 and PO 3 R 35 or U is absent; R 2 and R 3 are selected from the group consisting of hydrogen, alkyl, alkoxycarbonyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, aralkyl, Scycloalkyl, aryl, substituted aryl, heterocyclo, substituted heterocyclo, cyano, carboxy, carbamyl CONH 2 or substituted carbamyl further selected from CONH alkyl, CONH \aryl, CONH aralkyl or cases where there are two substituents on the nitrogen selected from 0 10 alkyl, aryl or aralkyl; R and R 23 are selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, aralkyl, cycloalkyl, aryl, substituted aryl, heterocyclo, substituted heterocyclo; Any two of R 2 and R 3 can be joined to form a cycloalkyl group; R, S and T are selected from the group consisting of CH 2 CO and CH(CH 2 )pQ wherein Q is NR R 37 OR 38 or CN; and A, B, C and D are carbon, oxygen, sulfur or nitrogen. with the provisos that 1. When m is zero then V and W are not both oxygen or 2. W and X together can be oxygen only if Z is either absent, 0, NR' 0 CHR 9 O 11 -N-SO 2 R14 or R 1 in formulas I and II, and V and X together can be oxygen only if Y is O, NR' 1 CHR 9 0 -N-SO R14 or R1 in formulas III and IV or 3. R 23 may be hydrogen except when U is SO, SO2, NR 25 CO 2 or NR 28 SO 2 or 4. R 8 may be hydrogen except when Z is SO 2 CO 2 or 276 N-SO 2 0/N R 20 R 21 N NR 22
100. 131. The method of claim 130, wherein the famesyl transferase inhibitor compound is of the formula: R R 4 R R 2 R 3 R 4 R 1R 2 R 3 wherein m is 0; n is 1 and r, s and t are 0 or 1; p is0,lor 2; V, W and X are selected from the group consisting of oxygen, R 2 and R' ID SZ and Y are selected from the group consisting of CHR 9 SO2, SO 3 CO, CO 2 O, NR 1 0 SO2 NR", CONR 2 C) O 00 CN N O /C N II II N -N-SO 2 R 13 R14 0 O II S-C-N- N 0 NR20 R21N NR22 R 16 R 1 7 R 18 R 1 9 or Z may be absent; R 6 R 7 R 9 R 12 R 13 R 1 4 R15, R 16 R 17 R18, R 1 R 20 R21, R 22 R 24 R25, R 26 R27, R 2 8 R 2 9 R 0 R 3 2 R 3 R 34 R 35 R 36 R 37 and R 38 are selected from the group consisting of hydrogen, lower alkyl, substituted alkyl, aryl, or substituted aryl; R 4 and R 5 are selected from the group consisting of hydrogen, halo, nitro, cyano and U-R 23 U is selected from the group consisting of sulfur, oxygen, NR 24 CO, SO, SO 2 CO 2 NR 2 CO 2 NR 2 6 CONR 27 NR 28 SO 2 NR 29 SO2 NR 3 0 SO 2 NR 31 NR 32 CO, CONR 33 P0 2 R 34 and P0 3 R 35 or U is absent; R 2 and R 3 are selected from the group consisting of hydrogen, alkyl, alkoxycarbonyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, aralkyl, cycloalkyl, aryl, substituted aryl, hetercyclo, substituted heterocyclo, cyano, carboxy, carboxy, carbamyl or substituted carbamyl; R 8 and R 23 are selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, aralkyl, cycloalkyl, aryl, substituted aryl, heterocyclo and substituted heterocyclo; any two of R 2 and R 3 may be joined to form a cycloalkyl group; R, S, and T are selected from the group consisting of CH 2 CO and CH(CH 2 )pQ wherein Q is NR 36 R 37 OR 38 or CN; and A, B, C and D are carbon, with the provisos that 1. When m is zero then V and W are not both oxygen or 278 IND 0 2. W and X together can be oxygen only if Z is either absent, 0, NR", CHR', -N-C- 1 1 4 -N-SO 2 in formnula 11, and V and X together can be oxygen only if Y isO0, NR" 0 CHR', N j 1 1 -N-S 2 in formula IV or 3. R 23 may be hydrogen except when U is SO, SO 2 NR 2 1 CO 2 or NR 28 S02, or 4. R 8may be hydrogen except when Z is S02, C0 2 or -N-SO 2 0v NR 20 R 2 N NR 22
101. 132. The method of claim 130, wherein the compound is selected from the group consisting of: 2,3,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-4-( 1-naphthalenylcarbonyl)- I H- 1,4- benzodiazepine, hydrochloride; 8-Chloro-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-4-( 1 -naphthalenylcarbonyl)- I H- 1 ,4-benzodiazepine, hydrochloride; 2,3 ,4,5-Tetrahydro-4-( IH-imidazol-4-yl-methyl)- 1-(1-1 -naphthalenylcarbonyl)- 1 H- 1,4- benzodiazepine, dihydrochioride; 2,3 ,4,5-Tetrahydro-l1-(1 H-imidazol-4-yl-methyl)-2-methyl-4-( I-naphthalenylcarbonyl)- I-H- 1 ,4-benzodiazepine, hydrochloride; 2,3 ,4,5-Tetrahydro-4-( 1 -naphthalenylcarbonyl)- 1 -(phenylmethyl)- I yl]methyl] -IH-I ,4-benzodiazepine, hydrochloride; 2,3,4,5-Tetrahydro-( I H-imidazol-4-yl-methyl)-4-( I -naphthalenylsulfonyl)- I H- 1,4- benzodiazepine, hydrochloride; o ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-3-[2-(methylthio)ethyl]-4-(I 00 naphthalenylcarbonyl)- I H-I ,4-benzodiazepine, hydrochloride; 2,3,4,5-Tetrahydro- I H-imidazol-4-yl-methyl)-N-methyl-N-phenyl-4H- 1,4- benzodiazepine-4-carboxamide, hydrochloride; 2-[2,3 ,4,5-Tetrahydro- I H-imidazol-4-yl-methyl)- I H-i ,4-benzodiazepin-4- yl]sulfonyl]benzoic acid, methyl ester, hydrochloride; IND7-Bromo-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-4-( 1 -naphthalenylcarbonyl)- I H- 1 ,4-benzodiazepine, hydrochloride; 2,3,4,5-Tetrahydro- 1 I H-imidazol-4-ylmethyl)-4-( 1 -naphthalenenylcarbonyl)-7-phenyl- 1 H-i ,4-benzodiazepine, hydrochloride; 2,3,4,5-Tetrahydro- 1 H-imidazol-2-ylmethyl)-4-( 1 -naphthalenylcarbonyl)- 1 H- 1,4- benzodiazepine, dihydrochioride; 2,3,4,5-Tetrahydro- 1 1H-imidazol-2-yl)propyl]-4-( I -naphthalenylcarbonyl)- I H- 1,4- benzodiazepine, dihydrochioride; 1 -[3-Amino-3-( 1 H-imidazol-2-yI)propyl]-2,3,4,5-tetrahydro-4-( I -naphthalenylcarbonyl)- 1 H-i ,4-benzodiazepine, trihydrochioride; 2,3,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-3-methyl-4-( I -napthalenylcarbonyl)- I H- 1 ,4-benzodiazepine, hydrochloride; (S)-2,3,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-3-[2-(methylthio)ethyl]-4-( I naphthalenylmethyl)- I H-I ,4-benzodiazepine, hydrochloride; 2,3,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-9-methyl-4-( 1 -naphthalenylcarbonyl)- 1 H- 1 ,4-benzodiazepine, dihydrochloride; 2,3,4,5-Tetrahydro-4-( I H-imidazol-4-ylmethyl)-9-methyl-lI-(1 -naphthalenylcarbonyl)- 1 H- 1 ,4-benzodiazepine, dihyrdochioride; 1 -[[2-(2-Aminoethyl)- 1 H-imidazol-4-yl]methyl]-2,3 ,4,5-tetrahydro-4-( 1- naphthalenylcarbonyl)- 1 H-i ,4-benzodiazepine, trihydrochloride; I -[[2-Aminomethyl)- I H-imidazol-4-yllmethyl]-2,3 ,4,5-tetrahydro-4-( 1- naphthalenylcarbonyl)- I H-I ,4-benzodiazepine, trihydrochloride; N-[2,3 ,4,5-Tetrahydro-lI-(1 H-imidazol-4-ylmethyl)-4-( 1-naphthalenylcarbonyl)-lIH-i ,4- benzodiazepin-8-yl]acctamide, dihydrochloride; 2,3,4,5-Tetrahydro-l1-(1 H-i midazol-4-yl methyl)-4-( 1 -naphthal enyl carbony l)-8 -nitro- 1 H- 1,4- benzodiazepine, di hydrochloride; 2,3 ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-4-( 1 -naphthalenyl carbonyl)-8 -amino- 1 H- I ,4-benzodiazepine, dihydrochioride; o N-[2,3 ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-4-( I -naphthalenylcarbonyl)- I H- 1,4- 00 benzodiazepin-8-yl]benzamide, di hydrochloride; N-[2,3 ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-4-( I -naphthalenylcarbonyl)- 1 H- 1,4- benzodiazepin-8-yI]cyclohexanamide, dihydrochioride; 2,3 ,4,5-Tetrahydro- 1 H-imidazol-4-yl)ethyi]-4-( 1 -naphthalenylcarbonyl)- 1 H- 1,4- benzodiazepine, dihydrochioride; ID2,3 ,4,5-Tetrahydro- 1H-imidazol-4-yl)ethyl]-4-( 1-naphthalenylcarbonyl)-7-phenyl- 1H- C) 10 1 ,4-benzodiazepine, di hydrochloride; 7-Bromo-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-yI)ethyll-4-( 1 -naphthalenylcarbonyl)- 1 Hl- 1 ,4-benzodiazepine, d ihydrochloride; 1 -(2-Aminoethyl)- 1H-imidazol-5-yI]methyl]-2,3 ,4,5-tetrahydro-4-( 1- naphthalenylcarbonyl)-7-phenyl- I H-i ,4-benzodiazepine, trihydrochioride; 2,3 ,4,5-Tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-7-phenyl- I H-i ,4-benzodiazepine-4- carboxylic acid, phenylmethyl ester; 2,3 ,4,5-Tetrahydro-lI-(1 H-imidazol-4-ylmethyl)-7-phenyl-4-[2-(trifluoromethoxy)benzoyl]- 1 H-I ,4-benzodiazepine; 1,2,3 ,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-N-methyl-N,7-diphenyl-4H- 1,4- !0 benzodiazepine-4-carboxamide, dihydrochioride; 2,3 ,4,5,-Tetrahydro- 1 H-imidazol-4-ylmethyl)-4-( I -naphthaleneylcarbonyl)-7-( 1- piperidinylsulfonyl)- 1 H-i ,4-benzodiazepine, monohydrochioride; 2,3 ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-4-( I -naphthalenylcarbonyl)-7-pyridin-2-yl- 1 H-I ,4-benzodiazepine, trihydrochioride; 7-(2-Furanyl)-2,3,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-4-( I -naphthalenylcarbonyl)- 1 H-I ,4-benzodiazepine, di hydrochloride; 2,3 ,4,5-Tetrahydro- I H-imidazol-4-ylmethyl)-4-( I -naphthalenylcarbonyl)-7-(2-thienyl)- I H-I ,4-benzodiazepine, dihydrochloride; 2,3 ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-4-( 1 -naphthalenylcarbonyl)-7-(4- pyridinyl)- 1 H-i ,4-benzodiazepine, trihydrochioride; 2,3 ,4,5-Tetrahydro- 1 H-imidazol-2-yl)propyl]-4-( 1 -naphthalenylcarbonyl)-7-phenyl- 1 H-i ,4-benzodiazepine, dihydrochioride; 7-Bromo-2,3,4,5-tetrahydro-4-(1 H-imidazol-4-ylmethyl)- 1 -naphthalenylcarbonyl)- 1 H- 1 ,4-benzodiazepine, d ihydrochloride-, 8-Chloro-2,3 ,4,5-tetrahydro-4-( I H-imidazol-4-ylmethyl)- I -naphthalenylcarbonyl)- I H- 1 ,4-benzodiazepine, dihydrochioride; u 2,3 ,4,5-Tetrahydro-4-( 1 H-imidazol-4-ylmethyl)- 1 -naphthalenylcarbonyl)-7-phenyl- I H- 0I 1,4-benzodiazepine, hydrochloride; 2,3 ,4,5-Tetrahydro- 1 ,4-bis( 1 H-imidazol-4-ylmethyl)-7- phenyl- 1 H-i ,4-benzodiazepine, dihydrochioride; 2,3 ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-4-( 1-naphthalenylmethyl)-7-phenyl- I H- I ,4-benzodiazepine, tri fluoroacetate; 2,3 ,4,5-Tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-7-methoxy-4-( 1-naphthalenylcarbonyl)- IH- 1 ,4-benzodiazepine, dihydrochioride; C) 10 2,3,4,5-Tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-4-( 1 -naphthalenylcarbonyl)- 1 H- 1,4- benzodiazepine-7-carboxylic acid, dihydrochioride; 2,3 ,4,5-Tetrahydro- 1 H-imidazol-5-ylmethyl)-4-( 1 -naphthalenylcarbonyl)-7-cyclohexyl- I H-I ,4-benzodiazepine, 2.5 hydrochloride; 7-Butyl-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-4-( 1 -naphthalenylcarbonyl)- I H- 1,4- benzodiazepine, di hydrochloride; 1 -[[2-(2-Aminoethyl)- 1H-imidazol-4-yl]methyl]-2,3 ,4,5-tetrahydro-4-( 1- naphthalenylcarbonyl)-7-phenyl- I H-I ,4-benzodiazepine, trihydrochioride; 1 -[[2-(Aminomethyl)- IH-imidazol-4-yI]methyl]-2,3 ,4,5-tetrahydro-4-( 1- naphthalenylcarbonyl)-7-phenyl- 1 H-I ,4-benzodiazepine, trihydrochioride; 2,3 ,4,5-Tetrahydro-l1-( I H-imidazol-4-ylmethyl)-4-( I-naphthalenylcarbonyl)-8-[N,N- bis(phenyl-methyl)amino]- I H-I ,4-benzodiazepine, trihydrochioride; N-[2,3 ,4,5-Tetrahydro- 1 H-imidazol-4-yl-methyl)-4-( I -naphthalenylcarbonyl)- 1 H- 1,4- benzodiazepin-8-yl]phenylsulfonamide, dihydrochioride; N-Phenyl-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-yl-methyl)-4-( 1 -naphthalenylcarbonyl)- 1 H- 1 ,4-benzo-diazepine-7-carboxamide, dihydrochioride; N-[2,3 ,4,5-Tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-4-( I-naphthalenylcarbonyl)- 1 H- 1,4- benzodiazepin-8-yl]-3-methylbenzamide, dihydrochioride; N-[2,3 ,4,5-Tetrahydro-lI-(I H-imidazol-4-ylmethyl)-4-( 1-naphthalenylcarbonyl)- I H- 1,4- benzodiazepin-8-yl]-4-methylbenzarnide, di hydrochloride; 3-Chloro-N-[2,3 ,4,5-tetrahydro-l1-(1 H-imidazol-4-yI-methyl)-4-( 1-naphthalenylcarbonyl)- I H-i ,4-benzo-diazepin-8-yI]benzamide, dihydrochioride; 7-Bromo-2,3 ,4,5,-tetrahydro-l1-[[2-[(dimethylamino)-methyl]-l1H-imidazol-4-yllmethyl]-4- (I -naphthalenylcarbonyl)- 1 H- 1 ,4-benzodiazepine, dihydrochioride; 282 7-(4-Chlorophenyl -2,3,4,5-tetrahydro- 1 H-imidazoi-4-ylmethyi)-4-( 1- naphthalenylcarbonyl)- 1 H-i ,4-benzodiazepine, di hydrochloride; C.) 00 naphthalenylcarbonyl)- 1 H-i ,4-benzodiazepine, trihydrochioride; 1 -Methyl-N-[2,3,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-4-( 1 -naphthalerylcarbonyl)- 1 H-i ,4-benzodiazepin-8-yi]- 1 H-pyrrole-2-carboxamide, trihydrochioride; N-[2,3,4,5-Tetrahydro- I H-imidazol-4-ylmethyl)-4-( 1 -naphthalenylcarbonyi)- 1 H- 1,4- benzodiazepin-8-yl] -3-furancarboxamide, dihydrochioride; 7-(3-Chlorophenyl)-2,3 ,4,5-tetrahydro-l1-(1 H-imidazoi-4-ylmethyl)-4-( 1- C) 10 naphthalenylcarbonyl)- 1 H-i ,4-benzodiazepine, di hydrochloride; 2-Methyl-N-[2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-4-( 1 -riaphthalenylcarbonyl)- 1 H-i ,4-benzodiazepin-8-yI]benzamide, dihydrochioride; N-Phenyl-N'-[2,3,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-4-( 1 -naphthalenylcarbonyl)- 1 H-i ,4-benzodiazepin-8-yI]urea, dihydrochioride; 2,3 ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-4-( 1 -naphthalenylcarbonyl)-7-(3- pyridinyl)- 1 H-i ,4-benzodiazepine, trihydrochioride; 2,3 ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-9-methoxy-4-( 1 -naphthalenylcarbonyl)- 1 Hl- 1 ,4-diazepine, di hydrochloride; (R)-2,3,4,5-Tetrahydro- 1 H-imidazoi-4-ylmethyl)-3-[2-(methylthio)ethyl]-4-( 1- naphthalenylcarbonyl)- 1 H-I ,4-benzodiazepine, hydrochloride; 2,3 ,4,5-Tetrahydro- 1-(1 H-imidazol-4-ylmethyl)-4-( 1-naphthalenylcarbonyl)-3 (phenylmethyl)- I H-i ,4-benzodiazepine, hydrochloride; 2,3 ,4,5-Tetrahydro-3-(2-hydroxyethyl)- 1-(1 H-imidazol-4-ylmethyl)-4-( 1- naphthalenylcarbonyi)- I H-i ,4-benzodiazepine, tri fluoroacetate; 2,3 ,4,5-Tetrahydro-4-( 1 H-imidazol-4-ylmethyl)-3-[2-(methylthio)ethyll-4-( 1- naphthalenylcarbonyl)- 1 H-i ,4-benzodiazepine, trifluoroacetate; ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-4-( I -naphthalenylcarbonyl)-3- (phenylmethyl)- 1 H-i ,4-benzodiazepine, trifluoroacetate; 4-Acetyi-7-bromo-2,3 ,4,5-tetrahydro- I H-imidazol-4-ylmethyl)-3 -(phenylmethyl)- I H- 1 ,4-benzodiazepine, hydrochloride; 2,3 ,4,5-Tetrahydro-4-( 1 H-imidazol-4-ylmethyl)- I-naphthalenylcarbonyl)-3 (phenylmethyl)- IH-i ,4-benzodiazepine, 1.5 hydrochloride; 7-Bromo- 1,2,3 ,5-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-3 -(Phenylmethyl)-4H- I,4- benzodiazepine-4-carboxamide, trifluoroacetate; 7-Bromo-2,3 ,4,5-tetrahydro- I H-imidazol-4-ylmethyl)-4-(methylsulfonyl)-3- (phenylmethyl)- I H-I ,4-benzodiazepine, hydrochloride; o 4-Acetyi-2,3 ,4,5-tetrahydro- I H-imidazol-4-ylmethyl)-7-phenyl-3-(phenylmethyl)- I H- 00 1 ,4-benzodiazepine, trifluoroacetate; 4-Acetyl-7-bromo-3-[(4-chlorophenyl)methyl]-2,3 ,4,5-tetrahydro- 1 I H-imidazol-4- ylmethyl)- 1 H-I ,4-benzodiazepine, dihydrochioride; N-Cyclohexyl-N'-[2,3 ,4,5-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-4-( 1- naphthalenylcarbonyl)- 1H-i ,4-benzodiazepin-8-yl] urea, dihydrochioride; 2,2-Dimethyl-N-[2,3,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-4-( 1- naphthalenylcarbonyl)-1I H- 1,4-benzodiazepin-8-yl] propanamide, dihydrochioride; 2,3 ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-4-( 1 -naphthalenylsulfonyl)-7-phenyl- I H- 1 ,4-benzodiazepine, monohydrochioride; 4-Acetyl-7-bromo-2,3 ,4,5-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-3-(2- naphthalenylmethyl)- I H-i ,4-benzodiazepine, dihydrochioride; 4-Acetyl-7-bromo-2,3 ,4,5-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-3 naphthalenylmethyl)- I H-I ,4-benzodiazepine, dihydrochioride; 7-(2-Chlorophenyl)-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-4-( 1- naphthalenylcarbonyl)- I H-I ,4-benzodiazepine, dihydrochioride; 2,3 ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-7-phenyl- 1 H-i ,4-benzodiazepine, monohydrochioride; 1 -Methyl-N-[2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-4-( 1 -naphthalenylcarbonyl)- 1 H-i ,4-benzodiazepin-8-yl]-2-piperidinecarboxamide, trihydrochioride; N-[2,3 ,4,5-tetrahydro- 1 I H-imidazol-4-ylmethyl)-4-( 1 -naphthalenylcarbonyl)- I H- 1,4- benzodiazepin-8-yl]-4-morpholinecarboxamide, di hydrochloride; N-[2,3 ,4,5-Tetrahydro-lI-(I H-imidazol-4-ylmethyl)-4-( 1-naphthalenylcarbonyl)- 1 H- 1,4- benzodiazepin-8-yl] -3 -methylbutanamide, dihydrochioride; 1,2,3 ,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-N,N,7-triphenyl-4H- 1,4-2 benzodiazepine-4-carboxamide, dihydrochioride; 2,3,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-7-phenyl-4-[(4-phenyl- 1 ,2,3-thiadiazol-5- yl)carbonyl] -1H-i ,4-benzodiazepine, tri fluoroacetate; 8- [[(Cyclohexyl am ino)carbonyl] amino] -2,3 ,4,5 -tetrahydro- I H-i m idazolI-4-yl methyl)-3 (phenyimethyl)- 1 H-I ,4-benzodiazepine-4-carboxylic acid, 1, 1 -dimethylethyl ester; 2,3 ,4,5-Tetrahydro- 1 H-imidazoi-4-ylmethyl)-8-[[(4-methylphenyl)sulfonyl]amino]-3- (phenyimethyl)- 1 H-i ,4-benzodiazepine-4-carboxylic acid, 1, 1 -d imethylethyl ester; 7-Bromo- 1,2,3 ,4-tetrahydro- 1 H-imidazol-4-ylmethyi)-3-(phenyimethyi)-5H- 1,4- benzodiazepin-5-one, dihydrochioride; o 2,3,4,5-Tetrahydro- 1 H-imidazoi-4-ylmethyi)-4-[ 1 -oxo-3-( 1 -piperidinyl)propyi]-7- 00 phenyl- 1 H-i ,4-benzodiazepine, trihydrochioride; 2,3 ,4,5-Tetrahydro- 1 H-imidazol-4-yimethyl)-7-phenyl-4-(4-quinoiinyicarbonyl)- I Hl- 1,4- benzodiazepine, tri hydrochioride; 4-[(5-Bromo-3-pyridinyl)carbonyl]-2,3,4,5-tetrahydro-l1-(1 H-imidazol-4-yimethyi)-7- phenyl- I H-I ,4-benzodiazepine, trihydrochioride; IND(S)-4-[2-(Dimethyiamino)-lI-oxo-3-phenyipropyi]-2,3 ,4,5-tetrahydro-l1-(1 H-imidazoi-4- C) 10 yimethyi)-7-phenyi- I H-i ,4-benzodiazepine, trihydrochioride; 2,3 ,4,5-Tetrahydro-4-[4-hydroxy-3-(4-morphoiinyi-methy)benzoy]- 1 H-imidazoi-4- ylmethyl)-7-phenyl- I H-i ,4-benzodiazepine, trihydrochioride; (S)-2,3,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyi)-4-[( 1 -methyl-2-pyrroiidinyi)carbonyl]- 7-phenyl- 1 H-I ,4-benzodiazepine, tri hydrochioride; 2,3 ,4,5-Tetrahydro- 1 H-imidazol-4-yimethyi)-7-phenyl-4-[[2-(propythio)-3- pyridinyl]carbonyl]- 1 H-i ,4-benzodiazepine, trihydrochioride; 4-[(2-Chioro-6-methyi-4-pyridinyl)carbonyl]-2,3 ,4,5-tetrahydro- 1 H-imidazoi-4- ylmethyl)-7-phenyi- I H-i ,4-benzodiazepine, trihydrochioride; 2,3 ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-7-phenyl-4-[[2-(phenylthio)-3- pyridinyi]carbonyl]- 1 H-i ,4-benzodiazepine, trihydrochioride; 2,3,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-4-[[2-(4-methylphenoxy)-3- pyridinyl]carbonyl]-7-phenyl- I H-i ,4-benzodiazepine, trihydrochioride; 2,3 ,4,5-Tetrahydro- 1 H-imidazoi-4-ylmethyl)-4-[(2-methoxy-3-pyridinyl)carbonyl]-7- phenyl- 1 H-i ,4-benzodiazepine, trihydrochioride; 2,3 ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-7-phenyi-4-[(5-pheny-4- oxazolyl)*carbonyl]- 1 H-i ,4-benzodiazepine, dihydrochioride; 4-Acetyi-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-7-phenyl- 1 H-i ,4-benzodiazepine, dihydrochioride; 2,3 ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyi)-7-phenyl-4-[(tetrahydro-3 furanyl)carbonyi]- IH-1 ,4-benzodiazepine, di hydrochioride; 2,3 ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-4-[(2-methoxyethoxy)acety]-7-phenyl- 1 H- I ,4-benzodiazepine, di hydrochloride; 2,3 ,4,5-Tetrahydro- 1 H-imidazol-4-yimethyl)-4-[4-(4-morphoiinylmethyi)benzoyl]-7- phenyl- I H-I ,4-benzodiazepine, tri hydrochloride; 2,3 ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-4-[4-(methylsulfonyl)benzoyl]-7-phenyl- 1 H-i ,4-benzodiazepine, di hydrochloride; o 2,3 ,4,5-Tetrahydro- I H-iniidazol-4-ylmethyl)-4-[ 1 -oxo-3-(phenylsulfonyl)propyl]-7- 00 phenyl- 1 H-I ,4-benzodiazepine, dihydrochioride; 2,3 ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-7-phenyl-4-(3-pyridinylacetyl)- I H- 1,4- benzodiazepine, trihydrochioride; 2,3,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-7-phenyl-4-(2-quinoxalinylcarbonyl)- 1 H- I ,4-benzodiazepine, tetrahydrochioride; IND 2,3 ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-4-(4-isoquinolinylcarbonyl)-7-phenyl-H- C) 10 1 ,4-benzodiazepine, tri hydrochloride; 4-[(2-Chloro-3-pyridinyl)carbonyl]-2,3,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-7- phenyl- I H-i ,4-benzodiazepine, trihydrochioride; 2,3 ,4,5-Tetrahydro- I H-imidazol-4-ylmethyl)-7-phenyl-4-(3 -pyridinylcarbonyl)- 1 H- 1,4- benzodiazepine, trihydrochioride; 4-[(2,6-Dimethoxy-3-pyridinyl)carbonyl]-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-7- phenyl- 1 H-i ,4-benzodiazepine, tri hydrochloride; 2,3 ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-7-phenyl-4-(2-pyrazinylcarbonyl)- 1H- 1,4- benzodiazepine, tetrahydrochioride; 4-(2-Ethoxybenzoyl)-2,3,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-7-phenyl- 1 H- 1,4- benzodiazepine, dihydrochioride; 4-[3-(Dimethylamino)benzoyl]-2,3 ,4,5-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-7-phenyl- 1 H-i ,4-benzodiazepine, tri hydrochloride; 2,3,4,5-Tetrahydro- 1 I H-imidazol-4-ylmethyl)-7-phenyl-4-[( I phenylcyclopropyl)carbonyl]- 1 H-i ,4-benzodiazepine, dihydrochioride; 4-[(Bicyclo[4.2.O]octa- I ,3,5-trien-7-yl)carbonyl]-2,3 ,4,5-tetrahydro- I H-imidazol-4- ylmethyl)-7-phenyl- 1 H-i ,4-benzodiazepine, dihydrochioride; 4-Benzoyl-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-7-phenyl- 1 H- 1,4- benzodiazepine, dihydrochioride; 4-(2-Chlorobenzoyl)-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-7-phenyl- 1 H- 1,4- benzodiazepine, di hydrochloride; 4-(2,3-Dichlorobenzoyl)-2,3 ,4,5-tetrahydro-l1-( IH-imidazol-4-ylmethyl)-7-phenyl- I H- 1,4- benzodiazepine, dihydrochioride; ,4,5-Tetrahydro-lI-( I H-imidazol-4-ylmethyl)-7-phenyl- I H-i ,4-benzodiazepin-4- yl]carbonyl]phenyl]-acetamide, dihydrochioride; 2,3 ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-4-(2-phenoxybenzoyl)-7-phenyl- 1 H- 1,4- benzodiazepine, di hydrochloride; o 2,3 ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-4-(2-methoxybenzoyl)-7-phenyl- 1 H- 1,4- 00 benzodiazepine, d ihydrochloride; 4-(2,3-Dimethoxybenzoyl)-2,3 ,4,5-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-7-phenyl- 1H- I ,4-benzodiazepine, dihydrochioride; 4-(2,4-Dimethoxybenzoyl)-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-7-phenyl- 1 H- 1 ,4-benzodiazepine, dihydrochioride; IND 4-(2,5-Dimethoxybenzoyl)-2,3,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-7-phenyl- I H- 1 ,4-benzodiazepine, dihydrochioride; 4-(2,6-Dimethoxybenzoyl)-2,3 ,4,5-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-7-phenyl- I H- 1 ,4-benzodiazepine, dihydrochioride; 4-(2,3-Dihydroxybenzoyl)-2,3,4,5-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-7-phenyl- 1 H- I ,4-benzodiazepine, dihydrochioride; 1,1 '-Biphenyl]-2-ylcarbonyl)-2,3,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-7-phenyl- 1 H-I ,4-benzodiazepine, dihydrochioride; 2,3 ,4,5-Tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-4-(2-methylbenzoyl)-7-phenyl- I H- 1,4- benzodiazepine, d ihydrochloride; 4-(2,3-Dimethylbenzoyl)-2,3 ,4,5-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-7-phenyl- 1H- 1,4- benzodiazepine, dihydrochioride; 4-(3-Cyanobenzoyl)-2,3 ,4,5-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-7-phenyl- 1H- 1,4- benzodiazepine, dihydrochioride; 4-(3-Chlorobenzoyl)-2,3 ,4,5-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-7-phenyl- 1H- 1,4- benzodiazepine, dihydrochioride; 2,3 ,4,5-Tetrahydro-]1-(1 H-imidazol-4-ylmethyl)-4-(3-phenoxybenzoyl)-7-phenyl- 1 H- 1,4- benzodiazepine, dihydrochioride; 2,3 ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-4-(3-methoxybenzoyl)-7-phenyl- I H- 1,4- benzodiazepine, d ihydrochloride; 4-(3,4-Dimethoxybenzoyl)-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-7-phenyl- 1 H- 1 ,4-benzodiazepine, di hydrochloride; 4-(3 ,5-Dimethoxybenzoyl)-2,3,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-7-phenyl- 1 H- 1 ,4-benzodiazepine, dihydrochioride; 2,3 ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-4-(3-methylbenzoyl)-7-phenyl- I H- 1,4- benzodiazepine, d ihydrochloride; 1,2-Dioxo-2-phenylethyl)-2,3,4,5-tetrahydro- 1 H-imidazol-4-ylmethyi)-7-phenyl- 1 H- 1 ,4-benzodiazepiine, dihydrochioride; o ~4-[(2-Ethoxy-l1-naphthalenyl)carbonyl]-2,3 ,4,5-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-7- 00 phenyl- 1 H-i ,4-benzodiazepine, dihydrochioride; 2,3,4,5-Tetrahydro- 1 H-imidazoi-4-yimethyl)-4-(2-naphthalenylcarbonyl)-7-phenyl- I Hl- 1 ,4-benzodiazepine, dihydrochioride; 4-(Fluorophenylacetyl)-2,3 ,4,5-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-7-phenyl-I1H- 1,4- benzodiazepine, di hydrochloride; ID4-(Diphenylacetyl)-2,3 ,4,5-tetrahydro-l1-(1 H-imidazol-4-yimethyi)-7-phenyl- IH- 1,4- benzodiazepine, dihydrochloride; 2,3,4,5-Tetrahydro-4-(2-hydroxy-l1-oxo-2-phenylpropyl)- 1 H-imidazol-4-ylmethyl)-7- phenyl- 1 H-i ,4-benzodiazepine, dihydrochioride; 2,3,4,5-Tetrahydro-1I H-imidazol-4-ylmethyl)-4-(1 H-indol-2-ylcarbonyl)-7-phenyl-1I H- I ,4-benzodiazepine, dihydrochioride; 2,3 ,4,5-Tetrahydro-l1-(1 H-imidazoi-4-ylmethyl)-4-( I H-indol-3-ylcarbonyl)-7-phenyl- 1 H- I ,4-benzodiazepine, dihydrochioride; 2,3 ,4,5-Tetrahydro- I H-imidazoi-4-ylmethyl)-4-( I H-indol-5-ylcarbonyl)-7-phenyl- 1 H- 1 ,4-benzodiazepine, dihydrochioride; 2,3 ,4,5-Tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-4-[( 1-methyl-i H-indol-2-yl)carbonyl]-7- phenyl- I H-I ,4-benzodiazepine, dihydrochioride; 4-(2-Benzofuranyicarbonyl)-2,3,4,5-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-7-phenyl-1 H- I ,4-benzodiazepine, dihydrochioride; 2,3 ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-7-phenyl-4-(3 -pyridinylcarbonyl)- I H- 1,4- benzodiazepine, N-oxide, dihydrochioride; 2,3 ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-7-phenyl-4-(2-pyridinylcarbonyl)- 1 H-i ,4- benzodiazepine, trihydrochioride; 2,3 ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-7-phenyl-4-(2-quinolinylcarbonyl)- 1 H- 1,4- benzodiazepine, trihydrochioride; 2,3 ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-7-phenyl-4-( I -isoquinolinylcarbonyl)- 1 H- 1 ,4-benzodiazepine, trihydrochioride; 4-(3-Chloro-2-nitrobenzoyi)-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-7-phenyl- 1 H- 1 ,4-benzodiazepine, di hydrochloride; 2,3 ,4,5-Tetrahydro-lI-(1 H-imidazol-4-ylmethyl)-4-(2-nitrobenzoyi)-7-phenyl- 1H- 1,4- benzodiazepine, di hydrochloride; 288 2,3 ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-4-(3-methoxy-2-nitrobenzoyl)-7-phenyl- 1 H-i ,4-benzodiazepine, di hydrochloride; o 2,3 ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-4-( 1 H-indol-4-ylcarbonyl)-7-phenyl- 1 H- 0I 1,4-benzodiazepine, dihydrochioride; 4- [(2,6-Dihydroxy-3 -naphthalenyl)carbonyl]-2,3 ,4,5-tetrahydro-l1-(1 H-imidazol-4- ylmethyl)-7-phenyl- 1 H-I ,4-benzodiazepine, dihydrochioride; 1 H-Benzimidazol-5-ylcarbonyl)-2,3 ,4,5-tetrahydro- I H-imidazol-4-ylmethyl)-7- phenyl- I Hl-i ,4-benzodiazepine, trihydrochioride; IND 4-(1I H-Benzotriazol-5-ylcarbonyl)-2,3,4,5-tetrahydro- I H-imidazol-4-ylmethyl)-7-phenyl- C) 10 1lH- 1,4-benzodiazepine, di hydrochloride; 2,3,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-4-[(4-methoxy-2-quinolinyl)carbonyl]-7- phenyl- 1 H-I ,4-benzodiazepine, trihydrochioride; ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-7-phenyl- I H-i ,4-benzodiazepin-4- yI]carbonyl]phenyl]-acetamide, d ihydrochloride; 2,3 ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-4-(2-methyl- 1 -oxo-2-phenylpropyl)-7- phenyl- 1 H-i ,4-benzodiazepine, di hydrochloride; 4-[2-(Dimethylamino)benzoyl]-2,3,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-7-phenyl- 1 H-I ,4-benzodiazepine, tri hydrochloride; 4-(3-Ethoxybenzoyl)-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-7-phenyl- 1 H- 1,4- benzodiazepine, dihydrochioride; 2,3 ,4,5-Tetrahydro-4-(2-hydroxy[ 1,1 '-biphenyl]-3-ylcarbonyl)- 1-(1 H-imidazol-4- ylmethyl)-7-phenyl- I H-i ,4-benzodiazepine, dihydrochioride; 2,3 ,4,5-Tetrahydro-4-[2-[(2-hydroxyethyl)thio] benzoyl]- 1-(1 H-imidazol-4-ylmethyl)-7- phenyl- 1 H-i ,4-benzodiazepine, dihydrochioride; 2,3 ,4,5-Tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-4-[(2-methoxy-l1-naphthalenyl)carbonyl]-7- phenyl- 1 H-I ,4-benzodiazepine, dihydrochioride; 2,3 ,4,5-Tetrahydro-4-[(2-hydroxy-4-quinolinyl)-carbonyl]- 1 H-imidazol-4-ylmethyl)-7- phenyl- I H-i ,4-benzodiazepine, dihydrochioride; ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-7-phenyl- I H-i ,4-benzodiazepin-4- yl] carbonyl]benzamide, dihydrochioride; 1,1-Dimethylethyl)-2-[[2,3,4,5-tetrahydro- IH-imidazol-4-ylmethyl)-7-phenyl- 1H- I ,4-benzodiazepin-4-yl]carbonyl]benzamide, dihydrochioride; N-(4-Fluorophenyl)-N'-[3-[[2,3 ,4,5-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-7-phenyl-l1H- 1 ,4-berizodiazepin-4-yI] carbonyl] phenyl] urea, dihydrochloride; 2,3 ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-4-[(3-methyl-4-oxo-2-phenyl-4H- benzopyran-8-yl)carbonyl]-7-phenyl- 1H-i ,4-benzodiazepine, dihydrochioride; o 2,3 ,4,5-Tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-7-phenyl-4-[3-(trifluoromethoxy)benzoyl]- 00 1 H-I ,4-benzodiazepine, di hydrochloride; 4-(2-Cyanobenzoyl)-2,3,4,5-tetrahydro- I H-imidazol-4-ylmethyl)-7-phenyl- 1 H- 1,4- benzodiazepine, dihydrochioride; 2,3,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-4-[2-[[(4- methylphenyl)sulfonyl] amino] benzoyl] -7-phenyl- 1 H-i ,4-benzodiazepine, d ihydrochloride; 2,3 ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-7-phenyl-4-(6-quinolinylcarbonyl)- 1 Hl- 1,4- C) 10 benzodiazepine, trihydrochioride; 2,3 ,4,5-Tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-7-phenyl-4-(8-quinolinylcarbonyl)- IH- 1,4- benzodiazepine, tri hydrochloride; 4-(Benzo[b]thiophen-2-ylcarbonyl)-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-7- phenyl-l1H-i ,4-benzodiazepine, dihydrochioride; 4-[[4-(Dimethylamino)- 1 -naphthalenyl~carbonyl]-2,3,4,5-tetrahydro- 1 H-imidazol-4- ylmethyl)-7-phenyl- 1 H-I ,4-benzodiazepine, tri hydrochloride; 2,3 ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-7-phenyl-4-( 1 H-purin-6-ylcarbonyl)- 1 H- 1 ,4-benzodiazepine, trihydrochloride; 2,3 ,4,5-Tetrahydro- 1 I H-imidazol-4-ylmethyl)-4-(methoxyphenylacetyl)-7-phenyl- 1 H- 1,4- benzodiazepine, dihydrochioride; 2,3 ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-4-[(5-methyl- 1 -phenyl- 1 H-pyrazol-4- yl)carbonyl] -7-phenyl- 1 H-i ,4-benzodiazepine, tri hydrochloride; 2,3 ,4,5-Tetrahydro- I H-imidazol-4-ylmethyl)-4-[2-(2-methylphenyl)- 1 -oxopropyl]-7- phenyl- 1 H-i ,4-benzodiazepine, di hydrochloride; 2,3 ,4,5-Tetrahydro- I H-imidazol-4-ylmethyl)-7-phenyl-4-[(tetrahydro-4-phenyl-2H- pyran-4-yI)carbonyl]- 1 H-i ,4-benzodiazepine, dihydrochioride; 2,3,4,5 -Tetrahydro- 1 H-imidazol-4-ylmethyl)-4-[2-(methylphenylamino)benzoyl] -7- phenyl- 1 H-i ,4-benzodiazepine, trihydrochioride; 2,3 ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-7-phenyl-4-(4-quinolinylcarbonyl)- 1 H-I 1,4- benzodiazepine, N-oxide, dihydrochioride; N-Methyl-N-(2-pyridinylmethyl)-2-[[2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-7- phenyl- I H-i ,4-benzodiazepin-4-yl] carbonyl]benzamide, trihydrochioride; 2,3 ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-4-(3-isoquinolinylcarbonyl)-7-phenyl- 1 Hl- 1 ,4-benzodiazepine, tri hydrochloride; 2,3,4,5-Tetrahydro- H-imidazol-4-ylmethyl)-4-[(2-naphthalenylthio)acetyl]- I H- 1,4- benzodiazepine, trifluoroacetate o ~4-L3 ,4-Dimethoxyphenyl)- 1 -oxopropyl]-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)- 00 1 H-i ,4-benzodiazepine, trifluoroacetate 1,1'-Biphenyl]-4-ylacetyl)-2,3,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)- I H- 1,4- benzodiazepine, trifluoroacetate 2,3,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-4-(2-naphthalenylacetyl)- 1 H- 1,4- benzodiazepine, trifluoroacetate IND 1,1 '-Biphenyl]-2-ylcarbonyl)-2,3,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)- I H- 1,4- benzodiazepine, trifluoroacetate 2,3 ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-4-[(2-phenyl4-quinolinyl)carbonyl]- 1 H- 1 ,4-benzodiazepine, trifluoroacetate 2,3,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-4-(3-pyridinylacetyl)- 1 H- 1,4- benzodiazepine, trifluoroacetate 4-(9H-Fiuoren-9-ylacetyl)-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)- I H- 1,4- benzodiazepirie, trifluoroacetate (S)-4-[2-(Dimethylamino)- I -oxo-3-phenylpropyl]-2,3,4,5-tetrahydro- 1 H-imidazol-4- ylmethyl)- 1 H-i ,4-benzodiazepine, trifluoroacetate ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-4-[(2-oxo-4-phenyl-3- oxazolidinyl)acetyl]- 1 H-i ,4-benzodiazepine, trifluoroacetate 4-(9-Acridinylcarbonyl)-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)- 1 H- 1,4- benzodiazepine, trifluoroacetate 2,3 ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-4-(3-phenoxybenzoyl)- I H- 1,4- benzodiazepine, tri fluoroacetate 2,3,4,5-Tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-4-[[4'-(trifluoromethyl)[ 1,1 '-biphenyl]-2- yl]carbonyl]- IH-i ,4-benzodiazepine, trifluoroacetate 2,3 ,4,5-Tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-4-(4-phenoxybenzoyl)- IH- 1,4- benzodiazepine, trifluoroacetate 2,3,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-4-(2-naphthalenylcarbonyl)- 1 H- 1,4- benzodiazepine, trifluoroacetate 2,3 ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-4-( 1 -oxo-4-phenylbutyl)- 1 H- 1,4- benzodiazepine, trifluoroacetate 2,3 ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-4-[(2-phenoxyphenyl)acetyl]- 1 H- 1,4- benzodiazepine, trifluoroacetate 2,3,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-4-[2-[(4-methylphenyl)sulfinyl]benzoyl]- I H-I ,4-benzodiazepine, trifluoroacetate o 2,3 ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-4-[2-[(phenylmethyl)amino]benzoy]- 1 H- 0 1 ,4-benzodiazepine, trifluoroacetate 1,2,3 ,5-Tetrahydro- I H-imidazol-4-yl-methyl)-N,N-diphenyl-4H- 1 ,4-benzodiazepine-4- carboxamide, hydrochloride; 1,2,3 ,5-Tetrahydro- 1 H-imidazol-4-yl-methyl)-a,7-diphenyl-4H- I ,4-benzodiazepine-4- acetic acid, methyl ester, hydrochloride; IND4-Acetyl-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-3-(phenylmethyl)- I H- 1,4- benzodiazepine, hydrochloride; (R)-7-Bromo-2,3 ,4,5-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-4-(methylsulfonyl)-3 (phenylmethyl)- 1 H-i ,4-benzodiazepine, hydrochloride; ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-4-(methylsulfonyl)-3 -(phenylmethyl)- 1 H-I ,4-benzodiazepine-7-carbonitrile, monohydrochloride; (R)-4-Acetyl-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-7-phenyl-3-(phenylmethyl)- 1 H-i ,4-benzodiazepine, monohydrochloride; 7-Bromo-4-[[2-(dimethylamino)ethyl]sulfonyl]-2,3,4,5-tetrahydro- 1 H-imidazol-4- ylmethyl)-3-(phenylmethyl)-4H--1,4-benzodiazepine, trifluoroacetate 2,3 ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-7-phenyl-4-[( 1,2,3 ,4-tetrahydro- I zo quinolinyl)carbonyl]- 1 H-i ,4-benzodiazepine, monohydrochloride; N-Ethyl- 1,2,3 ,5-tetrahydro- I H-imidazol-4-ylmethyl)-N,7-diphenyl-4H- I ,4- benzodiazepine-4-carboxamide, monohydrochloride; 4-[(2,3-Dihydro- 1H-indol-1I-yl)carbonyl]-2,3,4,5-tetrahydro-lI-(I H-imidazol-4-ylmethyl)-7- phenyl- I H-i ,4-benzodiazepine, monohydrochloride; 2,3 ,4,5-Tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-4-(methylsulfonyl)-3 -(phenylmethyl)-7-(4- pyridinyl)- 1 H-i ,4-benzodiazepine, trihydrochioride; (R)-4-[[2-(Dimethylamino)ethyl]sulfonyl]-2,3 ,4,5-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)- 7-phenyl-3-(phenylmethyl)- 1H-I ,4-benzodiazepine, trifluoroacetate [2,3 ,4,5-Tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-4-( 1-naphthalenylcarbonyl)- 1H- 1,4- benzodiazepin-8-yl]carbamic acid, cyclohexyl ester, di hydrochloride; (R)-7-Bromo-2,3,4,5-tetrahydro- 1-(1-methyl-i H-imidazol-5-yl)methyl)-4-(methylsulfonyl)- 3 -(phenylmethyl)- 1 H-i ,4-benzodiazepine, hydrochloride; (R)-7-Cyano-2,3 ,4,5-tetrahydro-l1-[(1-methyl-I H-imidazol-5-yl)metliyl]-4- (methylsulfonyl)-3 -(phenylmethyl)- 1H-i ,4-benzodiazepine, monohydrochioride; 292 4-[2-(4-Chlorophenyl)- 1 ,2-dioxoethyl]-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-7- phenyl- I H-I ,4-benzodiazepine, hydrochloride; o 4-(1I,2-Dioxopropyl)-2,3 ,4,5-tetrahydro- 1 I H-imidazol-4-ylmethyl)-7-phenyl- 1 Hl- 1,4- 00 benzodiazepine, hydrochloride; 2,3 ,4,5-Tetrahydro-l1-(1 H-imidazoL-4-ylmethyl)-4-[2-(4-nitrophenyl)- 1,2-dioxoethyl]-7- phenyl- I H-I ,4-benzodiazepine, hydrochloride; 2,3,4,5-Tetrahydro- 1-(1 H-imidazol-4-ylmethyl)-4-[2-(4-methoxyphenyl)-1I,2-dioxoethyl]-7- phenyl- 1 Hl-i ,4-benzodiazepine, hydrochloride; 2,3 ,4,5-Tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-7-phenyl-4-(3 ,3 ,3-trifluoro- 1,2- C) 10 dioxopropyl)-1IH-1,4-benzodiazepine, trifluoroacetate (R)-7-Bromo-2,3 ,4,5-tetrahydro-l1-(1 IH-imidazol-4-ylcetyl)-4-(methylsulfonyl)-3- (phenylmethyl)- I H-I ,4-benzodiazepine, monohydrochioride; 1 -(R)-7-Bomo-crbnlmn]12,3 ,5-tetrahydro- 1 -2-1H-imidazol-4-yltyl4(methloyl)-3- (phenylmethyl)-1H-1 ,4-benzodiazepine,4croyi acdmonoletedhydrochoride; -[(ylhylrbnlaio-12,3,4,5-tetrahydro- 1 -(1H-imidazol-4-ylmethyl)-43Inptaenlabnl-H14 (peymty)4- 4benzodiazepine-4- pieidn carbox ylc cdmthlese, dihydrochloride; (R)-7-Cyano- 1,2,3 ,5-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-3 -(phenylmethyl)-4H- 1,4- benzodiazepine-4-carboxyl ic acid, ethyl ester, hydrochloride; N-[2,3,4,5-Tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-4-(methylsulfonyl)-3-(phenylmethyl)- 1 H-I ,4-benzodiazepin-8-yl]cyclohexanecarboxamide, dihydrochloride; (R)-7-Cyano-4-[[2-(dimethylamino)ethyl]sulfonyl]-2,3 ,4,5-tetrahydro- 1 H-imidazol-4- ylmethyl)-3-(phenylmethyl)-4H- 1,4-benzodiazepine, dihydrochioride; (R)-7-Cyano-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-4-[[2-(4- morpholinyl)ethyl]sulfonyl]-3-(phenylmethyl)-4H- 1,4-benzodiazepine, dihydrochloride; N-[2,3,4,5-Tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-4-(2-methoxy-3-methylbenzoyl)- 1H- 1 ,4-benzodiazepin-8-yl] cyclohexanecarboxarnide, dihydrochloride, 8-[(Cyclohexylcarbonyl)amino]-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-N-phenyl- 1 H-i ,4-benzodiazepine-4-carboxamide, dihydrochioride; N-[2,3 ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-4-[(2-methylphenyl)sulfonyl]- I H- 1,4- benzodiazepin-8-yl]cyclohexanamide, dihydrochloride; N-[2,3,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-4-[(2-methoxyphenyl)carbonyl]- I H- 1 ,4-benzodiazepin-8-yl]cyclohexanamide, di hydrochloride; (R)-7-Cyano- 1,2,3 ,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-3 -(phenylmethyl)-4H- 1,4- benzodiazepine-4-sulfonic acid, ethyl ester, hydrochloride; o (3R)-7-Bromo- I-[cyano( 1 H-imidazol-4-yl)methyl]-2,3 ,4,5-tetrahydro-4-(methylsulfonyl)-3- 00 (phenylmethyl)- I H-i ,4-benzodiazepine, monohydrochioride; 1-[2-Amino-i H-imidazol-4-yl)ethyl]-2,3 ,4,5-tetrahydro-4-(methylsulfonyl)-3- (phenylmethyl)- 1 H-i ,4-benzodiazepine, dihydrochioride; (3 1 [2-(Dimethyl amino)- I I H-imidazol-4-yl)ethyi]-2,3,4,5-tetrahydro-4- (methylsulfonyl)-3 -(phenylmethyl)- I H-i ,4-benzodiazepine, dihydrochioride; (3 I -[2-Amino- I H-imidazol-4-yl)ethyl]-7-bromo-2,3 ,4,5 -tetrahydro-4- C) 10 (methylsulfonyl)-3 -(phenylmethyl)- 1H-i ,4-benzodiazepine, dihydrochioride; (3 i-[2-(Dimethylamino)- 1-(1 H-imidazol-4-yl)ethyl]-7-bromo-2,3 ,4,5-tetrahydro-4- (methyisulfonyl)-3 -(phenylmethyl)- IH-i ,4-benzodiazepine, dihydrochioride; 7-Cyano-1i,3 ,4,5-tetrahydro-l1-(1-methyl-I H-imidazol-5-ylmethyl)-3-(phenylmethyl)-4- (phenylsul fonyl)-2H-1I,4-benzodiazepin-2-one, monohydrochioride; 7-Cyano- 1,3 ,4,5-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-3-(phenylmethyl)-4- (phenylsulfonyl)-2H-1i,4-benzodiazepin-2-one, monohydrochioride;- 7-Bromo-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-4-(methylsulfonyl)-3-(2- phenylethyl)- 1 H-i ,4-benzodiazepine, dihydrochioride; 7-Bromo-3 -[(3-chlorophenyl)methyl]-2,3,4,5-tetrahydro- I I H-imidazol-4-ylmethyl)-4- !0(methylsuifonyl)-1 H-i ,4-benzodiazepine, dihydrochioride; (R)-7-Bromo-3-(cyclohexylmethyl)-2,3 ,4,5-tetrahydro-l1-( IH-imidazol-4-ylmethyl)-4- (methylsulfonyl)- I H-i ,4-benzodiazepine, dihydrochioride; 7-Bromo-3-[(2-chlorophenyl)methyl]-2,3,4,5-tetrahydro- I I H-imidazol-4-ylmethyl)-4- (methylsulfonyl)- I H-i ,4-benzodiazepine, dihydrochioride; (S)-7-Bromo-3-(cyclohexylmethyl)-2,3 ,4,5-tetrahydro- 1 I H-imidazol-4-yimethyl)-4- (methylsulfonyl)- I H-I1,4-benzodiazepine, dihydrochioride; 7-Bromo-2,3,4,5-tetrahydro- I H-imidazol-4-ylmethyl)-3-[(4-methoxyphenyl)methyl]-4- (methylsulfonyl)- I H-i ,4-benzodiazepine, di hydrochloride; 4 -AcetyI-7-bromo-3-[(2-chlorophenyl)methyl]-2,3,4,5-tetrahydro- I I H-imidazol-4- ylmethyl)- I Hl-1,4-benzodiazepine, dihydrochioride; 4-Acetyi-7-bromo-3-[(3-chlorophenyl)methyl]-2,3 ,4,5-tetrahydro- 1I-(1 H-imidazoi-4- ylmethyl)- 1 H-i ,4-benzodiazepine, dihydrochioride; 7-Bromo-2,3 ,4,5-tetrahydro- I H-imidazol-4-ylmethyl)-3-[(4-hydroxyphenyl)methyl]-4- (methylsulfonyl)- I H-I ,4-benzodiazepine, dihydrochioride; ,4,5-Tetrahydro- I H-imidazol-4-ylmethyl)-4-(methylsulfonyl)-7-phenyl-3-(3- pyridinylmethyl)- 1 H-i ,4-benzodiazepine, dihydrochioride; o 2,3,4,5-Tetrahydro-8-(hydroxymethyl)- 1 H-imidazol-4-ylmethyl)-4-( 1- 00 naphthaienylcarbonyl)- I H-I ,4-benzodiazepine, di hydrochloride; 2,3,4,5-Tetrahydro- 1 H-imidazol-4-yimethyl)-4-( 1 -naphthalenylcarbonyl)-8- (phenoxymethyl)- 1 H-i ,4-benzodiazepine, di hydrochloride; N-Cyclohexyl-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-4-( 1 -naphthalenylcarbonyl)- 1 H-i ,4-benzodiazepine-8-carboxamide, dihydrochioride; N-(Cyclohexylmethyl)-2,3,4,5-tetrahydro- I H-imidazol-4-ylmethyl)-4-( I C) 10 naphthalenylcarbonyl)- 1 H-I ,4-benzodiazepine-8-carboxamide, dihydrochioride; 2,3 ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-4-( 1 -naphthalenylcarbonyl)-N- (phenylmethyl)- 1 H-I ,4-benzodiazepine-8-carboxamide, dihydrochioride; (R)-4-Acetyi-7-[2-[(dimethylamino)methyi]phenyl]-2,3 ,4,5-tetrahydro- 1 H-imidazol-4- ylmethyl)-3-(phenylmethyl)- 1 H-i ,4-benzodiazepine, dihydrochioride; (R)-4-Acetyl-7-cyano-2,3,4,5-tetrahydro- I H-imidazol-4-ylmethyl)-3 -(phenylmethyl)- 1 H-i ,4-benzodiazepine, monohydrochioride; (R)-7-Cyano-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-4-( I -oxobutyl)-3- (phenylmethyl 1 H-i ,4-benzodiazepine, monohydrochioride; (R)-7-Cyano-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-yimethyl)-4-(2-methyl- 1 -oxopropyl)-3- (phenylmethyl)- 1 H-I ,4-benzodiazepine, monohydrochioride; (R)-7-Cyano-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyi)-3-(phenylmethyl)-4-(2- pyridinylacetyl)- 1 H-I ,4-benzodiazepine, dihydrochioride; (R)-7-Cyano-2,3,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-3 -(phenylmethyl)-4-(2- thienyisulfonyl)- I H-I ,4-benzodiazepine, monohydrochioride; (R)-7-Cyano-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-4-[( 1 -methylethyl)sulfonyl]-3- (phenylmethyl)- 1 H-i ,4-benzodiazepine, monohydrochioride; (R)-7-Cyano-2,3 ,4,5-tetrahydro- I H-imidazol-4-ylmethyl)-3 -(phenylmethyl)-4- [(trifluoromethyl)sulfonyl]- 1H-I ,4-benzodiazepine, monohydrochioride; (R)-7-Bromo-2,3 ,4,5-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-3 -(phenylrnethyl)-4- (propylsulfonyl)- 1 H-i ,4-benzodiazepine, monohydrochioride; (R)-7-Bromo-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-3-(phenylmethyl)-4- (phenylsulfonyl)- 1H-I ,4-benzodiazepine, monohydrochioride; ,4,5-Tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-7-phenyl-3-(phenylmethyl)-4- (phenylsulfonyl)-1 H-i ,4-benzodiazepine, monohydrochioride; ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-7-phenyl-3-(phenylmethyl)-4- (propylsulfonyl)- 1 H-I ,4-benzodiazepine, monohydrochioride; o (R)-7-Cyano-4-[(4-fluorophenyl)sulfonyl]-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)- 00 3 -(phenylmethyi)- 1 H-i ,4-benzodiazepine, monohydrochioride; (R)-7-Cyano-4-[(3-cyanophenyl)sulfonyi]-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)- 3-(phenylmethyl)- I H-i ,4-benzodiazepine, monohydrochioride; (R)-7-Cyano-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-4[( 1-methyl- I H-imidazoi-2- yl)sulfonyl]-3-(phenylmethyl)-IH-1 ,4-benzodiazepine, dihydrochioride; (R)-4-[(3-Bromophenyl)sulfonyi]-7-cyano-2,3 ,4,5-tetrahydro-l1-(1 H-imidazol-4-yimethyl)- 3-(phenylmethyl)- I H-i ,4-benzodiazepine, monohydrochioride; (R)-N-[5-[[7-cyano-2,3 ,4,5-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-3 -(phenylmethyl)- IH- I ,4-benzodiazepin-4-yl] suifonyl] -4-methyl-2-thiazolyl] acetamide, dihydrochioride; 4-Acetyl-2,3 ,4,5-tetrahydro-l1-(1 H-imidazol-4-ylmethyi)-3-(phenylmethyl)-7-(4-pyridinyl)- I H-i ,4-benzodiazepine, trihydrochioride; 2,3 ,4,5-Tetrahydro-lI-(1 H-imidazol-4-ylmethyl)-4-(2-phenyl- 1,2-dioxoethyl)-7-(4- pyridinyl)- I H-i ,4-benzodiazepine, tri hydrochloride; 2,3,4,5-Tetrahydro- I H-imidazoi-4-ylmethyl)-7-(4-pyridinyl)-4-[2- (trifluoromethoxy)benzolyl]-1 H-I ,4-benzodiazepine, trihydrochioride; ,4,5-Tetrahydro-l1-[(i-methyl-i H-imidazol-5-yl)methyl]-4-(methylsulfonyl)-7- phenyi-3 -(phenylmethyl)- 1H-i ,4-benzodiazepine; (R)-7-Cyano-2,3 ,4,5-tetrahydro-l1-(1 H-imidazoi-4-yimethyl)-4-(phenylacetyl)-3 (phenylmethyl)- 1 H-i ,4-benzodiazepine, monohydrochioride; 4-(2-Benzothiazolyl)-2,3 ,4,5-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-7-phenyl- 1H- 1,4- benzazepine, trihydrochioride; 2,3 ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-3-(phenylmethyl)-7-(3-pyridinyl)-4- (trifluoroacetyl)- I H-I ,4-benzodiazepine, trihydrochioride; 2,3,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyi)-4-(methylsulfonyl)-3-(phenylmethyl)-7-(3- pyridinyl)- 1 H-i ,4-benzodiazepine, tri hydrochloride; 7-Bromo-3 -dimethylethoxy)methyl]- 1,2,3 ,4-tetrahydro- I H-imidazol-4-ylmethyl)- 5H- 1,4-benzodiazepin-5 -one; 7-Bromo-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-yimethyl)-4-(methylsulfonyl)-3 (phenoxymethyl)- 1 H-I ,4-benzodiazepine, di hydrochloride; 7-Bromo-2,3 ,4,5-tetrahydro-3-(hydroxymethyl)- I H-imidazol-4-ylmethyl)-4- (methylsulfonyl)- I H-i ,4-benzodiazepine, monohydrochioride; 7-Bromo-3-[(1,1I -dimethylethoxy)methyl]-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)- 4-(methylsulfonyl)- I H-i ,4-benzodiazepine; o [7-Bromo-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-yimethyl)-3 -(phenylmethyl)- I H- 1,4- 00 benzodiazepin-8-yl]carbamic acid, 2-methyipropyl ester, trihydrochioride; [4-Acetyl-7-bromo-2,3 ,4,5-tetrahydro- I H-imidazol-4-yimethyl)-3-(phenylmethyl)- 1 H- I ,4-benzodiazepin-8-yI]carbamic acid, 2-methyipropyl ester; N-[4-Acetyl-2,3,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-3-(phenylmethyl)- I H- 1,4- benzodiazepin-8-yI]cyclohexanecarboxamide, dihydrochioride; IND[7-Bromo-2,3 ,4,5-tetrahydro-l1-( I H-imidazol-4-ylmethyl)-4-(methylsulfonyl)-3 (phenylmethyl)-1IH-1,4-benzodiazepin-8-yl]carbamic acid, 2-methyipropyl ester; ,4,5-Tetrahydro- I H-imidazol-4-ylmethyl)-4-(phenylsulfonyl)-3-(phenylmethyl)- 1 H-i ,4-benzodiazepine-7-carbonitrile, monohydrochioride; 7-Bromo- 1 ,2,3,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-3-(phenylmethyl)-4H- 1,4- benzodiazepine-4-acetamide; 7-Bromo-4-[(dimethylamino)acetyl]-2,3,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-3- (phenylmethyl)- 1 H-I ,4-benzodiazepine; (R)-7-Bromo-4-( 1,2-dioxopropyl)-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-3- (phenylmethyl)- 1 H-i ,4-benzodiazepine, trifluoroacetate; (R)-7-Bromo-4-(cyclopropylcarboonyl)-2,3 ,4,5-tetrahydro- I H-imidazol-4-ylmethyl)-3- zo (phenylmethyl)- 1 H-i ,4-benzodiazepine, trifluoroacetate; (R)-7-Cyano-2,3,4,5-tetrahydro-1I -(I1H-imidazol-4-ylmethyl)-3 -(phenylmethyl)-4- (propylsulfonyl)- I H-i ,4-benzodiazepine, monohydrochioride; 7-Bromo-2,3,4,5-tetrahydro- I ,4-bis(1 H-imidazol-4-ylmethyl)-3 -(phenylmethyl)- 1 H- 1,4- benzodiazepine, dihydrochioride; 7-Bromo-1I,2,3 ,5-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-N,N-dimethyl-3-(phenylmethyl)- 4H-1I,4-benzodiazepine-4-sul fonamide, monohydrochioride; 2,3 ,4,5-Tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-4-(methylsulfonyl)-3-(phenylmethyl)- 1H- 1 ,4-benzodiazepine-7-carbonitrile, monohydrochioride; (R)-7-Cyano- 1,2,3 ,5-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-N,N-dimethyl-3 (phenylmethyl)-4H- 1,4-benzodiazepine-4-carboxamide, monohydrochioride; N,N-Diethyl-2,3 ,4,5-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-4-(methylsulfonyl)-3 (phenylmethyl)- 1 H-i ,4-benzodiazepine-7-carboxamide, monohydrochioride; 2,3 ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-7-phenyl-4-( 1 -phenyl- I 1 H-I ,4-benzodiazepine, monohydrochloride; 297 (R)-7-Cyano-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-3 -(phenylmethyl)-4-(2- pyrazinylcarbonyl)-4H- 1,4-benzodiazepine, monohydrochioride; o (R)-4-[7-Bromo-2,3 ,4,5-tetrahydro- I H-imidazol-4-ylmethyl)-3-(phenylmethyl)-4H- 1,4- 00 benzodiazepin-4-yl] -4-oxobutanoic acid, methyl ester, monohydrochioride; (R)-7-Cyano-2,3,4,5-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-4-(4-morpholinylcarbonyl)-3 (phenylmethyl)- 1 H-I ,4-benzodiazepine, monohydrochioride; (R)-7-Cyano-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-3 -(phenylmethyl)-4-[[2-( 1- pyrrolidinyl)ethyl]sulfonyl]- 1H-I ,4-benzodiazepine, dihydrochioride; ,4,5-Tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-4-(methylsulfonyl)-7-phenyl-3 pyridinylmethyl)- I H-I ,4-benzodiazepine, dihydrochioride; (R)-2,3,4,5-Tetrahydro-l1-( IH-imidazol-4-ylmethyl)-7-phenyl-3-(3-pyridinylmethyl)-4-(2- thienylsulfonyl)- I H-I ,4-benzodiazepine, dihydrochioride; (R)-2,3,4,5-Tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-7-phenyl-4-(propylsulfonyl)-3-(3- pyridinylmethyl)- 1 H-i ,4-benzodiazepine, monohydrochioride; (R)-7-Bromo-2,3,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-4-(methylsulfonyl)-3-(2- pyridinylmethyl)- 1 H-I ,4-benzodiazepine, monohydrochioride; 2,3 ,4,5-Tetrahydro- 1 H-imidazol-4-yimethyl)-4-(methyisulfonyl)-3-(phenylmethyl)-7-(2- pyrimidinyl)- 1 H-i ,4-benzodiazepine, dihydrochioride; (R)-7-Bromo-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-3 -(phenylmethyl)-4- [(trifluoromethyl)sulfonyl]- IH-i ,4-benzodiazepine, monohydrochloride; ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-7-phenyl-3-(phenylmethyl)-4- (trifluoroacetyl)- 1 H-I ,4-benzodiazepine, monohydrochioride; ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-4-(methylsulfonyl)-3-(phenylmethyl)- 7-(4-pyridinyl)- I H-i ,4-benzodiazepine, dihydrochioride; (R)-2,3,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-3-(phenylmethyl)-7-(4-pyridinyl)-4-(2- thienylsulfonyl)- 1 H-i ,4-benzodiazepine, dihydrochioride; ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-3 -(phenylmethyl)-4-(phenylsul fonyl)- 7-(4-pyridinyl)- 1 H-i ,4-benzodiazepine, dihydrochioride; (R)-2,3,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-3-(phenylmethyl)-4-(propylsulfonyl)-7- (4-pyridinyl)- 1 H-i ,4-benzodiazepine, dihydrochioride; (R)-7-Cyano-2,3 ,4,5-tetrahydro- I H-imidazol-4-ylmethyl)-3-(phenylmethyl)-4-[(3 dimethyl-isoxazol-4-yl)sulfonyl]- 1H-i ,4-benzodiazepine, dihydrochioride; (R)-7-Cyano-4- [(4-cyanophenyl)sulfonyl] -2,3 ,4,5-tetrahydro-l1-( IH-imidazol-4-ylrnethyl)- 3 -(phenylmethyl)- 1 H-i ,4-benzodiazepine, dihydrochioride; 298 (R)-7-Cyano-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-3-(phenylmethyl)-4-[(2,2,2- trifluoroethyl)sulfonyl]- 1 H-i ,4-benzodiazepine, dihydrochioride; C.) 00 3-(phenylmethyl)- IH-I ,4-benzodiazepine, d ihydrochloride; (R)-7-Cyano-2,3 ,4,5-tetrahydro-l1-(1 H-imidazoi-4-ylmethyl)-4-[(4- methoxyphenyl)sulfonyl] -3-(phenylmethyl)- 1H-i ,4-benzodiazepine, di hydrochloride; N-[[7-Bromo-2,3,4,5-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-4-(methylsulfonyl)-lIH- 1,4- benzodiazepin-3 -yI] methyl] benzamide, dihydrochioride; (R)-7-Cyano- 1 ,2,3,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-N,N-dimethyl-3- (phenylmethyl)-4H-1I,4-benzodiazepine-4-sulfonamide, hydrochloride; (R)-7-Cyano- 1,2,3 ,5-tetrahydro-N,N-dimethyl-l1-[(1-methyl-i H-imidazol-5-yl)methyl]-3- (phenyimethyl)-4H- 1,4-benzodiazepine-4-sulfonamide, hydrochloride; (R)-7-Chloro-2,3 ,4,5-tetrahydro-l1-[(1-methyl-I H-imidazol-5-yI)methyl]-4- (methylsulfonyl)-3-(phenylmethyl)- IH-i ,4-benzodiazepine, monohydrochioride; (R)-7-Chloro-2,3 ,4,5-tetrahydro-l1-(1 H-imidazoi-4-ylmethyl)-4-(methylsulfonyl)-3 (phenylmethyl)- I H-i ,4-benzodiazepine, monohydrochloride; (R)-7-Chloro-2,3 ,4,5-tetrahydro-l1-[(1-methyl-i H-imidazol-5-yl)methyl]-4- (phenyisulfonyl)-3 -(phenylmethyl)- 1H-i ,4-benzodiazepine, monohydrochioride; (R)-7-Cyano-2,3,4,5-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-3 -(pyridin-3-ylmethyl)-4- (methylsulfonyl)- I H-i ,4-benzodiazepine, tetrahydrochloride; (R)-7-Bromo-2,3 ,4,5-tetrahydro-l1-(1 H-imidazoi-2-ylmethyi)-4-(methylsulfonyl)-3 (phenylmethyl)- 1 H-I ,4-benzodiazepine, dihydrochloride; (R)-7-Bromo-2,3 ,4,5-tetrahydro-l1-(1 H-imidazol-4-yimethyl)-4-[( 1-methyl-i H-imidazol-4- yl)sulfonyl]-3 -(phenylmethyl)- 1 H-i ,4-benzodiazepine, tri hydrochloride; (R)-7-Chloro-2,3 ,4,5-tetrahydro-l1-(1 -methyl-imidazol-5-ylmethyl)-4-[(2-morpholin-4-yl- ethyl)sulfonyl]-3-(phenylmethyl)- 1H-i ,4-benzodiazepine, dihydrochioride; (R)-7-Chloro-2,3 ,4,5-tetrahydro-l1-(1 H-imidazol-4-yimethyl)-4-[(2-morpholin-4-yl- ethyl)sulfonyl]-3-(phenylmethyl)- I H-I ,4-benzodiazepine, dihydrochioride; (R)-7-Chloro-4-[(dimethylamino)sulfonyl]- I-[(1-methyl-i H-imidazol-5-yl)methyi]-3- (phenylmethyl)- I H-i ,4-benzodiazepine, monohydrochloride; (R)-7-Chloro-2,3 ,4,5-tetrahydro-l1-(1 -methyl-imidazol-5-ylmethyl)-4-[(4-methyl-piperidin- 4-yI-ethyl)sulfonyl]-3-(phenylmethyl)- 1H-I ,4-benzodiazepine, dihydrochioride; (R)-7-Bromo-2,3 ,4,5-tetrahydro-l1-(1 -methyl-imidazoi-5-ylmethyl)-4-[(4-methyl-piperidin- 4-yl-ethyl)suifonyl]-3-(phenylmethyl)- I H-I ,4-benzodiazepine, dihydrochloride; (R)-7-Cyano- 1,2,3 ,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-3-(phenylmethyl)-4H- 1,4- benzodiazepine-4-carboxylic acid, isopropyl ester, hydrochloride; o(R)-7-Bromo-2,3,4,5-tetrahydro-4-[[2-( I H-imidazol-1I-yl)ethyl]sulfonyl]- 1 -mdzl4 00 ylmethyl)-3 -(phenylmethyl)- 1 H-I ,4-benzodiazepine, dihydrochioride; (R)-7-Cyano-2,3 ,4,5-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-4-(propylsulfonyl)-3-(3- pyridinylmethyl)-l1H-i ,4-benzodiazepine, hydrochloride; 7-Bromo-2,3,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-3-(phenylmethyl)- 1 H- 1,4- hydrochloride; (R)-7-Bromo-2,3 ,4,5-tetrahydro-l1-(1 H-imidazol-1I-ylacetyl)-4-(methylsulfonyl)-3 C) 10 (phenylmethyl)- IH-I ,4-benzodiazepine, trifluoroacetate; I 1,2,4,5-Tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-2-(2-phenylethyl)-3 H-I ,4-benzodiazepin-3- one; 2,3,4,5-Tetrahydro- I H-imidazol-4-ylmethyl)-4-(methylsulfonyl)-2-(2-phenylethyl)- 1 H- I ,4-benzodiazepine, monohydrochioride; 1 5 ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-4-(methylsulfonyl)-7-phenyl-3-(4- pyridinylmethyl)- 1 H-I ,4-benzodiazepine, dihydrochioride; ,4,5-Tetrahydro- 1 H-imidazol-2-ylmethyl)-4-(phenylsulfonyl)-3 -(phenylmethyl)- 1 H-I ,4-benzodiazepine-7-carbonitri le, hydrochloride; (R)-7-Cyano- 1,2,3,5 -tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-N,N-dimethyl-3 pyridinylmethyl)-4H-1I,4-benzodiazepine-4-carboxamide, dihydrochioride; (R)-7-Cyano- 1,2,3 ,5-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-N,N-dimethyl-3 pyridinylmethyl)-4H- 1,4-benzodiazepine-4-sul fonamide, dihydrochioride; ,4,5-Tetrahydro- 1 -(4-cyanophenylmethyl)-imidazol-5-ylmethyl)-4- (methylsulfonyl)-3-(phenylmethyl)-1H-1 ,4-benzodiazepine-7-carbonitrile, hydrochloride; ,4,5-Tetrahydro- 1 -(4-cyanophenylmethyl)-imidazol-4-ylmethyl)-4- (methylsulfonyl)-3 -(phenylmethyl)- 1H-I ,4-benzodiazepine-7-carbonitri le, hydrochloride; (R)-4-Benzoyl-7-cyano-2,3 ,4,5-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-3 -(phenylmethyl)- 1 Hl-I ,4-benzodiazepine, monohydrochioride; (R)-7-Cyano-2,3 ,4,5 -tetrahydro-l1-[(1-methyl-i H-imidazol-5-yl)methyl]-3-(pyridin-3- ylmethyl)-4-(methylsulfonyl)- 1 Hl-i ,4-benzodiazepine, d ihydrochloride; (R)-7-Cyano-2,3 ,4,5-tetrahydro-l1-[(1-methyl-i H-imidazol-5-yI)methyl]-3-(pyridin-3- ylmethyl)-4-(propylsulfonyl)- 1 H-i ,4-benzodiazepine, trihydrochloride; (R)-7-Cyano-2,3,4,5-tetrahydro- H-imidazol-4-yl)methyl]-3-(pyridin-3 -ylmethyl)-4- (phenylsulfonyl)- 1 H-i ,4-benzodiazepine, dihydrochloride; 2,3,4,5-Tetrahydro- I H-imidazol-4-yimethyl)-4-(methylsulfonyi)-7-phenyl-3- (phenyimethyl)- I H-i ,4-benzodiazepine; o 1,2,3 ,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-N-( I -naphthalenyl)-7-phenyl-4H- 1,4- 00 benzodiazepine-4-carboxamide, monohydrochioride; (S)-7-Bromo-2,3 ,4,5-tetrahydro-lI-(I H-imidazol-4-ylmethyl)-4-(methylsulfonyl)-3 (phenylmethyl)- 1 H-i ,4-benzodiazepine, hydrochloride; N-[2,3 ,4,5-Tetrahydro-l1-(1 H-imidazol-4-ylmethyi)-4-(2,3-dimethylbenzoyl)- 1 H- 1,4- benzodiazepin-8-yl]cyclohexanecarboxamide, dihydrochioride; IND(R)-7-Cyano-N-[2-(dimethyiamino)ethyl]-2,3 ,4,5-tetrahydro-l1-(1 H-imidazo1-4-yimethyl)- N-methyl-3-(phenylmethyl)- 1 H-i ,4-benzodiazepine-4-carboxamide, trifluoroacetate 7-Bromo-2,3 ,4,5-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-4-(methylsulfonyl)-2-oxo-3- (phenylmethyl)- 1 H-i ,4-benzodiazepine, trifluoroacetate; (R)-7-Cyano-4-(2-furanylcarbonyl)-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-3- (phenylmethyl)- 1 H-i ,4-benzodiazepine, trifluoroacetate 1); (R)-7-Cyano-2,3,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-4-[(4-nitrophenyl)sulfonyl]-3- (phenyimethyl)- 1 H-I ,4-benzodiazepine, trifluroracetate; (R)-7-Cyano-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-4-[[4-(4-methyi- I1- piperazinyl)phenyl] sulfonyl]-3-(phenylmethyl)- IH-i ,4-benzodiazepine, trifluoroacetate; (R)-7-Cyano-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-4-[[(4- dimethylamino)phenyl]sulfonyi]-3-(phenylmethyl)- 1H-i ,4-benzodiazepine, trifluoroacetate; (R)-7-Bromo-4-[[2-(dimethylamino)ethyl]sulfonyl]-2,3 ,4,5-tetrahydro- 1 H-imidazol-4- ylmethyi)-3-(phenylmethyl)-4H- 1,4-benzodiazepine, dihydrochioride; (R)-7-Cyano-2,3 ,4,5-tetrahydro- 1 H-imidazoi-4-ylmethyl)-3-(phenylmethyl)-4-(3- pyridinylsulfonyl)- 1 H-I ,4-benzodiazepine, tri hydrochloride; 2,3 ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-4-(methylsulfonyl)-3-(phenylmethyl)- 1 H- 1 ,4-benzo-diazepine, d ihydrochloride; (R)-7-Bromo-2,3 ,4,5-tetrahydro-lI-[(1-methyl-I H-imidazoi-4-yI)methyl]-4- (methylsulfonyi)-3 -(phenylmethyl)- I H-i ,4-benzodiazepine, dihydrochioride; [3 -(Dimethylamino)propyl] sulfonyl] -2,3,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)- 7-phenyl-3-(phenylmethyl)- 1 H-i ,4-benzodiazepine, dihydrochioride; (R)-7-Cyano-2,3 ,4,5 -tetrahydro- 1 H-imidazol-4-ylmethyl)-3 -(phenylmethyl)- 1 H- 1,4- benzodiazepine, trihydrochioride; 4-Butyl-2,3 ,4,5-tetrahydro-lI-(1 H-imidazol-4-ylmethyl)-3-(phenylmethyl)- 1 H- 1,4- benzodiazepine, trihydrochioride; 301 (R)-7-Bromo-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-4-[[2-(4- morpholi'nyl)ethyl]sulfonyl]-3 -(phenylmethyl)- IH-i ,4-benzodiazepine, d ihydrochloride; o (R)-7-Bromo-2,3 ,4,5-tetrahydro-l1-[(1-methyl-i H-imidazol-5-yl)methyl]-4-[[2-(4- 00 morpholinyl)ethyl] sulfonyl]-3 -(phenylmethyl)- IH-I ,4-benzodiazepine, dihydrochioride; (R)-7-Cyano- 1 I H-imidazol-4-ylmethyl)-4-(4-morpholinylsulfonyl)-3-(phenylmethyl)- I H- 1 ,4-benzodiazepine, monohydrochioride;. (R)-7-Cyano- 1 -+(1-methyl- I H-imidazol-5-yl)methyl]-4-[(4-morpholinyl)sulfonyl]-3- (phenylmethyl)- I H-i ,4-benzodiazepine, monohydrochioride; (R)-7-Cyano-2,3 ,4,5-tetrahydro- I H-imidazol-4-ylmethyi)-4-[(4-aminophenyl)sulfonyl]- C) 10 3-(phenylmethyl)- 1 H-i ,4-benzodiazepine, hydrochloride; 2,3 ,4,5-Tetrahydro- I H-imidazol-4-ylmethyl)-4-[(4-pyridylthio)acetyl]-7-phenyl- 1 H- 1,4- benzodiazepine, di hydrochioride; N-(4-Chlorophenyl)-N'-cyano- 1 ,2,3,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-7-phenyl-4H- 1 ,4-benzodiazepine-4-imidamide, monohydrochioride; 4-Acetyl-7-bromo- 1,2,4,5, I '-hexahydro-l1-(1 H-imidazol-4-ylmethyl)spiro[3 H- 1,4- benzodiazepine-3,2'-[2H]indene], dihydrochioride; 7-Bromo-4-[3-(dimethylamino)-lI-oxopropyl]-2,3 ,4,5-tetrahydro-l1-(1 H-imidazol-4- ylmethyl)-3-(phenylmethyl)- 1H-i ,4-benzodiazepine, trifluoroacetate ,4,5-Tetrahydro-l1-(1-methyl- 1H-imidazol-5-ylmethyl)-4-(phenylsul fonyl)-3- (phenylmethyl)- I H-i ,4-benzodiazepine-7-carbonitrile, monohydrochioride; 2,3 ,4,5-Tetrahydro-lI-[(i-methyl- 1H-imidazol-5-yl)-methyl]-4-(methyl-sulfonyl)-7-phenyl- 3-(pyridin-3-yI-methyl)- 1H-i ,4-benzodiazepine, hydrochloride (1:1 trifluoroacetate (1:0.75) salt; 4-[4-(Fluorophenyl)sulfonyl]-2,3 ,4,5-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-2-(2- phenylethyl)- 1 H-i ,4-benzodiazepine, monohydrochloride; 7-Bromo-2,3,4,5-tetrahydro- 1 H-imidazol-4-yI-methyl)-4-(methyl-sulfonyl)-2-(2- phenylethyl)- 1 H-i ,4-benzodiazepine, monohydrochloride; (R)-7-Cyano-2,3 ,4,5-tetrahydro- I -methyl- I H-imidazol-5-ylmethyl)-4-[[2-( I morpholinyl)ethyl]sulfonyl]-3-(phenylmethyl)- 1 H-I ,4-benzodiazepine, dihydrochioride; (R)-7-Bromo-2,3 ,4,5-tetrahydro- I H-imidazol-4-ylmethyl)-4-(methyl-sulfonyl)-3-(4- bromophenylmethyl)- I H-i ,4-benzodiazepine, hydrochloride; (R)-7-Bromo-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-4-(methyl-sulfonyl)-3- (thiazol-4-ylmethyl)- 1 Hl-I ,4-benzodiazepine, hydrochloride; (R)-7-Bromo-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-4-(propyl-sulfonyl)-3-(thiazol- 4-ylmethyl)-l1H-i ,4-benzodiazepine, hydrochloride; C) 00 bromophenylmethyl)- I H-I ,4-benzodiazepine, hydrochloride; (R)-7-Bromo-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-3-(pyridin-3 -ylmethyl)-4- (methylsulfonyl)- I H-i ,4-benzodiazepine, trihydrochioride; (R)-7-Bromo-2,3 ,4,5-tetrahydro- 1 H- I -methyl-imidazol-5-ylmethyl)-3-(pyridin-3 yimethyl)-4-(methylsulfonyl)- I H-i ,4-benzodiazepine, dihydrochioride; IND (R)-7-Cyano-2,3 ,4,5-tetrahydro- 1 H-imidazoi-4-ylmethyl)-4-(phenyi-sulfonyl)-3-(4- C) 10 cyanophenylmethyl)- 1 H-i ,4-benzodiazepine, hydrochloride; (R)-7-Cyano-4-[(N-methyl-N-phenylmethyl)aminosulfonyl]- I H-imidazol-4-yl)methyl]- 3 -(phenylmethyl)- I H-i ,4-benzodiazepine, monohydrochioride; (R)-7-Cyano-4-[N-(tetrahydroisoquinolinyi)sulfonyl]- I H-imidazol-4-yl)methyl]-3- (phenylmethyl)- I H-I ,4-benzodiazepine, monohydrochloride; (R)-7-Cyano-2,3 ,4,5-tetrahydro- I H-imidazol-4-ylmethyl)-4-(phenylsufonyl)-3 thienylmethyl)- I H-i ,4-benzodiazepine, hydrochloride; cis-2,3 ,4,5-Tetrahydro-1I,5-bis( 1 H-imidazoi-4-ylmethyl)-3-(phenylmethyl)- 1 H- benzodiazepine-2-carboxylic acid ethyl ester, trifluoroacetate (R)-7-Cyano-4-[(N-piperidinyl)sulfonyi]- 1I H-imidazol-4-yl)methyl]-3-(phenylmethyl)- 1 Hl-i ,4-benzodiazepine, monohydrochloride; (R)-7-Cyano-2,3 ,4,5-tetrahydro- 1 H- I -methyl-imidazol-5-ylmethyl)-3-(phenylmethyl)-4- (2-thienylsulfonyl)- 1 H-i ,4-benzodiazepine, hydrochloride; (R)-7-Cyano-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-yimethyl)-3-(pyridin-3 -ylmethyl)-4-[[2- (dimethylamino)ethyl] sulfonyl] I H-i ,4-benzodiazepine, trihydrochloride; (R)-7-Cyano-2,3 ,4,5-tetrahydro- 1 H- I -methyl-imidazol-5-ylmethyl)-3-(phenylmethyl)-4- (propylsulfonyl)- I H-I ,4-benzodiazepine, hydrochloride; N-(Cyano)-N'-methyl- 1,2,3 ,5-tetrahydro- 1 H-imidazoi-4-ylmethyi)-7-phenyl-4H- 1,4- benzodiazepine-4-imidamide, hydrochloride; (R)-7-Cyano-4-[(2-nitrophenyl)-sulfonyl]-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-3- (phenyl-methyl)-l1H-i ,4-benzodiazepine, hydrochloride; R)-7-Cyano-4-[(4-methyl-phenyi)sulfonyl]-2,3,4,5-tetrahydro- I H-imidazol-4-ylmethyl)- 3-(phenylmethyl)- 1 H-I ,4-benzodiazepine, hydrochloride; (R)-7-Cyano-4-(butylsulfonyl)-2,3,4,5-tetrahydro- 1 H-imidazoi-4-ylmethyl)-3- (phenylmethyl)- 1 H-i ,4-benzodiazepine, hydrochloride; 303 (R)-7-Cyano-4-[(2-trifluoro-methylphenyl)sulfonyl]-2,3,4,5-tetrahydro- 1 H-imidazol-4- ylmethyl)-3-(phenylmethyl)- I H-i ,4-benzodiazepine, hydrochloride; o(R)-7-Cyano-4-[(2-trifluoromethoxyphenyl)sulfonyl]-2,3,4,5-tetrahydro- 1 -mdzl4 00 ylmethyl)-3 -(phenylmethyl)- IH-I ,4-benzodiazepine, hydrochloride; (R)-7-Cyano-4-[(2-methoxy-carbonylphenyl)sulfonyl]-2,3 ,4,5-tetrahydro- 1 H-imidazol-4- ylmethyl)-3-(phenylmethyl)- 1 H-i ,4-benzodiazepine, hydrochloride; (R)-7-Cyano-4-[(2-methyl-sulfonylphenyl)sulfonyl]-2,3 ,4,5-tetrahydro- 1 H-imidazol-4- ylmethyl)-3-(phenylmethyl)- 1 H-I ,4-benzodiazepine, hydrochloride; (R)-7-Cyano-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-3-(phenylmethyl)-4-(((4- C) 10 methylsulfonyl)-phenyl)-sulfonyl)- 1 H-I ,4-benzodiazepine; (N (R)-7-Cyano-2,3,4,5-tetrahydro- I H-imidazol-4-ylmethyl)-3 -(phenylmethyl)-4-(((4- trifluoromethyl)-phenyl)-sulfonyl)- I H-i ,4-benzodiazepine; (R)-7-Cyano-2,3 ,4,5 -tetrahydro- 1 I H-imidazol-4-ylmethyl)-3-(phenylmethyl)-4-((3 methoxypropyl)-sulfonyl)- I H-i ,4-benzodiazepine; (R)-7-Cyano-2,3 ,4,5-tetrahydro- 1 I H-imidazol-4-ylmethyl)-3 -(phenylmethyl)-4-((3 ,4- dimethoxyphenyl)-sulfonyl)- I H-i ,4-benzodiazepine; (R)-7-Cyano-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-3-((4-fluorophenyl)methyl)-4- (phenylsulfonyl)-1 HF-i ,4-benzodiazepine; (R)-7-Cyano-4-[(N-cyclopropylmethyl-N-propyl)-aminosulfonyl]- 1 H-imidazol-4- yl)methyl] -3-(phenylmethyl)- 1 Hl-i ,4-benzodiazepine; (R)-7-Cyano-4-[(N,N-(dibutylamino))-sulfonyl]- I H-imidazol-4-yl)methyl]-3- (phenylmethyl)- I H-i ,4-benzodiazepine; 1 ,2,3,4-Tetrahydro-7-bromo-4-[(1 H-imidazol-4-yl)methyl]-2-phenylmethyl- I (methylsulfonyl)quinoxaline; (R)-7-Cyano-2,3 ,4,5-tetrahydro- I H-imidazol-4-ylmethyl)-3-(phenylmethyl)-4- ((imidazol-4-yl)methylsulfonyl)- I Hl-I ,4-benzodiazepine; (R)-7-Cyano-2,3,4,5-tetrahydro- 1 I H-imidazol-4-ylmethyl)-3 -((2-thienyl)methyl)-4- (propylsulfonyl)- I Hl-I ,4-benzodiazepine; (R)-7-Cyano-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyi)-3-((2-thienyl)methyl)-4-((2- thienyl)-sulfonyl)- I H-i ,4-benzodiazepine; (R)-7-Cyano-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-3-(phenylmethyl)-4-((3 methylthiopropyl)-sulfonyl)- I H-i ,4-benzodiazepine; (R)-7-Cyano-2,3 ,4,5-tetrahydro- 1 H-imidazoi-4-ylmethyl)-3 -(phenylmethyl)-4-(((3- methylthioxo)-propyl)-sulfonyl)- I Hl-I ,4-benzodiazepine; (R)-7-Cyano-2,3,4,5-tetrahydro- I H-imidazol-4-ylmethyl)-3-(phenylmethyl)-4-(((3- methylsulfonyl)-propyl)-sulfonyl)-lI H-i ,4-benzodiazepine; o (R)-7-Cyano-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-3 -(phenylmethyl)-4-((2- 00 methylpropyl)-sulfonyl)- I H-i ,4-benzodiazepine; (R)-7-Cyano-2,3,4,5-tetrahydro- I H-imidazol-4-ylmethyl)-3 -(phenylmethyl)-4-30 (cyclopentylsulfonyl)- 1 H-I ,4-benzodiazepine; (R)-7-Cyano-2,3 ,4,5-tetrahydro- I H-imidazol-4-ylmethyl)-3 -(phenylmethyl)-4-((4,4,4- trifluorobutyl)-sulfonyl)- 1 H-I ,4-benzodiazepine; (R)-7-Cyano-2,3 ,4,5-tetrahydro- I H-imidazol-4-ylmethyl)-3 -(phenylmethyl)-4- C) 10 ((phenylmethyl)-sulfonyl)- I H-i ,4-benzodiazepine; (R)-7-Cyano-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-3-(phenylmethyl)-4-[[2-(5-(N- benzoyl)-aminomethyl)-thienyl]-sulfonyl]- 1 H-i ,4-benzodiazepine (R)-7-Cyano-2,3 ,4,5-tetrahydro- I H-imidazol-4-ylmethyl)-3-(phenylmethyl)-4-[[2-( 1-(3- chloro-5-methyi-pyridin-2-yl))-pyrrolyl]-suifonyl]- 1 H-i ,4-benzodiazepine; (R)-7-Cyano-2,3 ,4,5-tetrahydro- 1 H-imidazoi-4-ylmethyl)-3-(phenylmethyl)-4-((4- carboxyphenyl)-sulfonyl)- I H-I ,4-benzodiazepine; (R)-7-Cyano-2,3 ,4,5 -tetrahydro- I H-imidazol-4-ylmethyl)-3 -(phenylmethyl)-4- methyl-I ,2,4-oxadiazol-5-yl)-phenyl)-sulfonyl]- 1 H-I ,4-benzodiazepine; (R)-7-Cyano-2,3 ,4,5 -tetrahydro- 1 H-imidazol-4-ylmethyl)-3 -(phenylmethyl)-4-((2,5 dimethoxyphenyl)-sul fonyl)-1I H-i ,4-benzodiazepine; (R)-7-Cyano-4-[(N-tetrahydroquinolinyl)sulfonyi]- 1 H-imidazol-4-yl)methyl]-3- (phenylmethyl)- 1 H-i ,4-benzodiazepine; (R)-7-Cyano-4-[(N,N-bis-[l -(2-methylpropyl)amino]-sulfonyl]- 1 H-imidazol-4- yI)methyl]-3-(phenylmethyl)-1I H-i ,4-benzodiazepine; (R)-7-Cyano-4-[(N-methyl-N-phenyl)aminosulfonyl]- 1 H-imidazol-4-yl)methyl]-3- (phenylmethyl)- I H-i ,4-benzodiazepine; (R)-7-Cyano-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyi)-3 -(2-(2,6-dimethylphenyl)- ethyl)-4-(methylsulfonyl)- 1 H-i ,4-benzodiazepine; (R)-7-Cyano-2,3 ,4,5-tetrahydro- 1 I -(N-phthalimidoethyl)-imidazol-5-ylmethyl)-3- (phenylmethyl)-4-(methylsulfonyl)- 1 H-I ,4-benzodiazepine; (R)-7-Cyano-2,3 ,4,5-tetrahydro-lI-j[(2-(N ,N-dimethylamino)-ethyl)-imidazol-5-ylmethyl]-3- (phenylmethyl)-4-(methylsulfonyl)- 1 H-i ,4-benzodiazepine; (R)-7-Cyano-2,3 ,4,5-tetrahydro- 1 -[(2-aminoethyl)-imidazol-5-ylmethyl]-3-(phenylmethyl)- 4-(methylsulfonyl)- 1 H-i ,4-benzodiazepine; (R)-4-(methanesulfonyl)-2,3,4,5-tetrahydro- I H-imidazol-4-ylmethyl)-3-(phenylmethyl)- 1 H-8-oxo-pyrimidino[4,5-e]- 1 ,4-diazepine; o (R)-7-Cyano-2,3 ,4,5 -tetrahydro- 1 H-imidazol-4-ylmethyl)-3 -((4-(2-methoxyethoxy)- 00 phenyl)methyl)-4-(phenylsulfonyl)- 1 H-i ,4-benzodiazepine; (R)-7-Cyano-2,3,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-3 -((4-(2-(dimethylamino)- ethoxy)-phenyl)methyl)-4-(phenylsulfonyl)- IH- 1,4-benzodiazepine; (R)-7-Cyano-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylsulfonyl)-3-(phenylmethyl)-4- (methylsulfonyl)- 1 H-i ,4-benzodiazepine; (R)-7-Cyano-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylsulfonyl)-3 -(phenylmethyl)-4- (propylsulfonyl)- 1 H-i ,4-benzodiazepine; (R)-7-Cyano-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylsulfonyl)-3-(phenylmethyl)-4- (phenylsulfonyl)- 1 H-I ,4-benzodiazepine; (R)-7-Cyano-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylsulfonyl)-3-(phenylmethyl)-4-(2- thienylsulfonyl)- 1 H-i ,4-benzodiazepine; 7-Cyano-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-3-(R)-[(R)- I -phenyl -ethyl]-4- (methylsul fonyl)- 1 H-i ,4-benzodiazepine; 7-Cyano-2,3,4,5-tetrahydro- I H-imidazol-4-ylmethyl)-3-(R)-[(R)- 1 -phenyl -ethyl] -4- (propylsulfonyl)- I H-i ,4-benzodiazepine; 7-Cyano-2,3,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-3-(R)-[(R)- 1 -phenyl -ethyl]-4- (phenylsulfonyl)-1I H-I ,4-benzodiazepine; 7-Cyano-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-3-(R)-[(R)- I -phenyl -ethyl] thienyl)-suifonyl)- 1 H-i ,4-benzodiazepine; 7-Cyano-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-3 1 -phenyl -ethyl] -4- (methylsulfonyl)- 1 H-I ,4-benzodiazepine; 7-Cyano-2,3 ,4,5-tetrahydro- I H-imidazol-4-ylmethyl)-3-(S)-[(R)- 1 -phenyl -ethyl]-4- (propylsulfonyl)- 1 H-i ,4-benzodiazepine; 7-Cyano-2,3,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-3-(S)-[(R)- I -phenyl -ethyl]-4- (phenylsulfonyl)- 1 H-I ,4-benzodiazepine; 7-Cyano-2,3 ,4,5-tetrahydro- I H-imidazol-4-ylmethyl)-3-(S)-[(R)- 1 -phenyl -ethyl] thienyl)-sulfonyl)- 1 H-i ,4-benzodiazepine; 7-Cyano-2,3 ,4,5-tetrahydro- I H-imidazol-4-ylmethyl)-3-(R)-[(S)- 1 -phenyl -ethyl] -4- (methylsulfonyl)- I H-i ,4-benzodiazepine; 7-Cyano-2,3,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-3-(R)-[(S)- 1 -phenylI-ethyl] -4- (propylsulfonyl)-1I H-I ,4-benzodiazepine; 7-Cyano-2,3 ,4,5-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-3-(R)-[(S)- i -phenyl -ethyl]-4- (phenylsulfonyl)- I H-i ,4-benzodiazepine; o 7-Cyano-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-3-(R)-[(S)- I -pheny I-ethyl] 00 thienyl)-sulfonyl)- 1 H-I ,4-benzodiazepine; 7-Cyano-2,3 ,4,5-tetrahydro- I H-imidazol-4-ylmethyl)-3-(S)-[(S)- I -phenyl -ethyl]-4- (methylsulfonyl)- I H-i ,4-benzodiazepine; 7-Cyano-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-3-(S)-[(S)- I -phenyl-ethyl]-4- (propylsulfonyl)- 1 H-I ,4-benzodiazepine; 7-Cyano-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-3-(S)-[(S)- 1 -phenyl -ethyl] 4- 810((phenysulfonyl)- I H-i ,4-benzodiazepine; 7-Cyano-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-3-(S)-[(S)- I -phenylI-ethyl] thienyl)-sulfonyl)- I H-i ,4-benzodiazepine; 7-Cyano-2,3,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-3-(R)-[(R)-phenylcyclopropyl)-4- (methylsulfonyl)- 1 H-i ,4-benzodiazepine; 7-Cyano-2,3 ,4,5-tetrahydro- I H-imidazol-4-ylmethyl)-3-(R)-[(R)-phenylcyclopropyl)-4- (propylsulfonyl)- 1 H-i ,4-benzodiazepine; 7-Cyano-2,3 ,4,5-tetrahydro- I H-imidazol-4-ylmethyl)-3-(R)-[(R)-phenylcyclopropyl)-4- (phenylsulfonyl)- 1 H-i ,4-benzodiazepine; 7-Cyano-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-3-(R)-[(R)-phenylcyclopropyl)-4- zo ((2-thienyl)-sulfonyl)- 1 H-i ,4-benzodiazepine; 7-Cyano-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-3-(R)-[(S)-phenylcyclopropyl)-4- (methylsulfonyl)- I H-i ,4-benzodiazepine; 7-Cyano-2,3 ,4,5-tetrahydro- I H-imidazol-4-ylmethyl)-3-(R)-[(S)-phenylcyclopropyl)-4- (propylsulfonyl)- 1 H-i ,4-benzodiazepine; 7-Cyano-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-3-(R)-[(S)-phenylcyclopropyl)-4- (phenylsulfonyl)- 1 H-i ,4-benzodiazepine; 7-Cyano-2,3,4,5-tettahydro- I H-imidazol-4-ylmethyl)-3-(R)-[(S)-phenylcyclopropyl)-4- ((2-thienyl)-sulfonyl)- I H-i ,4-benzodiazepine; 7-Cyano-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-3-(S)-[(R)-phenylcyclopropyl)-4 (methylsulfonyl)- I H-i ,4-benzodiazepine; 7-Cyano-2,3,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-3-(S)-[(R)-phenylcyclopropyl)-4- (propylsulfonyl)- 1 H-i ,4-benzodiazepine; 7-Cyano-2,3,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-3-(S)-[(R)-phenylcyclopropyl)-4- (phenylsulfonyl)-1I H-I ,4-benzodiazepine; 7-Cyano-2,3 ,4,5-tetrahydro-1 H-imidazol-4-ylmethyi)-3-(S)-[(R)-phenylcyclopropyi)-4- ((2-thienyl)-sulfonyl)- 1 H-i ,4-benzodiazepine; o 7-Cyano-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-3-(S)-[(S)-phenylcyclopropyl)-4- 00 (methylsulfonyl)- 1 H-i ,4-benzodiazepine; 7-Cyano-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-3-(S)-[(S)-phenylcyclopropyl)-4- (propylsulfonyl)- 1 H-i ,4-benzodiazepine; 7-Cyano-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-3-(S)-[(S)-phenylcyclopropyl)-4- (phenylsulfonyl)- 1 H-i ,4-benzodiazepine; 7-Cyano-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-3-(S)-[(S)-phenylcyclopropyl)-4- C) 10 ((2-thienyl)-suifonyi)- 1 H-I ,4-benzodiazepine; (R)-7-Cyano-2,3,4,5-tetrahydro- 1 H-imidazol-4-yimethyl)-3 -(phenylmethyl)-4-[(2-(5- (pyridin-2-yl))-thienyl)-sulfonyi])- I H-i ,4-benzodiazepine; (R)-7-Cyano-2,3,4,5-tetrahydro- 1 I H-imidazol-4-ylmethyl)-3-(phenylmethyl)-4-[(2-(5- (1 ,2-isoxazol-3-yl))-thienyl)-sulfonyl])- 1 H-I ,4-benzodiazepine; (R)-7-Cyano-2,3 ,4,5-tetrahydro- 1 1 H-imidazol-2-yl)-propyl)-3 -(phenylmethyl)-4- (phenylsulfonyl)- 1 H-I ,4-benzodiazepine; (R)-7-Cyano-2,3 ,4,5-tetrahydro- 1 H-imidazoi-2-yI)-propyl)-3-(phenylmethyl)-4- (methylsulfonyl)- I H-i ,4-benzodiazepine; (R)-7-Cyano-2,3 ,4,5 -tetrahydro- I H-imidazol-2-yI)-propyl)-3-(phenylmethyl)-4- (propylsuifonyl)- 1 H-i ,4-benzodiazepine; (R)-7-Cyano-2,3 ,4,5-tetrahydro- 1 1 H-imidazol-2-yl)-propyl)-3-(phenylmethyl)-4-((2- thienyl)-sulfonyl)-1I H-i ,4-benzodiazepine; (R)-7-Cyano-2,3 ,4,5-tetrahydro- 1 H-imidazoi-2-yI)-ethyisulfonyl)-3-(phenylmethyl)- 4-(phenylsulfonyl)- 1 H-I ,4-benzodiazepine; (R)-7-Cyano-2,3 ,4,5-tetrahydro- I H-imidazoi-2-yl)-ethylsulfonyi)-3 -(phenyimethyl)- 4-(methylsulfonyl)- I H-I ,4-benzodiazepine; (R)-7-Cyano-2,3 ,4,5-tetrahydro- I H-imidazol-2-yI)-ethylsulfonyl)-3-(phenylmethyl)- 4-(propylsulfonyl)- 1 H-i ,4-benzodiazepine; (R)-7-Cyano-2,3 ,4,5 -tetrahydro- 1 H-imidazoi-2-yl)-ethylsulfonyl)-3-(phenyimethyl)- 4-((2-thienyl)-suifonyl)- 1 H-i ,4-benzodiazepine; (R)-7-Cyano-2,3 ,4,5-tetrahydro- I H-imidazoi-4-yimethyl)-3 -(phenylmethyl)-4-(( 1- oxoethyl)-amino)- I H-i ,4-benzodiazepine; (R)-7-Cyano-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-3-(phenylmethyl)-4- (methanesulfonylamino)- 1 H-I ,4-benzodiazepine; O (R)-7-Cyano-2,3,4,5-tetrahydro-l-(1 H-imidazol-4-ylmethyl)-3-(phenylmethyl)-4- (phenylsulfonylamino)-1 H-1,4-benzodiazepine. C.) O oO 133. The method claim 130, wherein the compound has the formula 0 NH ,R 2 N H wherein RI is selected from Cl, Br, phenyl, pyridyl or cyano and R 2 is selected from substituted aralkyl or substituted heterocycloalkyl.
102. 134. The method claim 130, wherein the compound has the formula R 1 NH H wherein R, is selected from Cl, Br, phenyl, pyridyl or cyano and R 2 is selected from substituted aralkyl or substituted heterocycloalkyl.
103. 135. The method claim 130, wherein the compound has the formula ID 0 R 3 R0 C" R 1 Z N 00R2 N H O c wherein O RI is selected from Cl, Br, phenyl, pyridyl or cyano; 0 5 R 2 is selected from substituted aralkyl or substituted heterocycloalkyl; R 3 is selected from substituted alkyl, substituted aryl or substituted heterocyclo; ZI is selected from CO, SO 2 CO 2 CONHRs, SO3, SO 2 NRs, or C(NCN)NR 5 R 5 is selected from hydrogen, lower alkyl, substituted alkyl, aryl or substituted aryl.
104. 136. The method of claim 130, wherein the compound has the formula Z R 3 N R2 N <(CH2)n+l N I Prot wherein Ri is selected from Cl, Br, phenyl, pyridyl or cyano; R 2 is selected from substituted aralkyl or substituted heterocycloalkyl; R 3 is selected from substituted alkyl, substituted aryl or substituted heterocyclo; ZI is selected from CO, SO 2 CO 2 CONHR 5 SO 3 SO 2 NR 5 or C(NCN)NR 5 Prot is triphenylmethyl or Boc; and Rs is selected from hydrogen, lower alkyl, substituted alkyl, aryl or substituted aryl. 310 IO
105. 137. A method of treating a synucleinopathic subject, the method comprising, O administering to a synucleinopathic subject a farnesyl transferase inhibitor compound of the 00 formula: C R 4 R IND SN-Z--R 8 N C, N R/ Ss-Ttm v V R, R 2 R3 N R 6 R 7 or a stereoisomeric form, or a pharmaceutically acceptable acid or base addition salt form thereof, in a therapeutically effective amount, wherein nis 1; r, s and t are 0 or 1; pis 0, 1 or 2; V, W and X are selected from the group consisting of oxygen, hydrogen, R 2 and R /CN N 0 CN N C- N-C--N -N-SO 2 C- R 13 R14 0 -0 2 S-N-N- 0 NR 20 R 21 N NR 22 RFi R 17 R R 19 Z and Y are selected from the group consisting of CHR 9 SO 2 SO 3 CO, C0 2 O, NR'O, SO 2 NR", CONR 2 IO Sor Z may be absent; C R 6 R 7 R 9 R, R R 1 R 1 R 15 R 1 6 R 1 7 R 1 9 R 20 R 2 1 R 22 R 24 R 25 R 26 R 28 SR 29 R 3 R 31 R 32 ,R R 3 4, R 3 R 35 and R 38 are selected from the group consisting of 00 hydrogen, lower alkyl, substituted alkyl, aryl and substituted aryl; R 4 and R 5 are selected from the group consisting of hydrogen, halo, nitro, cyano and U--R 23 \O U is selected from the group consisting of sulfur, oxygen, NR 24 CO, SO, SO2, CO 2 ,NR 2 CO2, NR 26 CONR 27 NR 2 8 2 NR 29 S NR0 S2 NR, NR 32 CO, CONR 3 3 P0 2 R 34 IN and P0 3 R or U is absent; 0 10 R 2 and R are selected from the group consisting of hydrogen, alkyl, alkoxycarbonyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, aralkyl, cycloalkyl, aryl, substituted aryl, heterocyclo, substituted heterocyclo, cyano, carboxy, carbamyl and substituted carbamyl; R 8 and R 23 are selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, aralkyl, cycloalkyl, aryl, substituted aryl, heterocyclo and substituted heterocyclo; any two of R 2 and R 3 may be joined to form a cycloalkyl group; R, S and T are selected from the group consisting of CH 2 CO and CH(CH 2 )pQ wherein Q is NR 36 R 37 OR 38 or CN; and A, B, C and D are carbon; with the provisos that V and W are not both oxygen; W and X together may be oxygen only ifZ is either absent, O, NR'O, CHR 9 N(R 4 N(R 5 )--SO2 R 23 may be hydrogen except when U is SO, SO2, NR 25 CO 2 or NR 28 S02 and R 8 may be hydrogen except when Z is SO2, C0 2 N(RiS)--SO 2 0 NR 20 R 21 N NR 22 or S--
106. 138. The method according to claim 137, wherein the pharmaceutically acceptable salt is mesylate.
107. 139. The method according to claim 138, wherein the compound is (R)-7-cyano- 2,3 ,4,5-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-3-(phenylmethyl)-4-(2-thienylsulfonyl)- 1 H- 1,4- o benzodiazepine, mesylate salt. 00
108. 140. The method according toclaim 137, wherein the compound is selected from the group consisting of: 2,3 ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-4-( 1 -naphthalenylcarbonyl)- I H- 1,4- benzodiazepine, hydrochloride; 8-Chloro-2,3 ,4,5-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-4-( 1-naphthalenylcarbonyl)- 1 H- 1,4- benzodiazepine, hydrochloride; 2,3 ,4,5-Tetrahydro-l1-(1 H-imidazol-4-yl-methyl)-2-methyl-4-( 1-naphthalenylcarbonyl)- 1 H- 1,4- benzodiazepine, hydrochloride; 2,3 ,4,5-Tetrahydro-4-( 1-naphthalenylcarbonyl)- -(phenylmethyl)- 1 yl]methyl]- 1 H-i ,4-benzodiazepine, hydrochloride; 1 5 2,3 ,4,5-Tetrahydro-( 1 H-imidazol-4-yl-methyl)-4-( 1 -naphthalenylsulfonyl)- 1 H- 1,4- benzodiazepine, hydrochloride; ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-3-[2-(methylthio)ethyl]-4-( 1- naphthalenylcarbonyl)- 1 H-i ,4-benzodiazepine, hydrochloride; 2,3 ,4,5-Tetrahydro- 1 H-imidazol-4-yl-methyl)-N-methyl-N-phenyl-4H- 1 ,4-benzodiazepine- 4-carboxamide, hydrochloride; 2-[2,3 ,4,5-Tetrahydro- 1 H-imidazol-4-yl-methyl)- 1 H-I ,4-benzodiazepin-4- yl]sulfonyljbenzoic acid, methyl ester, hydrochloride; 7-Bromo-2,3,4,5-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-4-( 1-naphthalenylcarbonyl)- I H- 1,4- benzodiazepine, hydrochloride; 2,3 ,4,5-Tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-4-( 1-naphthalenenylcarbonyl)-7-phenyl- I H- 1 ,4-benzodiazepine, hydrochloride; 2,3 ,4,5-Tetrahydro- 1 H-imidazol-2-ylmethyl)-4-( 1 -naphthalenylcarbonyl)- 1 H- 1,4- benzodiazepine, dihydrochioride; 2,3 ,4,5-Tetrahydro- 1 H-imidazol-2-yl)propyl]-4-( 1-naphthalenylcarbonyl)- 1 H- 1,4- benzodiazepine, dihydrochloride; 1 -[3-Amino-3-( I H-imidazol-2-yl)propyl]-2,3 ,4,5-tetrahydro-4-( 1 -naphthalenylcarbonyl)- I H- 1 ,4-benzodiazepine, trihydrochloride; 2,3 ,4,5-Tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-3-methyl-4-( I-napthalenylcarbonyl)- I H- 1,4- benzodiazepine, hydrochloride; ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-3-[2-(methylthio)ethyl]-4-( 1- __naphthalenylmethyl)- 1 H-i ,4-benzodiazepine, hydrochloride; o 2,3 ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-9-methyl-4-( 1 -naphthalenylcarbonyl)- 1 H- 1,4- 00 benzodiazepine, dihydrochioride; 1 -[[2-(2-Aminoethyl)- 1 H-imidazol-4-ylmethyl-2,3,4,5-tetrahydro-4-( 1-naphthalenylcarbonyl)- 1 H-I ,4-benzodiazepine, trihydrochioride; I -[[2-Aminomethyl)- 1 H-imidazol-4-yl]methyl]-2,3 ,4,5-tetrahydro-4-( 1 -naphthalenylcarbonyl)- I H-I ,4-benzodiazepine, tri hydrochloride; IDN-[2,3 ,4,5-Tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-4-( 1 -naphthalenylcarbonyl)- 1 H- 1,4- C) 10 benzodiazepin-8-yl]acetamide, dihydrochioride; 2,3 ,4,5-Tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-4-( 1-naphthalenylcarbonyl)- I H-naphtho[2,3- 1,4-diazepine, dihydrochioride; 2,3 ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-4-( 1 -naphthal enyl carbonyl)- 8-nitro- 1 H- 1,4- benzodiazepine, dihydrochioride; 2,3 ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-4-( 1 -naphthalenylcarbonyl)-8 -amino- I H- 1,4- benzodiazepine, di hydrochloride; N-[2,3,4,5Tetrahydro- 1 H-imidazol-4-ylmethyl)-4-( 1-naphthalenylcarbonyl)- 1 H- 1,4- benzodiazepin-8-yl] benzamide, dihydrochioride; N-[2,3,4,5-Tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-4-( I-naphthalenylcarbonyl)-l1H- 1,4- !O benzodiazepin-8-yI]cyclohexanamide, dihydrochioride; 2,3 ,4,5-Tetrahydro-lI-[2-( 1H-imidazol-4-yl)ethyl]-4-( 1-riaphthalenylcarbonyl)- 1 H- 1,4- benzodiazepine, d ihydrochloride; 2,3 ,4,5-Tetrahydro-lI-[2-( 1 H-imidazol-4-yl)ethyl]-4-( 1-naphthalenylcarbonyl)-7-phenyl- I H- 1 ,4-benzodiazepine, d ihydrochloride; 7-Bromo-2,3 ,4,5-tetrahydro-l1-[2-( 1H-imidazol-4-yl)ethyl]-4-(l1-naphthalenylcarbonyl)- 1H- 1,4- benzodiazepine, dihydrochioride; 1 -(2-Aminoethyl)- 1 H-imidazol-5-yl]methyl]-2,3 ,4,5-tetrahydro-4-naphthalenylcarbonyl)-7- phenyl- I H-i ,4-benzodiazepine, trihydrochioride; 2,3 ,4,5Tetrahydro- 1 H-imidazol-4-ylmethyl)-7-phenyl- I H-i ,4-benzodiazepine-4-carboxylic acid, phenylmethyl ester; 2,3 ,4,5-Tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-7-phenyl-4-[2-(trifluoromethoxy)benzoyl]- I H- 1 ,4-benzodiazepine; 1 ,2,3,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-N-methyl-N,7-diphenyl-4H- 1,4- benzodiazepine-4-carboxamide, dihydrochioride; 2,3,4,5 ,-Tetrahydro- I H-imidazol-4-yimethyl)-4-( I -naphthaleneylcarbonyl)-7-( I piperidinylsulfonyl)- I H-i ,4-benzodiazepine, monohydrochioride; o 2,3 ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-4-( 1 -naphthalenylcarbonyl)-7-pyridin-2-yl- 1 H- 00 1 ,4-benzodiazepine, tri hydrochloride; 7-(2-Furanyl)-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-4-( 1 -naphthalenylcabonyl)- 1 H- 1 ,4-benzodiazepine, di hydrochioride; 2,3 ,4,5-Tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-4-( 1-naphthalenylcarbonyl)-7-(2-thienyi)- IH- 1 ,4-benzodiazepine, dihydrochioride; IND2,3 ,4,5-Tetrahydro- I H-imidazol-4-ylmethyl)-4-( I -naphthalenylcarbonyl)-7-(4-pyridinyl)- 1 H-I ,4-benzodiazepine, tri hydrochloride; 2,3 ,4,5-Tetrahydro- 1 H-imidazol-2-yl)propyfl-4-( I -naphthalenytcarbonyl)-7-phenyl- I H- 1 ,4-benzodiazepine, dihydrochioride; 2,3 ,4,5-Tetrahydro-1I,4-bis( I H-imidazol-4-ylmethyl)-7-phenyl- I H-I ,4-benzodiazepine, dihydrochioride; 2,3 ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-4-( 1 -naphthalenylmethyl)-7-phenyl- 1 H- 1,4- benzodiazepi ne, trifluoroacetate; 2,3 ,4,5-Tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-7-methoxy-4-( 1-naphthalenylcarbonyl)- IH- 1 ,4-benzodiazepine, d ihydrochloride; 2,3 ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-4-(l1-naphthalenylcarbonyl)- 1 H- 1,4- benzodiazepine-7-carboxylic acid, dihydrochioride; 2,3 ,4,5-Tetrahydro- 1 H-imidazol-5-ylmethyl)-4-( 1-naphthalenylcarbonyl)-7-cyclohexyl- I H- I ,4-benzodiazepine, 2,5 hydrochloride; 7-Butyl-2,3,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-4-( 1 -naphthalenylcarbonyl)- I H- 1,4- benzodiazepine, dihydrochioride; 1 -[[2-(2-Aminoethyl)- 1 H-imidazol-4-yl]methyl]-2,3 ,4,5-tetrahydro-4-( 1- naphthalenylcarbonyl)-7-phenyl- 1 H-i ,4-benzodiazepine, trihydrochioride; I -[[2-(Aminomethyl)- I H-imidazol-4-y!]methyl]-2,3 ,4,5-tetrahydro-4-( 1 -naphthalenylcarbonyl)- 7-phenyl-]IH-i ,4-benzodiazepine, trihydrochioride; 2,3 ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-4-( I -naphthalenylcarbonyl)-8-[N,N- bis(phenyl-methyl)amino] -1 H-i ,4-benzodiazepine, trihydrochioride; N-[2,3 ,4,5-Tetrahydro- 1 H-imidazol-4-yl-methyl)-4-( 1 -naphthalenylcarbonyl)- 1 H- 1,4- benzodiazepin-8yl]phenylsulfonamide, dihydrochioride; N-Phenyl-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-yl-methyl)-4-( 1 -naphthalenylcarbonyl)- 1 H- 1,4- benzo-diazepine-7carboxamide, dihydrochloride; N-[2,3 ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-4-( I -naphthalenylcarbonyl)- I H- 1,4- benzodiazepin-8-y1]-3-methylbenzamide, dihydrochioride; o N-[2,3 ,4,5-Tetrahydro-l1-(1 H-imidazol-4-ylmethyi)-4-( I-naphthalenylcarbonyl)- 1 H- 1,4- 00 benzodiazepin-8-yl]-4-methylbenzamide, dihydrochioride; 3 -Chloro-N- [2,3 ,4,5 -tetrahydro- 1 H -im idazol1-4-yl -methyl)-4-( 1 -naphtha]lenyl carbonyl)- I H- 1 ,4-benzo-diazepin-8-yl]benzamide, dihydrochioride; 7-Bromo-2,3,4,5,-tetrahydro- 1 -[[2-[(dimethylamino)-methyl]- 1H-imidazol-4-yl]methyl]-4-( I- naphthalenylcarbonyl)- 1 H-i ,4-benzodiazepine, dihydrochioride; 7-(4-Chlorophenyl)-2,3,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-4-( 1- naphthalenylcarbonyl)- 1 H-i ,4-benzodiazepine, dihydrochioride; 7-(3-Aminophenyl)-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-4-( 1- naphthalenylcarbonyl)- I H-I ,4-benzodiazepine, trihydroehioride; I -Methyl-N-[2,3,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-4-( 1 -naphthalenylcarbonyl)- 1 H- I ,4-benzodiazepin-8-yl]- 1 H-pyrrole-2-carboxamide, trihydrochioride; N-[2,3 ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-4-( 1 -naphthalenylcarbonyl)- 1 H- 1,4- benzodiazepin-8-yl] -3 -furancarboxamide, dihydrochioride; 7-(3-Chlorophenyl)-2,3 ,4,5-tetrahydro-l1-(1 H-imidazol-4-ylmethyi)-4-( 1- naphthalenylcarbonyl)- 1 H-I ,4-benzodiazepine, dihydrochioride; 2-Methyl-N-[2,3 ,4,5-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-4-(lI-naphthalenylcarbonyl)- 1H- 1 ,4-benzodiazepin-8-yl]benzamide, dihydrochioride; N-Phenyl-N'-[2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-4-( 1 -naphthalenylcarbonyl)- 1 H- I ,4-benzodiazepin-8-yI] urea, d ihydrochloride; 2,3 ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-4-( I -naphthalenylcarbonyl)-7-(3-pyridinyl)- 1 H-I ,4-benzodiazepine, trihydrochioride; 2,3 ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-9-methoxy-4-( 1 -naphthalenylcarbonyl)- 1 H- I ,4-diazepine, dihydrochioride; (R)-2,3,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-3-[2-(methylthio)ethyl]-4-( I- naphthalenylcarbonyl)- 1 H-I ,4-benzodiazepine, hydrochloride; 2,3 ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-4-( I -naphthalenylcarbonyl)-3 -(phenylmethyl)- 1 H-I ,4-benzodiazepine, hydrochloride; 2,3 ,4,5-Tetrahydro-3-(2-hydroxyethyl)- 1 H-imidazol-4-ylmethyl)-4-( 1- naphthalenylcarbonyl)- 1 H-I ,4-benzodiazepine, tri fluoroacetate; ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-4-( 1 -naphthalenylcarbonyl)-3- (phenylmethyl)-lIH-I ,4-benzodiazepine, tri fluoroacetate; 4-Acetyl-7-bromo-2,3,4,5-tetrahydro- I H-imidazol-4-ylmethyl)-3 -(phenylmethyl)- 1 H- 1,4- benzodiazepine, hydrochloride; o 7-Bromo- 1,2,3 ,5-tetrahydro-l1-(1 H-imidazol-4ylmethyl)-3-(phenylmethyl)-4H- 1,4- 00 benzodiazepine-4-carboxamide, trifluoroacetate; 7-Bromo-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-4-(methylsulfonyl)-3 -(phenylmethyl)- 1 H-I ,4-benzodiazepine, hydrochloride; 4-Acetyl-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-7-phenyl-3-(phenylmethyl)- I H- 1,4- benzodiazepine, trifluoroacetate; IND4-Acetyl-7-bromo-3 -[(4-chlorophenyl)methyl]-2,3 ,4,5 -tetrahydro- 1 H-imidazol-4-ylmethyl)- 1 H-I ,4-benzodiazepine, dihydrochioride; 4-Acetyl-2,3 ,4,5-tetrahydro- I H-imidazol-4-ylmethyl)-3-(phenylmethyl)- I H-naphtho[2,3-e]- I ,4-diazepine, monohydrochioride; N-Cyclohexyl-N'-[2,3 ,4,5-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-4-( 1-naphthalenylcarbonyl]- I H-i ,4-benzodiazepin-8-yl]urea, dihydrochioride; 2,3,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-4-(methylsulfonyl)-3-(phenylmethyl)- 1 H- naphtho -1 ,4-diazepine, monohydrochioride; 2,2-Dimethyl-N-[2,3,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-4-( I -naphthalenylcarbonyl)- 1 H-i ,4-benzodiazepin-8-yl]propanamide, dihydrochioride; 2,3 ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-4-( 1 -naphthalenylsulfonyl)-7-phenyl- 1 H- 1,4- benzodiazepine, monohydrochioride; 4-Acetyl-7-bromo-2,3,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-3-(2-naphthalenylmethyl)- I H-I ,4-benzodiazepine, dihydrochioride; 4-Acetyl-7-bromo-2,3,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-3-( I -naphthalenylmethyl)- 1 H-i ,4-benzodiazepine, dihydrochioride; 7-(2-Chlorophenyl)-2,3,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-4-( 1- naphthalenylcarbonyl)- 1 H-I ,4-benzodiazepine, dihydrochioride; 2,3 ,4,5-Tetrahydro- I H-imidazol-4-ylmethyl)-7-phenyl- I H-I ,4-benzodiazepine, monohydrochioride; 1 -Methyl-N-[2,3,4,5-tetrahydro- I H-imidazol-4-ylmethyl)-4-( 1 -naphthalenylcarbonyl)- 1 H- 1 ,4-benzodiazepin-8-yl]-2-piperidinecarboxamide, tri hydrochloride; N-[2,3 ,4,5-tetrahydro- I H-imidazol-4-ylmethyl)-4-( 1-naphthalenylcarbonyl)- I H- 1,4- benzodiazepin-8-yI]-4-morpholinecarboxamide, d ihydrochloride; 2,3 ,4,5-Tetrahydro- 1-(1 H-imidazol-4-ylmethyl)-4-( 1-naphthalenylcarbonyl)- 1 H- 1,4- benzodiazepin-8-yI]-3-methylbutanamide, dihydrochioride; 1,2,3 ,5-Tetrahydro- I H-imidazol-4-ylmethyl)-N,N,7-triphenyl-4H- 1 ,4-benzodiazepin carboxamide, dihydrochioride; o ~1 ,2,3,5-Tetrahydro-l1-(1 H-imidazoi-4-ylmethyl)-3-(phenylmethyl)-4H-naphtho[2,3-e]- 1,4- 00 diazepine-4carboxylic acid, methyl ester, monohydrochioride; 2,3 ,4,5-Tetrahydro-l1-(1 H-imidazoi-4-ylmethyl)-7-phenyl-4-[(4-phenyl-1I,2,3-thiadiazol-5- yl)carbonyl]- 1 H-i ,4-benzodiazepine, trifluoroacetate; 8 [(Cyc lohexylam ino)carbonyl] amino] -2,3,4,5 -tetrahydro- 1 H-imidazol-4-ylmethyl)-3- (phenylmethyl)- 1 H-i ,4-benzodiazepine-4-carboxylic acid, 1, 1 -dimethylethyl ester; 2,3 ,4,5-Tetrahydro- I H-imidazol-4-ylmethyl)-8- [[(4-methylphenyl)sulfonyljamino] -3 C) 10 (phenylmethyl)- 1 H-i ,4-benzodiazepine-4-carboxylic acid, 1, 1 -d imethyl ethyl ester; 7-Bromo- 1,2,3 ,4-tetrahydro- 1 H-imidazol-4-ylmethyl)-3 -(phenylmethyl)-5H- 1,4- di hydrochloride; 2,3,4,5-Tetrahydro-l1-(1 H-imidazol-4-yimethyl)-4-[ 1 -oxo-3-( 1-piperidinyl)propyl]-7-phenyl- 1 H-i ,4-benzodiazepine, trihydrochioride; 2,3 ,4,5-Tetrahydro-l1-(1 H-imidazoi-4-ylmethyl)-7-phenyl-4-(4-quinolinylcarbonyl)- 1 H- 1,4- benzodiazepine, trihydrochioride; 4-[(5-Bromo-3-pyridinyl)carbonyl]-2,3,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-7-phenyl- 1 H-i ,4-benzodiazepine, trihydrochioride; (S)-4-[2-(Dimethylamino)- 1 -oxo-3-phenylpropyl]-2,3 ,4,5-tetrahydro- 1 H-imidazol-4- ylmethyl)-7-phenyl- IH-i ,4-benzodiazepine, trihydrochioride; 2,3 ,4,5-Tetrahydro-4-[4-hydroxy-3-(4-morpholinyl-methyl)benzoyl]- 1 H-imidazol-4- ylmethyl)-7-phenyl- IH-I ,4-benzodiazepine, trihydrochioride; (S)-2,3,4,5-Tetrahydro- 1 H-imidazoi-4-ylmethyi)-4-[( I -methyl-2-pyrroiidinyl)carbonyi]-7- phenyl- 1 H-i ,4-benzodiazepine, trihydrochioride; 2,3 ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-7-phenyl-4-[[2-(propylthio)-3 pyridinyl]carbonyl] -1H-i ,4-benzodiazepine, tri hydrochloride; 4-[(2-Chloro-6-methyl-4-pyridinyl)carbonyl]-2,3,4,5-tetrahydro- 1 H-imidazol-4-ylmethyi)-7- phenyl- 1 H-i ,4-benzodiazepine, trihydrochioride; 2,3 ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-7-phenyl-4-[[2-(phenythio)-3 pyridinyl]carbonyl]-1 H-I ,4-benzodiazepine, trihydrochioride; 2,3 ,4,5-Tetrahydro- I H-imidazol-4-ylmethyl)-4-[[2-(4-methylphenoxy)-3- piperidinyl]carbonyl]-7-phenyl- 1 H-I ,4-benzodiazepine, tri hydrochloride; 2,3 ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-4-[(2-methoxy-3-pyridiny)carbonylJ-7-pheny- 1 H-i ,4-benzodiazepine, trihydrochioride; 2,3 ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-7-phenyl-4-[(5-phenyl-4-oxazolyl)carboiyl]- I H-i ,4-benzodiazepine, dihydrochioride; o 4-Acetyl-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-7-phenyl- I H-i ,4-benzodiazepine, 00 dihydrochloride; 2,3 ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-7-phenyl-4- [(tetrahydro-3 -furanyl)carbonyl] 1 H-I ,4-benzodiazepine, dihydrochioride; 2,3 ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-4-[(2-methoxyethoxy)acetyl]-7-phenyl- I H- 1,4- benzodiazepine, d ihydrochloride; IND2,3,4,5-Tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-4-(4-(4-morpholinylmethyl)benzoyl]-7 C) 10 2,3 ,4,5-Tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-4-(4-(4-morpholinylmethyl)benzoyl]-7 2,3 ,4,5-Tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-4-[4-(methylsulfonyl)benzoyl]-7-phenyl- IH- 1 ,4-benzodiazepine, d ihydrochloride; 2,3,4,5 -Tetrahydro- 1 H-imidazol-4-ylmethyl)-4- [1 -oxo-3 -(phenylsul fonyl)propyl] -7-phenyl- 1 H-i ,4-benzodiazepine, di hydrochloride; 2,3 ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-7-phenyl-4-(3-pyridinylacetyl)- I H- 1 ,4benzodiazepine, tri hydrochloride; 2,3 ,4,5-Tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-7-phenyl-4-(2-quinoxalinylcarbonyl)- 1 H- 1,4- benzodiazepine, tetrahydrochioride; 2,3,4,5-Tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-4-(4-isoquinolinylcarbonyl)-7-phenyl- IH- 1,4- 0 benzodiazepine, trihydrochioride; 4-[(2-Chloro-3-pyridinyl)carbonyl]-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-7-phenyl- I H-i ,4-benzodiazepine, tri hydrochloride; 2,3 ,4,5-Tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-7-phenyl-4-(3 -pyridinylcarbonyl)- 1 H- 1,4- benzodiazepine, tri hydrochloride; 4-[(2,6-Dimethoxy-3-pyridinyl)carbonyl]-2,3 ,4,5-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-7- phenyl- I H-i ,4-benzodiazepine, trihydrochioride; 2,3 ,4,5-Tetrahydro-lI-(I H-imidazol-4-ylmethyl)-7-phenyl-4-(2-pyrazinylcarbonyl)- 1H- 1,4- benzodiazepine, tetrahydrochioride; 4-(2-Ethoxybenzoyl)-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-7-phenyl- 1 H- 1,4- benzodiazepine, dihydrochioride; 4-[3-(Dimethylamino)benzoyl]-2,3 ,4,5-tetrahydro- 1-(1 H-imidazol-4-ylmethyl)-7-phenyl- IH- 1 ,4-benzodiazepine, trihydrochioride; 2,3 ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-7-phenyl-4-[( I -phenylcyclopropyl)carbonyl]- 1 H-I ,4-benzodiazepine, dihydrochloride; 4-[(Bicyclo[4.2. 0]octa-1I,3 ,5-trien-7-yl)carbonyl]-2,3,4,5-tetrahydro- 1-(1 H-imidazol-4- __ylmethyl)-7-phenyl- I H-I ,4-benzodiazepine, di hydrochloride; o 4-Benzoyl-2,3 ,4,5-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-7-phenyl- IH-i ,4-benzodiazepine, 00 di hydrochloride; 4-(2-Chlotobenzoyl)-2,3,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-7-phenyl- 1 H- 1,4- benzodiazepine, dihydrochioride; 4-(2,3 -D ichilorobenzoyl)-2,3,4,5 -tetrahydro- 1 H-imidazol-4-ylmethyl)-7-phenyl- 1 H- 1,4- benzodiazepine, dihydrochioride; N-[2-[[2,3,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-7-phenyl- 1 H-i ,4-benzodiazepin-4- C) 10 yl]carbonyl]phenyl]acetamide, dihydrochioride; 2,3 ,4,5-Tetrahydro-l1-(1 H-imidazol-4-ylmethyi)-4-(2-phenoxybenzoyl)-7-phenyl- 1 H- 1,4- benzodiazepine, di hydrochloride; 2,3 ,4,5-Tetrahydro- I H-imidazol-4-ylmethyl)-4-(2-methoxybenzoyl)-7-phenyl- I H- 1,4- benzodiazepine, di hydrochloride; 4-(2,3-Dimethoxybenzoyl)-2,3,4,5-tetrahydro- I H-imidazol-4-ylmethyl)-7-phenyl- 1 H- 1,4- benzodiazepine, di hydrochloride; 4-(2,4-Dimethoxybenzoyl)-2,3,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-7-phenyl- 1 H- 1,4- benzodiazepine, di hydrochloride; 4-(2,5-Dimethoxybenzoyl)-2,3,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-7-phenyl-I H- 1,4- benzodiazepine, dihydrochioride; 4-(2,6-Dimethoxybenzoyl)-2,3,4,5-tetrahydro- I H-imidazol-4-ylmethyl)-7-phenyl- I H- 1,4- benzodiazepine, di hydrochloride; 4-(2,3-Dihydroxybenzoyl)-2,3 ,4,5-tetrahydro-lI-(I H-imidazol-4-ylmethyl)-7-phenyl- 1 H- 1,4- benzodiazepine, dihydrochioride; 1,1 '-Biphenyl]-2-ylcarbonyl)-2,3 ,4,5-tetrahydro- 1 I H-imidazol-4-ylmethyl)-7-phenyl- I H- 1 ,4-benzodiazepine, dihydrochioride; 2,3 ,4,STetrahydro- 1 I H-imidazol-4-ylmethyl)-4-(2-methylbenzoyl)-7-phenyl- IH- 1,4- benzodiazepine, dihydrochioride; 4-(2,3-Dimethylbenzoyl)-2,3 ,4,5-tetrahydro- 1-(1 H-imidazol-4-ylmethyl)-7-phenyl- I H- 1,4- benzodiazepine, di hydrochloride; 4-(3-Cyanobenzoyl)-2,3 ,4,5-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-7-phenyl- 1 H- 1,4- benzodiazepine, d ihydrochloride; 4-(3-Chlorobenzoyl)-2,3 ,4,5-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-7-phenyl- 1 H- 1,4- benzodiazepine, dihydrochioride; 320 2,3 ,4,5-Tetrahydro- I H-imidazol-4-ylmethyl)-4-(3-phenoxybenzoyl)-7-phenyi- 1 H- 1,4- benzodiazepine, dihydrochioride; o 2,3 ,4,5-Tetrahydro-l1-(1 H-imidazol-4-ylmethyi)-4-(3-methoxybenzoyl)-7-phenyl-l1H- 1,4- 00 benzodiazepine, di hydrochloride; 4-(3 ,4-Dimethoxybenzoyl)-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-7-phenyl- 1 H- 1,4- benzodiazepine, dihydrochioride; 4-(3 ,5-Dimethoxybenzoyl)-2,3 ,4,5-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-7-phenyl- I H- 1,4- benzodiazepine, di hydrochloride; IND2,3 ,4,5-Tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-4-(3-methylbenzoyl)-7-pheny- 1 H- 1,4- benzodiazepine, d ihydrochloride; 1,2-Dioxo-2-phenylethyl)-2,3,4,5-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-7-phenyl- 1H- 1,4- benzodiazepine, d ihydrochloride; 4-[(2-Ethoxy- 1 -naphthalenyl)carbonyl]-2,3,4,5-tetrahydro- 1 H-imidazol-4-ylmethyi)-7- phenyl- 1 Hl-i ,4-benzodiazepine, dihydrochioride; 2,3 ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-4-(2-naphthalenylcarbonyl)-7-phenyl- 1 H- 1,4- benzodiazepine, di hydrochloride; 4-(Fluorophenylacetyl)-2,3,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-7-phenyi- 1H--1,4- benzodiazepine, dihydrochioride; 4-(Diphenylacetyl)-2,3 ,4,5-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-7-phenyl- I H- 1,4- benzodiazepine, dihydrochioride; 2,3 ,4,5-Tetrahydro-4-(2-hydroxy- 1-oxo-2-phenylpropyl)- 1-(1 H-imidazol-4-ylmethyl)-7-phenyl- 1 H-i ,4-benzodiazepine, dihydrochioride; 2,3 ,4,5-Tetrahydro-l1-(1 H-imidazol-4-yimethyl)-4-( 1H-indol-2-ylcarbonyl)-7-phenyl- I H- 1,4- benzodiazepine, dihydrochioride; 2,3 ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-4-( 1 H-indol-3-ylcarbonyl)-7-phenyl- 1 Hl- 1,4- benzodiazepine, dihydrochioride; 2,3 ,4,5-Tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-4-( IH-indoi-5-ylcarbonyl)-7-phenyl- 1 H- 1,4- benzodiazepine, di hydrochloride; 2,3 ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-4-[(1 -methyl- I H-indol-2-yl)carbonyl]-7- phenyl- 1 H-i ,4-benzodiazepine, dihydrochioride; 4-(2-Benzofuranylcarbonyl)-2,3,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-7-phenyl- I H-i ,4- benzodiazepine, dihydrochioride; 2,3,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyi)-7-phenyl-4-(3-pyridinylcarbonyl)- 1 H- 1,4- benzodiazepine, N-oxide, dihydrochioride; 2,3 ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-7-phenyl-4-(2-pyridinylcarbonyl)- I H- 1,4- benzodiazepine, trihydrochioride; o 2,3 ,4,5-Tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-7-phenyl-4-(2-quinolinylcarbonyl)- 1 H- 1,4- 00 benzodiazepine, trihydrochioride; 2,3 ,4,5-Tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-7-phenyl-4-( 1-isoquinolinylcarbonyl)- 1 H- 1,4- benzodiazepine, trihydrochioride; 4-(3-Chloro-2-nitrobenzoyl)-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-7-phenyl- 1 H- 1,4- benzodiazepine, dihydrochioride; 1-02,3 ,4,5-Tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-4-(2-nitrobenzoyl)-7-phenyl- 1 H- 1,4- benzodiazepine, dihydrochioride; 2,3 ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-4-(3-methoxy-2-nitrobenzoyl)-7-phenyl- 1 H- 1 ,4-benzodiazepine, dihydrochioride; 2,3,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-4-( I H-indol-4-ylcarbonyl)-7-phenyl- 1 H- 1,4- benzodiazepine, dihydrochioride; 4-[(2,6Dihydroxy-3-naphthalenyl)carbonyl]-2,3,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-7- phenyl- I H-I ,4-benzodiazepine, dihydrochioride; 4-(lI H-Benzimidazol-5-ylcarbonyl)-2,3,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-7-phenyl- I H-I ,4-benzodiazepine, tri hydrochloride; 1 H-Benzotriazol-5-ylcarbonyl)-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-7-phenyl- 1 H- ZO 1 ,4-benzodiazepine, di hydrochloride; 2,3,4,5-Tetrahydro-lI-(I H-imidazol-4-ylmethyl)-4-[(4-methoxy-2-quinolinyl)carbonyl]-7- phenyl- I Hl-I ,4-benzodiazepine trihydrochioride; ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-7-phenyl- 1 H-I ,4-benzodiazepin-4- yI]carbonyl]phenyl] -acetamide, dihydrochioride; 2,3 ,4,5-Tetrahydro-l1-( I H-imidazol-4-ylmethyl)-4-(2-methyl-l1-oxo-2-phenylpropyl)-7-phenyl- 1 H-I ,4-benzodiazepine, dihydrochioride; 4-[2-(Dimethylamino)benzoyl]-2,3,4,5-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-7-phenyl- 1 H- 1 ,4-benzodiazepine, trihydrochioride; 4-(3-Ethoxybenzoyl)-2,3 ,4,5-tetrahydro- 1-(1 H-imidazol-4-ylmethyl)-7-phenyl- 1H- 1,4- benzodiazepi ne,di hydrochloride; 2,3,4,5-Tetrahydro-4-(2-hydroxy[ 1 '-biphenyl]-3-ylcarbonyl)- 1-(1 H-imidazol-4-ylmethyl)-7- phenyl- 1 H-I ,4-benzodiazepine, di hydrochloride; 2,3 ,4,5-Tetrahydro-4-[2-[(2-hydroxyethyl)thio]benzoyl]- 1-(1 H-imidazol-4-ylmethyl)-7-phenyl- 1 H-i ,4-benzodiazepine, dihydrochioride; 2,3,4,5-Tetrahydro- I H-imidazol-4-ylmethyl)-4-[(2-methoxy- 1 -naphthalenyl)carbonyl]-7- phenyl- 1 H-i ,4-benzodiazepine, dihydrochloride; o 2,3,4,5-Tetrahydro-4-[(2-hydroxy-4-qiunolinyl)-carbonyl]- 1 H-imidazol-4-ylmethyl)-7- 00 phenyl- 1 H-i ,4-benzodiazepine, dihydrochioride; ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-7-phenyl- 1 H-I ,4-benzodiazepin-4- yl]carbonyl]benzamide, dihydrochloride; 1,1-Dimethylethyl)-2-[[2,3 ,4,5-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-7-phenyl- 1H- 1,4- benzodiazepin-4-yI]carbonyl]benzaniide, dihydrochioride; IDN-(4-Fluorophenyl)-N'-[3-[[2,3 ,4,5-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-7-phenyl- IH- 1,4- benzodiazepin-4-yl]carbonyl]phenyl]urea, dihydrochioride; 2,3,4,5-Tetrahydro- I H-imidazol-4-ylmethyl)-4-[(3-methyl-4-oxo-2-phenyl-4H-benzopyran- 8-yI)carbonyl]-7-phenyl- 1 H-i ,4-benzodiazepine, dihydrochioride; 2,3,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-7-phenyl-4-[3-(trifluoromethoxy)benzoyl]- I H- 1 ,4-benzodiazepine, di hydrochloride; 4-(2-Cyanobenzoyl)-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-7-phenyl- 1 H- 1,4- benzodiazepine,dihydrochloride; 2,3,4,5-Tetrahydro- I H-imidazol-4-ylmethyl)-4-[2-[[(4- methophenyl)sulfonyl]amino]benzoyl]-7-phenyl- 1H-I ,4-benzodiazepine, dihydrochioride; 2,3,4,5-Tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-7-phenyl-4-(6-quinolinylcarbonyl)- IH- 1,4- benzodiazepine, trihydrochioride; 2,3,4,5-Tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-7-phenyl-4-(8-quinolinylcarbonyl)- 1 H- 1,4- benzodiazepine, tri hydrochloride; 4-(Benzo[b]thiophen-2-ylcarbonyl)-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-7-phenyl- I H-i ,4-benzodiazepine, dihydrochioride; 4-[[4-(Dimethylamino)- I -naphthalenyl]-carbonyl] -2,3,4,5-tetrahydro- 1 H-imidazol-4- ylmethyl)-7-phenyl- I H-i ,4-benzodiazepine, tri hydrochloride; 2,3,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-7-phenyl-4-( I H-purin-6-ylcarbonyl)- 1 H- 1,4- benzodiazepine, trihydrochioride; 2,3,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-4-(methoxyphenylacetyl)-7-phenyl- 1 H- 1,4- benzodiazepine, di hydrochloride; 2,3,4,5-Tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-4- [(5-methyl-I -phenyl- IH-pyrazol-4- yl)carbonyl]-7-phenyl- I1 H-I,4-benzodiazepine,trihydrochloride; 2,3,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-4-[2-(2-methylphenyl)- I -oxopropyl]-7-phenyl- 1 Hl-I ,4-benzodiazepine, di hydrochloride; 323 2,3 ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-7-phenyl-4-[(tetrahydro-4-phenyl-2H-pyran-4- yl)carbonyl]- 1 H-i ,4-benzodiazepine, dihydrochioride; o 2,3,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-4-[2-(methylphenylamino)benzoyl]-7-phenyl- 00 1 H-i ,4-benzodiazepine, trihydrochioride; 2,3 ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-7-phenyl-4-(4quinolinylcarbonyl)- 1 H-phenyl- 1 H-i ,4-benzodiazepine, trihydrochioride; 2,3 ,4,5-Tetrahydro- I H-imidazoi-4-ylmethyl)-7-phenyl-4-(4-quinolinylcarbonyl)- 1 H- 1,4- benzodiazepine, N-oxide, dihydrochioride; IND N-Methyl-N-(2-pyridinylmethyl)-2-[[2,3,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-7-phenyl- C) 10 1 H-i ,4-benzodiazepin-4-yl]carbonyl]benzamide, trihydrochioride; 2,3 ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-4-(3-isoquinolinylcarbonyl)-7-phenyl- I H- 1,4- bezodiazepine, trihydrochioride; 2,3 ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-4-[(2-naphthalenylthio)acetyl]- 1 H- 1,4- benzodiazepine, trifluoroacetate ,4-Dimethoxyphenyl)- 1 -oxopropyl]-2,3 ,4,5-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)- 1 H- 1 ,4-benzodiazepine, trifluoroacetate 1,1'-Biphenyl]-4-ylacetyl)-2,3 ,4,5-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)- 1 H- 1,4- benzodiazepine, trifluoroacetate 2,3 ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-4-(2-naphthalenylacetyl)- 1 H- 1,4- benzodiazepine,trifluoroacetate 1,1'-Biphenyl]-2-ylcarbonyl)-2,3,4,5-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)- 1H- 1,4- benzodiazepine, trifluoroacetate 2,3,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-4-[(2-phenyl-4-quinolinyl)carbonyl]- 1H- 1,4- benzodiazepine, trifluoroacetate 2,3 ,4,5-Tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-4-(3-pyridinylacetyl)- 1 H-i ,4-benzodiazepine, trifluoroacetate 4-(9H-Fluoren-9-ylacetyl)-2,3 ,4,5-tetrahydro- I H-imidazol-4-yimethyl)- I H- 1,4- benzodiazepine, trifluoroacetate (S)-4-[2-(Dimethylamino)- 1 -oxo-3-phenylpropyl]-2,3 ,4,5-tetrahydro- 1 H-imidazol-4- ylmethyl)- 1 H-I ,4-benzodiazepine, trifluoroacetate ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-4-[(2-oxo-4-phenyl-3-oxazolidinyl)acetyl]- 1 H-I ,4-benzodiazepine, trifluoroacetate 4-(9-Acridinylcarbonyl)-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)- I H- 1,4- benzodiazepine, trifluoroacetate 2,3 ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-4-(3-phenoxybenzoyl)- 1 Hl-i ,4-benzodiazepine, trifluoroacetate 2,3 ,4,5-Tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-4-[[4'-(trifluoromethyl)L 1,1 -bipheriyl]-2- 00yl]carbonyl]- IH-I ,4-benzodiazepine, trifluoroacetate 2,3 ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-4-(4-phenoxybenzoyl)- 1 Hl-I ,4-benzodiazepine, trifluoroacetate 2,3,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-4-(2-naphthalenylcarbonyl)- 1 Hl- 1,4- benzodiazepine, trifluoroacetate IND 2,3 ,4,5-Tetrahydro- I H-imidazol-4-ylmethyl)-4-( I -oxo-4-phenylbutyl)- I Hl- 1,4- C) 10 benzodiazepine, trifluoroacetate 2,3 ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-4-[(2-phenoxyphenyl)acetyl]- 1 H- 1,4- benzodiazepine, trifluoroacetate 2,3 ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-4-[2-[(4-methylphenyl)sulfinyl]benzoyl]- 1 H- 1 ,4-benzodiazepine, trifluoroacetate 2,3 ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-4-[2-[(phenylmethyl)amino]benzoyl]- I H- 1,4- benzodiazepine, trifluoroacetate I ,2,3,5-Tetrahydro- 1 H-imidazol-4y1-methyl)-N,N-diphenyl-4H- I ,4-benzodiazepine- 4carboxamide, hydrochloride; 1,2,3 ,5-Tetrahydro- 1 H-imidazol-4-yl-methyl)-a,7-diphenyl-4H- I ,4-benzodiazepine-4-acetic acid, methyl ester, hydrochloride; 4-Acetyl-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-3-(phenylmethyl)- I Hl- 1,4- benzodiazepine, hydrochloride; (R)-7-Bromo-2,3,4,5-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-4-(methylsulfonyl)-3- (phenylmethyl)- IH-i ,4-benzodiazepine, hydrochloride; (R)-2,3,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-4-(methylsulfonyl)-3-(phenylmethyl)- I Hl- I ,4-benzodiazepine-7-carbonitrile, monohydrochioride; (R)-4-Acetyl-2,3,4,5-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-7-phenyl-3-(phenylmethyl)- 1H- 1 ,4-benzodiazepine, monohydrochioride; 7-Bromo-4-[[2-(dimethylamino)ethyl]sulfonyl]-2,3 ,4,5-tetrahydro- I H-imidazol-4-ylmethyl)- 3-(phenylmethyl)-4H-1 ,4-benzodiazepine, trifluoroacetate 2,3 ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-7-phenyl-4-[( 1,2,3 ,4-tetrahydro- I quinolinyl)carbonyl]- 1 H-i ,4-benzodiazepine, monohydrochioride; N-Ethyl- 1,2,3 ,5-tetrahydro- 1 H-irnidazol-4-ylmethyl)-N,7-diphenyl-4H- I ,4-benzodiazepine- 4-carboxamide, monohydrochloride; 325 4-[(2,3-Dihydro- 1 H-indol- 1 -yl)carbonyl]-2,3,4,5-tetrahydro- 1 H-imidazol-4-ylmethyi)-7- phenyl-l1H-I ,4-benzodiazepine, monohydrochloride; o 2,3 ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-4-(methylsulfonyl)-3-(phenylmethyl)-7-(4- 00 pyridinyl)- 1 H-I ,4-benzodiazepine, tri hydrochloride; (R)-4-[[2-(Dimethylamino)ethyl]sulfonyl]-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-7- phenyl-3 -(phenylmethyl)- 1 H-i ,4-benzodiazepine, trifluoroacetate [2,3 ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-4-( I -naphthalenylcarbonyl)- 1 H- 1,4- benzodiazepin-8-yllcarbamic acid, cyciohexyl ester, di hydrochloride; IND(R)-7-Bromo-2,3 ,4,5-tetrahydro-l1-(1-methyl-i H-imidazol-5-yl)methyl)-4-(methylsulfonyl)-3- C) 10 (phenylmethyl)- I H-i ,4-benzodiazepine, hydrochloride; (R)-7-Cyano-2,3 ,4,5-tetrahydro-lI-[(1-methyl-i H-imidazol-5-yl)methyl]-4-(methyisulfony)-3 (phenylmethyl)- I H-i ,4-benzodiazepine, monohydrochloride; 4-[2-(4-Chlorophenyl)-1I,2-dioxoethy]-2,3 ,4,5-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-7- phenyl- 1 H-i ,4-benzodiazepine, hydrochloride; 1,2-Dioxopropyl)-2,3 ,4,5-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-7-phenyl- 1H- 1,4- benzodiazepine, hydrochloride; 2,3 ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-4-[2-(4-nitrophenyl)- I ,2-dioxoethyl]-7-phenyl- I H-i ,4-benzodiazepine, hydrochloride; 2,3 ,4,5-Tetrahydro- 1 H-imidazoi-4-ylmethyl)-4-[2-(4-methoxyphenyl)-1I,2-dioxoethyl]-7- phenyl- 1 H-I ,4-benzodiazepine, hydrochloride; 2,3 ,4,5-Tetrahydro-l1-(1 H-imidazol-4-yimethyl)-7-phenyl-4-(3 ,3,3 -trifluoro-1I,2-dioxopropyl)- I H-i ,4-benzodiazepine, trifluoroacetate (R)-7-Bromo-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylacetyl)-4-(methylsulfonyl)-3 (phenylmethyl)-1I H-i ,4-benzodiazepine, monohydrochioride; (R)-7-Bromo-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylethyl)-4-(methylsulfonyl)-3- (phenylmethyl)- 1 H-i ,4-benzodiazepine, monohydrochloride; 8-[(Cyclohexylcarbonyl)amino]- 1,2,3 ,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-3- (phenylmethyl)-4H-1I,4-benzodiazepine-4-carboxylic acid, methyl ester, di hydrochloride; N-[2,3 ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyi)-4-( 1 -naphtha]lenyl carbonyl)- I Hl- 1,4- benzodiazepin-8-yi]- 1 -piperidinecarboxamide, dihydrochloride; (R)-7-Cyano- 1,2,3 ,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-3-(phenylmethyl)-4H- I ,4- benzodiazepine-4-carboxyl ic acid, ethyl ester, hydrochloride; N-[2,3 ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-4-(methylsulfonyl)-3 -(phenylmethyl)- I H- I ,4-benzodiazepin-8-yl]cyclohexanecarboxamide, di hydrochloride; (R)-7-Cyano-4-[[2-(dimethylamino)ethyl]sulfonyl]-2,3,4,5-tetrahydro- 1 H-imidazol-4- ylmethyl)-3-(phenylmethyl)-4H- 1,4-benzodiazepine, dihydrochioride; o (R)-7-Cyano-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-4-[[2-(4- 00 morpholinyl)ethyl]sulfonyl]-3-(phenylmethyl)-4H- 1,4-benzodiazepine, dihydrochioride; N-[2,3 ,4,5-Tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-4-(2-methoxy-3-methylbenzoyl)- IH- 1,4- benzodiazepin8-yl] cyclohexanecarboxamide, dihydrochioride; 8-[(Cyclohexylcarbonyl)amino]-2,3 ,4,5-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-N-phenyi- 1H- I ,4-benzodiazepine-4-carboxamide, dihydrochioride; N-[2,3,4,5-Tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-4-[(2-methylphenyl)sulfonyl]-I1H- 1,4- C) 10 benzodiazepin-8-yl]cyclohexanamide, dihydrochioride; N-[2,3 ,4,5-Tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-4-[(2-methoxyphenyl)carbonyl]- IH- 1,4- benzodiazepin-8-yI]cyclohexanamide, dihydrochioride; (R)-7-Cyano- 1,2,3,5-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-3 -(phenylmethyl)-4H- 1,4- benzodiazepine-4-sulfonic acid, ethyl ester, hydrochloride; (3 R)-7-Bromo-l1-[cyano( 1H-imidazol-4-yl)methyl]-2,3,4,5-tetrahydro-4-(methylsulfonyl)-3- (phenylmethyl)- I H-i ,4-benzodiazepine, monohydrochloride; 1 -[2-Amino- I H-imidazol-4-yl)ethyl]-2,3,4,5-tetrahydro4-(methylsulfonyl)-3- (phenylmethyl)- 1 H-i ,4-benzodiazepine, dihydrochloride; I imethylIamino)- 1 H-imidazol-4-yl)ethyl]-2,3 ,4,5-tetrahydro-4-(methylsulfonyl)- 3-(phenylmethyl)- IH-I ,4-benzodiazepine, d ihydrochloride; I -[2-Amino- I H-imidazol-4-yl)ethyl]-7-bromo-2,3 ,4,5-tetrahydro-4-(methylsulfonyl)-3- (phenylmethyl)- 1 H-i ,4-benzodiazepine, dihydrochloride; (3 1 -[2-(Dimethylamino)- I H-imidazol-4-yl)ethyl]-7-bromo-2,3 ,4,5-tetrahydro-4- (methylsulfonyl)-3-(phenylmethyl)- 1 H-I ,4-bcnzodiazepine, dihydrochloride; 7-Cyano- 1,3 ,4,5-tetrahydro- 1 -methyl- I H-imidazol-5-ylmethyl)-3 -(phenylmethyl)-4- (phenylsul fonyl)-2H- 1,4-benzodiazepin-2-one, monohydrochloride; 7-Cyano- 1 ,3,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-3-(phenylmethyl)-4-(phenylsufonyl)- 2H-1I,4-benzodiazepin-2-one, monohydrochioride; 7-Bromo-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-4-(methylsulfonyl)-3 -(2-phenylethyl)- 1 H-I ,4-benzodiazepine, dihydrochioride; 7-Bromo-3 -[(3-chlorophenyl)methyl]-2,3,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-4- (methylsulfonyl)- I H-i ,4-benzodiazepine, d ihydrochloride; (R)-7-Bromo-3-(cyclohexylmethyi)-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-4- (methylsulfonyl)- 1 H-I ,4-benzodiazepine, dihydrochloride; 327 7-Bromo-3 -[(2-chlorophenyl)methyl]-2,3,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-4- __(methylsulfonyl)- 1 H-i ,4-benzodiazepine, dihydrochioride; o (S)-7-Bromo-3-(cyclohexylmethyl)-2,3,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-4- 00 (methylsulfonyl)- I Hl-I ,4-benzodiazepine, dihydrochioride; 7-Bromo-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-3-[(4-methoxyphenyl)methyl]-4- (methylsulfonyl)- 1 H-i ,4-benzodiazepine, dihydrochioride; 4-Acetyl-7-bromo-3-[(2-chlorophenyl)methyl]-2,3,4,5-tetrahydro- I H-imidazol-4-ylmethyl)- 1 H-i ,4-benzodiazepine, di hydrochloride; IND4-Acetyl-7-bromo-3-[(3-chlorophenyl)methyl]-2,3,4,5-tetrahydro- I H-irnidazoi-4-ylrnethyl)- 1iH-1,4-benzodiazepine, dihydrochioride; 7-Bromo-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-3-[(4-hydroxyphenyl)methyl]-4- (methylsulfonyl)- 1 H-i ,4-benzodiazepine, dihydrochioride; ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-4-(methylsulfonyl)-7-phenyl-3-(3- pyridinylmethyl)- I H-i ,4-benzodiazepine, di hydrochloride; 2,3 ,4,5-Tetrahydro-8-(hydroxymethyl)- 1 H-imidazol-4-ylmethyl)-4-( I naphthalenyicarbonyl)- 1 H-I ,4-benzodiazepine, di hydrochloride; 2,3,4,5 -Tetrahydro- I H-imidazol-4-ylmethyl)-4-( 1 -naphthalenylcarbonyl)-8- (phenoxymethyl)- 1 H-i ,4-benzodiazepine, dihydrochioride; N-Cyclohexyl-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyi)-4-( 1 -naphthalenylcarbonyl)- 1 H- 1 ,4-benzodiazepine-8-carboxamide, dihydrochioride; N-(Cyciohexylmethyl)-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-4-( 1- naphthalenylcarbonyl)- I H-I ,4-benzodiazepine-8-carboxamide, dihydrochioride; 2,3,4,5 -Tetrahydro- I H-imidazol-4-ylmethyl)-4-( 1 -naphthalenylcarbonyl)-N-(phenyimethyl)- 1 H-i ,4-benzodiazepi ne-8-carboxamide, dihydrochioride; (R)-4-Acetyl-7-[2-[(dimethylamino)methyl]phenyl]-2,3,4,5-tetrahydro- I H-imidazol-4- ylmethyl)-3-(phenylmethyl)- I H-i ,4-benzodiazepine, dihydrochioride; (R)-4-Acetyl-7-cyano-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-3-(phenylmethyl)- 1 H- 1 ,4-benzodiazepine, monohydrochioride; (R)-7-Cyano-2,3 ,4,5-tetrahydro- 1-(1 H-imidazol-4-ylmethyl)-4-( 1-oxobutyl)-3-(phenylmethyi)- 1iH-i ,4-benzodiazepine, monohydrochioride; (R)-7-Cyano-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-4-(2-methyl- 1 -oxopropyi)-3- (phenyimethyl)- 1 H-i ,4-benzodiazepine, monohydrochioride; (R)-7-Cyano-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-yimethyl)-3-(phenylmethyl)-4-(2- pyridinylacetyl)- 1 H-i ,4-benzodiazepine, dihydrochioride; (R)-7-Cyano-2,3,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-3 -(phenylmethyl)-4-(2- thienylsulfonyl)- 1 H-I ,4-benzodiazepine, monohydrochioride; o (R)-7-Cyano-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-4-[( 1 -methylethyl)sulfonyl]-3- 00 (phenyimethyl)- 1 H-i ,4-benzodiazepine, monohydrochioride; (R)-7-Cyano-2,3 ,4,5-tetrahydro- 1 I H-imidazol-4-yimethyl)-3-(Phenylmethyl)-4- [(trifluoromethyl)sulfonyl]- 1H-I ,4-benzodiazepine, monohydrochioride; (R)-7-Bromo-2,3 ,4,5-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-3-(phenylmethyl)-4- (propylsuifonyl)- 1 H-i ,4-benzodiazepine, monohydrochioride; (R)-7-Bromo-2,3 ,4,5-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-3-(phenylmethyl)-4- (phenylsul fonyl)- IH-I ,4-benzodiazepine, monohydrochioride; (R)-2,3,4,5-Tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-7-phenyl-3-(phenylmethyl)-4- (phenylsul fonyl)- I H-i ,4-benzodiazepine, monohydrochioride; (R)-2,3,4,5-Tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-7-phenyl-3 -(phenylmethyl)-4- (propylsulfonyl)- 1 H-i ,4-benzodiazepine, monohydrochioride; (R)-7-Cyano-4-[(4-fluorophenyl)suifonyl]-2,3,4,5-tetrahydro- 1-(1 H-imidazol-4-ylmethyl)-3- (phenylmethyl)- 1 H-I ,4-benzodiazepine, monohydrochioride; (R)-7-Cyano-4-[(3-cyanophenyl)sulfony]-2,3 ,4,5-tetrahydro-l1-( IH-imidazol-4-ylmethyl)-3- (phenylmethyl)- 1 H-i ,4-benzodiazepine, monohydrochioride; (R)-7-Cyano-2,3 ,4,5-tetrahydro- 1-(1 H-imidazol-4-ylmethyl)-4-[( 1-methyl-I H-imidazol-2- yl)sulfonyl]-3 -(phenylmethyl)- 1H-i ,4-benzodiazepine, dihydrochioride; (R)-4-[(3-Bromophenyl)sulfonyl]-7cyano-2,3 ,4,5-tetrahydro-l1-( IH-imidazol-4-ylmethyl)-3- (phenylmethyl)- I H-i ,4-benzodiazepine, monohydrochioride; (R)-N-[5-[[7-cyano-2,3 ,4,5-tetrahydro-l1-( IH-imidazoi-4-ylmethyl)-3-(phenylmethyl)- 1H- 1,4- benzodiazepin-4-yI]sulfonyl]-4-methyl-2-thiazolyl]acetamide, dihydrochioride; 4-Acetyl-2,3 ,4,5-tetrahydro-l1-( IH-imidazol-4-ylmethyl)-3-(phenylmethyl)-7-(4-pyridinyl)- 1H- 1 ,4-benzodiazepine, tri hydrochloride; 2,3 ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-4-(2-phenyl- 1 ,2-dioxoethyl)-7-(4-pyridinyl)- 1 H-i ,4-benzodiazepine, trihydrochioride; 2,3 ,4,5-Tetrahydro- I H-imidazol-4-ylmethyl)-7-(4-pyridinyl)-4-[2- (tri fluoromethoxy)benzoyl] -1 H-i ,4-benzodiazepine, trihydrochioride; ,4,5-Tetrahydro- I -+(1-methyl- I H-imidazol-5-yl)methyl]-4-(methylsulfonyl)-7-phenyl-3 (phenylmethyl)- 1 H-I ,4-benzodiazepine; (R)-7-Cyano-2,3 ,4,5-tetrahydro- I H-imidazol-4-ylmethyl)-4-(phenylacetyl)-3- (phenylmethyl)- 1 H-i ,4-benzodiazepine, monohydrochioride; 4-(2-Benzothiazolyl)-2,3,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-7-phenyl- 1 H- 1,4- benzazepine, trihydrochioride; o 2,3 ,4,5-Tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-3-(phenylmethyl)-7-(3-pyridinyl)-4- 00 (trifluoroacetyl)-l1H-I ,4-benzodiazepine, tri hydrochloride; 2,3 ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-4-(methylsulfonyl)-3-(phenylmethyl)-7-(3- pyridinyl)- I H-i ,4-benzodiazepine, trihydrochioride; 7-Bromo-3-[(1,1I -dimethylethoxy)methyl]- 1 ,2,3,4-tetrahydro- 1 I ,4-benzod iazepin-5 one; IND7-Bromo-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-4-(methylsulfonyl)-3 C) 10 (phenoxymethyl)- I H-i ,4-benzodiazepine, dihydrochioride; 7-Bromo-2,3,4,5-tetrahydro-3-(hydroxymethyl)- 1 H-imidazol-4-ylmethyl)-4- (methyisulfonyl)- I H-i ,4-benzodiazepine, monohydrochioride; 7-Bromo-3 -[1,1I -dimethylethoxy)methyl]-2,3 ,4,5-tetrahydro- I H-imidazol-4-ylmethyl)-4- (methyisul fonyl)- 1 H-i ,4-benzodiazepine; [7-Bromo-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-3 -(phenylmethyl)- 1 H- 1,4- benzodiazepin-8-yljcarbamic acid, 2-methyipropyl ester, trihydrochioride; [4-Acetyl-7-bromo-2,3 ,4 ,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-3 -(phenylmethyl)- 1 H- 1,4- benzodiazepin-8-yl]carbamic acid, 2-methyipropyl ester; N-[4-Acetyl-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-3-(phenylrnethyl)- I H-i 1,4- benzodiazepin-8-yl]cyclohexanecarboxamide, dihydrochioride; [7-Bromo-2,3,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-4-(methylsulfonyi)-3- (phenylmethyl)- 1 H-i ,4-benzodiazepin-8-yllcarbamic acid, 2-methyipropyl ester; ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-4-(phenylsulfonyl)-3-(phenylmethyl)- I H- 1 ,4-benzodiazepine-7-carbonitrile, monohydrochioride; 7-Bromo-1I,2,3 ,5-tetrahydro-lI-(I H-imidazol-4-ylmethyl)-3 -(phenylmethyl)-4H- 1,4- benzodiazepine-4-acetarnide; 7-Bromo-4-[(dimethylamino)acetyl]-2,3 ,4,5-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-3- (phenyimethyl)- I H-i ,4-benzodiazepine; (R)-7-Bromo-4-( 1,2-dioxopropyl)-2,3 ,4,5 -tetrahydro- I H-imidazol-4-ylmethyl)-3 (phenylmethyl)- IH-i ,4-benzodiazepine, trifluoroacetate; (R)-7-Bromo-4-(cyclopropylcarbonyl)-2,3,4,5 -tetrahydro- I H-imidazol-4-ylmethyl)-3 (phenylmethyl)- I H-i ,4-benzodiazepine, trifluoroacetate; (R)-7-Cyano-2,3 ,4,5 -tetrahydro- 1 H-imidazol-4-ylmethyl)-3-(phenylmethy!)-4- (propylsulfonyl)- I H-i ,4-benzodiazepine, monohydrochioride; 330 7-Bromo-2,3,4,5-tetrahydro- 1 ,4-bis( 1 H-imidazol-4-ylmethyl)-3 -(phenylmethyl)- 1 H- 1,4- __benzodiazepine, dihydrochioride; o 7-Bromo- 1,2,3 ,5-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-N,N-dimethyl-3-(phenylmethyl)-4H- 00 1 ,4-benzodiazepine-4-sulfonamide, monohydrochioride; 2,3 ,4,5-Tetrahydro- 1 H-imidazoi-4-ylmethyl)-4-(methylsulfonyi)-3-(phenylmethyl)- 1 H- 1,4- benzodiazepine-7-carbonitri le, monohydrochioride; (R)-7-Cyano- 1,2,3 ,5-tetrahydro- 1-(1 H-imidazol-4-yimethyl)-N,N-dimethyl-3-(phenylmethyl)- 4H-- 1 ,4-benzodiazepine-4-carboxamide monohydrochioride; 1-0N,N-Diethyl-2,3 ,4,5-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-4-(methylsulfonyl)-3 (phenylmethyl)- 1 H-i ,4-benzodiazepine-7-carboxamide, monohydrochioride; 2,3 ,4,5-Tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-7-phenyl-4-( 1-phenyl- I H-tetrazol-5-yl)- IH- I ,4-benzodiazepine, monohydrochioride; (R)-7-Cyano-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-3-(phenylmethyl)-4-(2- pyrazinylcarbonyl)-4H- 1,4-benzodiazepine, monohydrochioride; (R)-4-[7-Bromo-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-3-(phenylmethyl)-4H- 1,4- benzodiazepin-4-yI]-4-oxobutanoic acid, methyl ester, monohydrochioride; (R)-7-Cyano-2,3,4,5-tetrahydro- I H-imidazol-4-ylmethyl)-4-(4-morpholinocarbonyl)-3- (phenylmethyl)- 1 H-I ,4-benzodiazepine, monohydrochioride; (R)-7-Cyano-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-3-(phenylmethyl)-4-[[2-( 1- pyrrolidinyl)ethyl]sulfonyl]- 1H-i ,4-benzodiazepine, dihydrochioride; ,4,5-Tetrahydro- I H-imidazol-4-ylmethyl)-4-(methylsulfonyl)-7-phenyl-3-(3- pyridinylmethyl)- 1 H-i ,4-benzodiazepine, dihydrochioride; ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-7-phenyl-3-(3-pyridinylmethyl)-4-(2- thienylsulfonyl)- I H-i ,4-benzodiazepine, dihydrochioride; ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-7-phenyl-4-(propylsulfonyl)-3 pyridinylmethyl)- 1 H-i ,4-benzodiazepine, monohydrochioride; (R)-7-Bromo-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-4-(methylsulfonyl)-3 pyridinylmethyl)- I H-i ,4-benzodiazepine, monohydrochioride; 2,3 ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-4-(methylsulfonyl)-3 -(phenylmethyl)-7-(2- pyrimidinyl)- I H-i ,4-benzodiazepine,d ihydrochloride; (R)-7-Bromo-2,3 ,4,5-tetrahydro- I H-imidazol-4-ylmethyl)-3-(phenylmethyl)-4- [(trifluoromethyl)sulfonyl]- I H-i ,4-benzodiazepine, monohydrochioride; ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-7-phenyl-3-(phenylmethyl)-4- (trifluoroacetyl)- I H-i ,4-benzodiazepine, monohydrochioride; (R)-2,3,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-4-(methylsulfonyl)-3 -(phenylmethyl)-7-(4- pyridinyl)- I H-i ,4-benzodiazepine, dihydrochioride; o (R)-2,3,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-3-(phenylmethyl)-7-(4-pyridinyl)-4-(2- 00 thienylsulfonyl)- 1 H-I ,4-benzodiazepine, dihydrochioride; ,4,5-Tetrahydro 1 I H-imidazol-4-ylmethyl)-3-(phenylmethyl)-4-(phenylsufonyl)-7-(4- pyridinyl)- 1 H-i ,4-benzodiazepine, dihydrochioride; C ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-3-(phenylmethyl)-4-(propylsulfonyl)-7-(4- pyridinyl- I Hl-i ,4-benzodiazepine, dihydrochioride; (R)-7-Cyano-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-yimethyl)-3 -(phenylmethyl)-4-[(3 dimethyl-isoxazol-4-yl)sulfonyl]-I H-i ,4-benzodiazepine, dihydrochioride; (R)-7-Cyano4[(4-cyanophenyl)sulfonyl]-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-3- (phenylmethyl)- I H-I ,4-benzodiazepine, dihydrochioride; (R)-7-Cyano-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-3-(phenylmethyl)-4-[(2,2,2- tritluoroethyl)sulfonyl]- 1 H-i ,4-benzodiazepine, d ihydrochloride; (R)-[(5-Bromo-2-thienyi)sulfonyl]-7-cyano-2,3 ,4,5-tetrahydro- I H-imidazol-4-ylmethyl)-3- (phenylmethyl)- 1 H-i ,4-benzodiazepine, dihydrochioride; (R)-7-Cyano-2,3,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-4-[(4-methoxyphenyl)sulfonyl]-3- (phenylmethyl)- I H-i ,4-benzodiazepine, dihydrochioride; N-[[7-Bromo-2,3,4,5-tetrahydro- I H-imidazol-4-ylmethyl)-4-(methylsulfonyl)- I H-i 1,4- benzodiazepin-3 -ylmethyl] benzamide, dihydrochioride; (R)-7-Cyano- 1,2,3 ,5-tetrahydro-l1-(1 H-imidazoi-4-ylmethyl)-N,N-dimethyl-3-(phenylmethyl)- 4H- 1,4-benzodiazepine-4-sulfonamide, hydrochloride; (R)-7-Cyano- 1,2,3 ,5-tetrahydro-N,N-dimethyl-lI-[(I-methyl-i H-imidazol-5-yl)methyl]-3- (phenylmethyl)-4H-1I,4-benzodiazepine-4-sulfonamide, hydrochloride; (R)-7-Chloro-2,3 ,4,5-tetrahydro- 1 -[(I1-methyl- I H-imidazol-5-yl)methyl]-4-(methylsulfonyl)-3- (phenylmethyl)-1IH 1,4-benzodiazepine, monohydrochioride; (R)-7-Chloro-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-4-(methylsulfonyl)-3- (phenylmethyl)- 1 H-I ,4-benzodiazepine, monohydrochioride; (R)-7-Chloro-2,3 ,4,5-tetrahydro- 1 -+(1-methyl- I H-imidazol-5-yl)methyl]-4-(phenylsulfonyl)-3- phenylmethyl)- 1 H-i ,4-benzodiazepine, monohydrochloride; (R)-7-Cyano-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-yimethyl)-3-(pyridin-3 -ylmethyl)-4- (methylsul fonyl)- I H-i ,4-benzodiazepine, tetrahydrochloride; (R)-7-Bromo-2,3,4,5-tetrahydro- I H-imidazoi-2-ylmethyl)-4-(methylsulfonyl)-3 (phenylmethyl)- 1 H-i ,4-benzodiazepine, dihydrochloride; (R)-7-Bromo-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-4-[(l 1-methyl- I H-imidazo!-4- __yI)suifonyl] -3 -(phenylmethyl)- 1 H-i ,4-benzodiazepine, trihydrochioride; o (R)-7-Chloro-2,3 ,4,5-tetrahydro- 1 -methyl-imidazol-5-ylmethyl)-4-[(2-morphoin-4-y- 00 ethyl)sulfonyl]-3-(phenylmethyl)- 1 H-i ,4-benzodiazepine, dihydrochioride; (R)-7-Chloro-2,3,4,5-tetrahydro- 1 H-imidazoi-4-ylmethyl)-4-[(2-morpholin-4-yI- ethyl)sulfonyl]-3-(phenylmethyl)- 1 H-i ,4-benzodiazepine, dihydrochioride; (R)-7-Chloro-4-[(dimethylamino)suifonyi]- I -methyi- 1 H-imidazol-5-yI)methyl]-3- (phenylmethyl)- I H-I ,4-benzodiazepine, monohydrochioride; IND (R)-7-Chioro-2,3,4,5-tetrahydro- 1 -methyl-imidazoi-5-yimethyl)-4-[(4-methyl-piperidin-4-yl- C) 10 ethyl)sulfonyl]-3-(phenylmethyl)- I H-I ,4-benzodiazepine, dihydrochioride; (R)-7-Bromo-2,3 ,4,5-tetrahydro- I -methyl-imidazol-5-yimethyl)-4-[(4-methyl-piperidin-4-yl- ethyl)sulfonyl]-3-(phenylmethyl)- I H-I ,4-benzodiazepine, dihydrochioride; (R)-7-Cyano- 1,2,3 ,5-tetrahydro- 1 H-imidazoi-4-yimethyi)-3-(phenylmethyl)-41- 1,4- benzodiazepine-4-carboxyl ic acid, isopropyl ester, hydrochloride; (R)-7-Bromo-2,3 ,4,5-tetrahydro-4-[[2-( 1 H-imidazoi- I -yl)ethyl]sulfonyl]- 1 I H-imidazol-4- ylmethyl)-3 -(phenylmethyl)- 1 H-i ,4-benzodiazepine, dihydrochioride; (R)-7-Cyano-2,3 ,4,5-tetrahydro- I H-imidazol-4-ylmethyl)-4-(propylsulfonyl)-3 pyridinylmethyl)- 1 H-i ,4-benzodiazepine, hydrochloride; 7-Bromo-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-3-(phenylmethyl)- 1 H- 1,4- benzodiazepin-5 -one, hydrochloride; (R)-7-Bromo-2,3 ,4,5-tetrahydro-l1-(1 H-imidazol-1I-ylacetyl)-4-(methylsulfonyl)-3- (phenylmethyl)- 1 H- I ,4-benzodiazepine, trifluoroacetate; 1 ,2,4,5-Tetrahydro-l1-(1 H-imidazol-4-yimethyl)-2-(2-phenyiethyl)-3 H-I ,4-benzodiazepin-3- one; 2,3 ,4,5 -Tetrahydro- I H-imidazol-4-ylmethyl)-4-(methylsul fonyl)-2-(2-phenyl ethyl)- I H- 1,4- benzodiazepine, monohydrochioride; ,4,5-Tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-4-(methylsulfonyl)-7-phenyl-3 pyridinylmethyl)- 1 H-i ,4-benzodiazepine, dihydrochioride; (R)-2,3,4,5-Tetrahydro-l1-(1 H-imidazol-2-yimethyl)-4-(phenylsulfonyl)-3-(phenylmethyl)- 1H- 1 ,4-benzodiazepine-7-carbonitrile, hydrochloride; (R)-7-Cyano- 1 ,2,3,5-tetrahydro- I H-imidazol-4-ylmethyl)-N,N-dimethyl-3-(3- pyridinylmethyi)-4H-1i,4-benzodiazepine-4-carboxamide, dihydrochloridc; (R)-7-Cyano- 1 ,2,3,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-N,N-dimethyl-3-(3- pyridinylmethyl)-4H-1I,4-benzodiazepine-4-sulfonamide, dihydrochioride; ,4,5-Tetrahydro- 1 -(4cyanophenylmethyl)-imidazol-5ylmethyl)-4-(methylsulfonyl)-3 (phenylmethyl)- I H-i ,4-benzodiazepine-7-carbonitrile, hydrochloride; o (R)-2,3,4,5-Tetrahydro- 1 -(4-cyanophenylmethyi)-imidazol-4-ylmethyl)-4-(methylsulfonyl)- 00 3phenylmethyl)- 1 H-i ,4-benzodiazepine-7-carbonitrile, hydrochloride; (R)-4-Benzoyl-7-Cyano-2,3,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-3-(phenylmethyl)- I H- 1 ,4-benzodiazepine, monohydrochioride; 10(R)-7-Cyano-2,3 ,4,5-tetrahydro-l1-[(1-methyl-I H-imidazol-5-yl)methyl]-3-(pyridin-3 yimethyl)-4-(methylsul fonyl)- I H-i ,4-benzodiazepine, di hydrochloride; (R)-7-Cyano-2,3 ,4,5-tetrahydro-lI-[(1-methyl-i H-imidazol-5-yl)methyl]-3 -(pyridin-3- ylmethyl)-4-(propylsulfonyl)- I H-I ,4-benzodiazepine, trihydrochloride; (R)-7-Cyano-2,3 ,4,5-tetrahydro-l1-[(1 H-imidazol-4-yl)methyl]-3-(pyridin-3-ylmethyl)-4- (phenylsulfonyl)- 1 H-I ,4-benzodiazepine, dihydrochloride; 2,3,4,5-Tetrahydro- I H-imidazol-4-ylmethyl)-4-(methylsulfonyl)-7-phenyl-3- (phenylmethyl)- I H-i ,4-benzodiazepine; 1,2,3 ,5-Tetrahydro- I I H-imidazoi-4-ylmethyl)-N-( 1 -naphthalenyl)-7-phenyl-4H- i ,4- benzodiazepine-4-carboxamide, monohydrochioride; (S)-7-Bromo-2,3 ,4,5-tetrahydro- i H-imidazol-4-ylmethyl)-4-(methylsulfonyl)-3 (phenylmethyl)- I H-I ,4-benzodiazepine, hydrochloride; N-[2,3 ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-4-(2,3 -dimethylbenzoyl)- I H- 1,4- benzodiazepin-8-yl]cyclohexanecarboxamide, dihydrochloride; (R)-7-Cyano-N-[2-(dimethylamino)ethyl]-2,3,4,5-tetrahydro- I H-imidazol-4-ylmethyl)-N- methyl-3-(phenylmethyl)- 1H-i ,4-benzodiazepine-4-carboxamide, trifluoroacetate 7-Bromo-2,3 ,4,5-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-4-(methylsulfonyl)-2-oxo-3- (phenylmethyl)- 1 H-i ,4-benzodiazepine, trifluoroacetate; (R)-7-Cyano-4-(2-furanylcarbonyl)-2,3,4,5-tetrahydro- I-(1 H-imidazol-4-ylmethyl)-3- (phenylmethyl)- I H-I ,4-benzodiazepine, trifluoroacetate 1); (R)-7-Cyano-2,3 ,4,5-tetrahydro-l1-( IH-imidazol-4-ylmethyl)-4-[(4-nitrophenyl)sulfonyl]-3- (phenylmethyl)- I H-i ,4-benzodiazepine, trifluoroacetate; (R)-7-Cyano-2,3 ,4,5-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-4-[[4-(4-methyl- 1- piperazin)phenyl]sulfonyl]-3-(phenylmethyl)- I H-I ,4-benzodiazepine, trifluoroacetate; (R)-7-Cyano-2,3 ,4,5-tetrahydro-l1-( IH-imidazol-4-ylmethyl)-4-[[(4- dimethyiamino)phenyl] sulfonyl]-3-(phenylmethyi)- IH-i ,4-benzodiazepine, trifluoroacetate; (R)-7-Bromo-4-[[2-(dimethylam-ino)ethyl]sulfonyl]-2,3,4,5-tetrahydro- I H-imidazol-4- ylmethyl)-3-(phenylmethyi)-4H-1I,4-benzodiazepine, di hydrochloride; (R)-7-Cyano-2,3 ,4,5-tetrahydro- I H-imidazol-4-ylmethyl)-3-(phenylmethyl)-4-(3- pyridinylsulfonyl)- 1 H-i ,4-benzodiazepine, trihydrochioride; o 2,3 ,4,5-Tetrahydro- 1 H-imidazol-4-ylmethyl)-4-(methylsulfonyl)-3-(phenylmethyl)- 1 H- 1,4- 00 benzo-diazepine, dihydrochioride; (R)-7-Bromo-2,3 ,4,5-tetrahydro-l1-[(1 -methyl-i H-imidazol-4-yI)methyl]-4-(methylsulfonyl)-3- (phenylmethyl)- 1 H-I ,4-benzodiazepine, dihydrochioride; (R)-4-[[3-(Dimethylamino)propyl]sulfonyl]-2,3,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-7- phenyl-3-(phenylmethyl)- IH-I ,4-benzodiazepine, dihydrochioride; (R)-7-Cyano-2,3,4,5-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-3 -(phenylmethyl)- IH- 1,4- benzodiazepine, trihydrochloride; 4-Butyl-2,3,4,5-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-3-(Phenylmethyl)- I H- 1,4- benzodiazepine, trihydrochioride; (R)-7-Bromo-2,3 ,4,5-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-4-[[2-(4- morpholinyl)ethyl]sulfonyl]-3-(phenylmethyl)- 1 H-i ,4-benzodiazepine, dihydrochioride; (R)-7-lBromo-2,3 ,4,5-tetrahydro-l1-[(1-methyl-I H-imidazol-5-yl)methyl]-4- morpholinyl)ethyl]sulfonyl]-3 -(phenylmethyl)- 1H-I ,4-benzodiazepine, dihydrochioride; (R)-7-Cyano-l1-( IH-imidazol-4-ylmethyl)-4-(4-morpholinylsulfonyl)-3-(phenylmethyl)- IH- 1,4- benzodiazepine, monohydrochioride; (R)-7-Cyano-l1-[(1-methyl-I H-imidazol-5-yI)methyl]-4-[(4-morpholinyl)sulfonyl-]-3- (phenylmethyl)- 1 H-i ,4-benzodiazepine, monohydrochioride; (R)-7-Cyano-2,3 ,4,5-tetrahydro-l1-( IH-imidazol-4-ylmethyl)-4-[(4-aminophenyl)sulfonyl]-3- (phenylmethyl)- I H-I ,4-benzodiazepine, hydrochloride; 2,3,4,5-Tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-4-[(4-pyridylthio)acetyl]-7-phenyl- 1H- 1,4- benzodiazepine, di hydrochloride; N-(4-Chlorophenyl)-N'-cyano- 1,2,3,5-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-7-phenyl-4H- 1,4- benzodiazepine-4-imidamide, monohydrochloride; 4-Acetyl-7-bromo- 1,2,4,5,1 ',3'-hexahydro-l1-(1 H-imidazol-4-ylmethyl)spiro [3H- 1,4- benzodiazepine-3,2'-[2H]indene], d ihydrochloride; 7-Bromo-4- [3 -(di methyl amino)- 1 -oxopropyl]-2,3 ,4,5 -tetrahydro- 1 H im idazol-4-yl methyl)- 3-(phenylmethyl)- 1H-i ,4-benzodiazepine, trifluoroacetate ,4,5-Tetrahydro- I-(1-methyl-I H-imidazol-5-ylmethyl)-4-(phenylsulfonyl)-3- (phenylmethyl)- I H-i ,4-benzodiazepine-7-carbonitrile, monohydrochioride; 335 2,3 ,4,5-Tetrahydro- 1 -[(I1-methyl- I H-imidazol-5-yI)-methyl]-4-(methyl-sulfonyl)-7-phenyl-3 (pyridin-3-yI-methyl)- I H-i ,4-benzodiazepine, hydrochloride trifluoroacetate (1:0.75) salt; 00 4-[4-(Fluorophenyl)sulfonyl]-2,3 ,4,5-tetrahydro- I H-imidazolI-4-ylmethylI)-2-(2-phenyl ethyl)- 1 H-I ,4-benzodiazepine, monohydrochioride; 7-Bromo-2,3 ,4,5 -tetrahydro- 1 H-imidazol-4-yl-methyl)-4-(methyl-sulfonyl)-2-(2- phenylethyl)- 1 H-i ,4-benzodiazepine, monohydrochioride; (R)-7-Cyano-2,3 ,4,5-tetrahydro- 1 -(I1-methyl- I H-imidazol-5-ylmethyl)-4-[[2-( 1- morpholinyl)ethyi]sulfonyl]-3-(phenyimethyl)- IH-i ,4-benzodiazepine, d ihydrochloride; (R)-7-Bromo-2,3,4,5-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-4-(methyl-sulfonyl)-3 bromophenylmethyl)- I H-i ,4-benzodiazepine, hydrochloride; (R)-7-Bromo-2,3,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-4-(methyl-sulfonyl)-3-(thiazol-4- ylmethyl)- 1 H-I ,4-benzodiazepine, hydrochloride; (R)-7-Bromo-2,3,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-4-(propyl-sulfonyl)-3 -(thiazol-4- ylmethyl)- 1 H-i ,4-benzodiazepine, hydrochloride; (R)-7-Bromo-2,3,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-4-(propylsulfonyl)-3-(4- bromophenylmethyl)- I H-i ,4-benzodiazepine, hydrochloride; (R)-7-Bromo-2,3,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-3-(pyridin-3 -ylmethyl)-4- (methylsulfonyl)- 1 H-i ,4-benzodiazepine, trihydrochloride;, (R)-7-Bromo-2,3,4,5-tetrahydro- 1 H- I -methyl-imidazol-5-ylmethyl)-3-(pyridin-3 -ylmethyl)- 4-(methylsulfonyl)- 1 H-i ,4-benzodiazepine, dihydrochloride; (R)-7-Cyano-2,3,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-4-(phenyl-sulfonyl)-3-(4- cyanophenylmethyl)- IH-i ,4-benzodiazepine, hydrochloride; (R)-7-Cyano-4-[(N-methyl-N-phenylmethyl)aminosulfonyl]- 1 I H-imidazol-4-yl)methyi]-3- (phenylmethyl)- I H-i ,4-benzodiazepine, monohydrochloride; (R)-7-Cyano4-[N-(tetrahydroisoquinoline)sulfonyl]- 1 I H-imidazol-4-yl)methyl]-3- (phenylmethyl)- IH-i ,4-benzodiazepine, monohydrochloride; (R)-7-Cyano-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-4-(phenylsulfonyl)-3 thienylmethyl)- I H-i ,4-benzodiazepine, hydrochloride; cis-2,3 ,4,5-Tetrahydro- 1 ,5-bis( I H-imidazoi-4-yimethyl)-3-(phenylmethyl)- 1 H- benzodiazepine-2-carboxylic acid ethyl ester-trifluoroacetate (R)-7-Cyano4-[(N-piperidinyl)sulfonyi]- 1 H-imidazol-4-yl)methyl]-3-(phenylmethyl)- 1 H- 1 ,4-benzodiazepine, monohydrochioride; 336 (R)-7-Cyano-2,3 ,4,5-tetrahydro- 1 H- I -methyl-imidazol-5-ylmethyl)-3-(phenylmethyl)-4-(2- thienylsulfonyl)- 1 H-i ,4-benzodiazepine, hydrochloride; o (R)-7-Cyano-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-3-(pyridin-3-ylmethyl)-4-[[2- 00 (dimethylamino)ethyl]sulfonyI]- 1H-I ,4-benzodiazepine, tri hydrochloride; (R)-7-Cyano-2,3 ,4,5-tetrahydro-l1-(1 H-i -methyl-imidazol-5-yimethyl)-3-(phenylmethyl)-4- (propylsulfonyl)- 1 H-i ,4-benzodiazepine, hydrochloride; N-(Cyano)-N'-methyl- 1,2,3 ,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-7-phenyl-4H- 1,4- benzodiazepine-4-imidamide, hydrochloride; (R)-7-Cyano-4-[(2-nitrophenyl)-sulfonyl]-2,3 ,4,5-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-3- (phenyl-methyl)- I H-i ,4-benzodiazepine, hydrochloride; (R)-7-Cyano-4-[(4-methyl-phenyl)sulfonyl]-2,3 ,4,5-tetrahydro- I I H-imidazol-4-ylmethyl)-3- (phenylmethyl)- 1 H-i ,4-benzodiazepine, hydrochloride; (R)-7-Cyano4-(butylsulfonyl)-2,3,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-3 (phenylmethyl)- 1 H-i ,4-benzodiazepine, hydrochloride; (R)-7-Cyano-4-[(2-trifluoro-methylphenyl)sulfonyl]-2,3 ,4,5-tetrahydro- I H-imidazol-4- ylmethyl)-3 -(phenylmethyl)- I H-I ,4-benzodiazepine, hydrochloride; (R)-7-Cyano-4-[(2-trifluoromethyiphenyl)sulfonyl]-2,3 ,4,5-tetrahydro- I H-imidazol-4- ylmethyl)-3-(phenylmethyl)- 1 H-I ,4-benzodiazepine, hydrochloride; (R)-7-Cyano-4-[(2-methoxy-carbonylphenyl)sulfonyl]-2,3 ,4,5-tetrahydro- 1 H-imidazol-4- ylmethyl)-3-(phenylmethyl)- 1 H-I ,4-benzodiazepine, hydrochloride; (R)-7-Cyano-4-[(2-methyl-sulfonylphenyl)sulfonyl]-2,3,4,5-tetrahydro- 1 H-imidazol-4- ylmethyl)-3 -(phenylmethyl)- 1 H-I ,4-benzodiazepine, hydrochloride; (R)-7-Cyano-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-yimethyl)-3 -(phenylmethyl)-4-(((4- methylnonyl)-phenyl)-suifonyl)- I H-i ,4-benzodiazepine; (R)-7-Cyano-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-3 -(phenylmethyl)-4-(((4- trifluoromethyl)-phenyl)-sulfonyl)- I H-I ,4-benzodiazepine; (R)-7-Cyano-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-3 -(phenylmethyl)-4-((3 methoxypropyl)-sulfonyl)- 1 H-i ,4-benzodiazepine; (R)-7-Cyano-2,3 ,4,5-tetrahydro- 1 I H-imidazol-4-ylmethyl)-3-(phenylmethyl)-4-((3 ,4- dimethoxyphenyl)-sulfonyl)-1I H- 1,4-benzodiazepine; (R)-7-Cyano-2,3 ,4,5-tetrahydro- I H-imidazoi-4-ylmethyl)-3 -((4-fluorophenyl)methyl)-4- (phenylsul fonyl)- I H-I ,4-benzodiazepine; (R)-7-Cyano-4-(N-cyclopropylmethyl-N-propyl)-aminosulfonyl]- I H-imidazol-4- yl)methyl]-3-(phenylmethyl)- I H-I ,4-benzodiazepine; (R)-7-Cyano-4-[(N,N-(dibutylamino))-sulfonyi]- 1 H-imidazol-4-yl)methyl]-3- (phenylmethyl)- 1 H-i ,4-benzodiazepine; o (R)-7-Chloro-4-(methanesulfonyl)-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-3- 00 (phenylmethyl)-1I H-pyrido[3,4-e]- 1,4-diazepine; 1,2,3 ,4-Tetrahydro-7-bromo-4-[(1 H-imidazol-4-yl)methyl]-2-phenylmethyl- 1 (methylsulfonyl)quinoxaline; (R)-7-Cyano-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-3-(phenylmethyl)-4-((imidazol-4- yl)methyisulfonyl)-1I H-i ,4-benzodiazepine; (R)-7-Cyano-2,3,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-3-((2-thienyl)methyl)-4- (propylsulfonyl)- 1 H-i ,4-benzodiazepine; (R)-7-Cyano-2,3 ,4,5-tetrahydro- I H-imidazol-4-ylmethyl)-3 -((2-thienyl)methyl)-4-((2- thienyl)-sulfonyl)- 1 H-i ,4-benzodiazepine; (R)-7-Cyano-2,3 ,4,5-tetrahydro- I H-imidazol-4-ylmethyl)-3 -(phenylmethyl)-4-((3- methylthiopropyi)-sulfonyl)- 1 H-i ,4-benzodiazepine; (R)-7-Cyano-2,3 ,4,5-tetrahydro- I H-imidazol-4-ylmethyl)-3-(phenylmethyl)-4-(((3 methylthioxo)-propyl)-sulfonyl)-1I H-i ,4-benzodiazepine; (R)-7-Cyano-2,3 ,4,5-tetrahydro- I H-imidazol-4-ylmethyl)-3-(phenylmethyl)-4-(((3- methylsulfonyl)-propyl)-sulfonyl)- 1 H-i ,4-benzodiazepine; (R)-7-Cyano-2,3,4,5-tetrahydro- I I H-imidazol-4-ylmethyl)-3-(phenylmethyl)-4-((2- methylpropyl)-sulfonyl)- I H-i ,4-benzodiazepine; (R)-7-Cyano-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-3-(phenylmethyl)-4- (cyclopentylsulfonyl)- 1 H-i ,4-benzodiazepine; (R)-7-Cyano-2,3 ,4,5-tetrahydro- I H-imidazol-4-ylmethyl)-3-(phenylmethyl)-4-((4,4,4- trifluorobutyl)-sulfonyl)- 1 H-i ,4-benzodiazepine; (R)-7-Cyano-2,3,4,5-tetrahydro- 1 H-imidazol-4-yimethyl)-3 -(phenylmethyl)-4- ((phenylmethyl)-sulfonyi)- 1 H-i ,4-benzodiazepine; (R)-7-Cyano-2,3 ,4,5-tetrahydro- I H-imidazol-4-ylmethyl)-3 -(phenylmethyl)-4-[[2-(5-(N- benzoyl)-aminomethyl)-thienyl]-sulfonyl]- 1 H-i ,4-benzodiazepine; (R)-7-Cyano-2,3 ,4,5 -tetrahydro- I H-imidazol-4-ylmethyl)-3-(phenylmethyl)-4-[[2-( 1-(3- chloro-5-methyl-pyridin-2-yl))-pyrrolyl]-sulfonyl]- I H-i ,4-benzodiazepine; (R)-7-Cyano-2,3 ,4,5-tetrahydro- I I H-imidazol-4-ylmethyl)-3 -(phenylmethyl)-4-((4- carboxyphenyl)-sulfonyl)- 1 H-i ,4-benzodiazepine; (R)-7-Cyano-2,3 ,4,5-tetrahydro- 1 I H-imidazol-4-ylmethyl)-3-(phenylmethyl)-4-[((3-methyl- 1 ,2,4-oxadiazol-5-yI)-phenyl)-sulfonyl]- 1 H-i ,4-benzodiazepine; (R)-7-Cyano-2,3 ,4,5 -tetrahydro- 1 H-imidazol-4-ylmethyl)-3-(phenylmethyl)-4-((2,5- dimethoxyphenyl)-sulfonyl)- 1 H-i ,4-benzodiazepine; 0 (R)-7-Cyano-4-[(N-tetrahydroquinolinyl)sulfonyl]- 1 H-imidazol-4-yl)methyl]-3- 00 (phenylmethyl)- 1 H-i ,4-benzodiazepine; (R)-7-Cyano-4-(N,N-bis-[ 1 -(2-methylpropyl)amino]-sulfonyl]- 1 H-imidazol-4-yl)methyl]-3- )phenylmethyl)- 1 H-i ,4-benzodiazepine; (R)-7-Cyano-4-[(N-methyl-N-phenyl)aminosulfonyi]- I H-imidazol-4-yl)methyl]-3- (phenylmethyl)- 1 H-i ,4-benzodiazepine; (R)-7-Cyano-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-3 -(2-(2,6-dimethylphenyl)-ethyl)- C) 10 4-(methylsulfonyl)- 1 H-i ,4-benzodiazepine; (R)-7-Cyano-2,3 ,4,5-tetrahydro- I -(N-phthalimidoethyl)-imidazol-5-ylmethyl)-3- (phenylmethyi)-4-methylsulfonyl)- I H-I ,4-benzodiazepine; (R)-7-Cyano-2,3,4,5-tetrahydro- 1 -[(2-(N,N-dimethylamino)-ethyl)-imidazol-5-ylmethyl]-3- (phenylmethyl)-4-(methylsulfonyl)- 1 H-I ,4-benzodiazepine; (R)-7-Cyano-2,3 ,4,5-tetrahydro- I -[(2-aminoethyl)-imidazol-5-ylmethyl]-3-(phenylmethyl)-4- (methylsulfonyl)- I H-i ,4-benzodiazepine; (R)-7-Bromo-4-(methanesulfonyl)-2,3,4,5-tetrahydro- I H-imidazol-4-ylmethyl)-3 (phenylmethyl)- I H-thieno[2,3-e]- 1 ,4-diazepine; (R)-7-Bromo-4-(methanesulfonyl)-2,3,4,5-tetrahydro- I H-imidazol-4-ylmethyl)-3- (phenylmethyl)- 1 H-thieno[3,2-e]- 1 ,4-diazepine; (R)-4-(methanesulfonyl)-2,3,4,5-tetrahydro- I H-imidazol-4-ylmethyl)-3-(phenylmethyl)- 1 H- 8-oxo-pyrimidino[4,5-e]-I ,4-diazepine; (R)-7-Cyano-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-3-((4-(2-methoxyethoxy)- phenyl)methyl)-4-(phenylsulfonyl)- 1 H-i ,4-benzodiazepine; (R)-7-Cyano-2,3,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-3-((4-(2-(dimethylamino)-ethoxy)- phenyl)methyl)-4-(phenylsulfonyl)- 1 H-i ,4-benzodiazepine; (R)-7-Cyano-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylsulfonyl)-3-(phenylmethyl)-4- (methyisulfonyl)- 1 H-i ,4-benzodiazepine; (R)-7-Cyano-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylsulfonyl)-3-(phenylmethyl)-4- (propylsulfonyl)-1IH-i ,4-benzodiazepine; (R)-7-Cyano-2,3 ,4,5-tetrahydro- I H-imidazol-4-ylsulfonyl)-3-(phenylmethyl)-4- (phenylsulfonyl)-1I H-I ,4-benzodiazepine; (R)-7-Cyano-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylsulfonyl)-3-(Phenylmethyl)-4-(2- thienylsulfonyl)- I H-i ,4-benzodiazepine; 339 7-Cyano-2,3 ,4,5-tetrahydro- 1 H-imidazol-4ylmethyl)-3-(R)-[(R)- 1 -phenyl-ethyl]-4- (methylsulfonyl)- 1 H-i ,4-benzodiazepine; o 7-Cyano-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-3-(R)-[(R)- I -phenyl-ethyl]-4- 00 (propylsulfonyl)- I H-i ,4-benzodiazepine; 7-Cyano-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-yimethyl)-3-(R)-[(R)- 1 -phenyl -ethyl]-4- (phenylsulfonyl)-1I H-I ,4-benzodiazepine; 7-Cyano-2,3 ,4,5-tetrahydro- 1 H-imidazoi-4-yimethyl)-3-(R)-[(R)- I -phenyl -ethyl] thienyl)-suifonyl)- I Hl-i ,4-benzodiazepine; 7-Cyano-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-3-(S)-[(R)- 1 -phenyl-ethyl]-4- C) 10 (methylsulfonyl)- 1 H-I ,4-benzodiazepine; 7-Cyano-2,3 ,4,5-tetrahydro- I H-imidazol-4-ylmethyl)-3-(S)-[(R)- I -phenyl -ethyl] 4- (propysufonyl)- I H-I ,4-benzodiazepine; 7-Cyano-2,3 ,4,5-tetrahydro- 1 I H-imidazol-4-ylmethyl)-3-(S)-[(R)- 1 -phenyli-ethyl] -4- (phenylsulfonyl)- 1 H-i ,4-benzodiazepine; 7-Cyano-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-3-(S)-[(R)- I -phenyl -ethyl] thienyl)-sulfonyl)- I H-i ,4-benzodiazepine; 7-Cyano-2,3 ,4,5-tetrahydro- I H-imidazol-4-ylmethyl)-3-(R)-[(S)- 1 -phenyl -ethyl]-4- (methylsulfonyl)- 1 H-i ,4-benzodiazepine; 7-Cyano-2,3 ,4,5-tetrahydro- 1 H-imidazoi-4-yimethyl)-3-(R)-[(S)- 1 -phenyl -ethyl]-4- (propylsulfonyl)- I H-i ,4-benzodiazepine; 7-Cyano-2,3,4,5-tetrahydro- I H-imidazol-4-ylmethyl)-3-(R)-[(S)- 1 -phenyl-ethyl]-4- (phenylsulfonyl)- I Hl-I ,4-benzodiazepine; 7-Cyano-2,3,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-3-(R)-[(S)- 1 -phenyl -ethyl] thienyl)-sulfonyl)- I Hl-i ,4-benzodiazepine; 7-Cyano-2,3 ,4,5-tetrahydro- I H-imidazol-4-ylmethyi)-3-(S)-[(S)- I -phenylI-ethyl] -4- (methylsulfonyl)- I H-i ,4-benzodiazepine; 7-Cyano-2,3,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-3-(S)-[(S)- 1 -phenyl-ethyl]-4- (propylsulfonyl)- 1 H-i ,4-benzodiazepine; 7-Cyano-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-3-(S)-[(S)- 1 -phenyi-ethyl]-4- (phenylsuifonyl)- I H-i ,4-benzodiazepine; 7-Cyano-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-yimethyl)-3-(S)-[(S)- I -pheny I-ethyl] thienyl)-sulfonyl)- 1 Hl-i ,4-benzodiazepine; 7-Cyano-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-3-(R)-[(R)-phenylcyclopropyl)-4- (methylsulfonyl)- 1 Hl-i ,4-benzodiazepine; 7-Cyano-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-3-(R)-[(R)-phenylcyclopropyl)-4- propylsulfonyl)- 1 H-i ,4-benzodiazepine; o 7-Cyano-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-3-(R)-[(R)-phenylcyclopropyl)-4- 00 phenylsulfonyl)- I H-i ,4-benzodiazepine; 7-Cyano-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-3-(R)-[(R)-phenylcyclopropyl)-4-((2- thienyl)-sulfonyl)- 1 H-I ,4-benzodiazepine; 7-Cyano-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-3-(R)-[(S)-phenylcyclopropyl)-4- (methylsulfonyl)- I H-i ,4-benzodiazepine; 1-10 7-Cyano-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-3-(R)-[(S)-phenylcyclopropyl)-4- propylsulfonyl)- I H-i ,4-benzodiazepine; 7-Cyano-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-yimethyl)-3-(R)-[(S)-phenylcyclopropyl)-4- phenylsulfonyl)- I H-i ,4-benzodiazepine; 7-Cyano-2,3 ,4,5-tetrahydro- 1 I H-imidazol-4-ylmethyi)-3-(R)-[(S)-phenylcyclopropy)-4-((2- thienyl)-sulfonyl)- I H-I ,4-benzodiazepine; 7-Cyano-2,3 ,4,5-tetrahydro- 1 H-imidazoi-4-ylmethyl)-3-(S)-[(R)-phenylcyclopropyl)-4- (methylsulfonyl)- I H-i ,4-benzodiazepine; 7-Cyano-2,3 ,4,5-tetrahydro- I H-imidazoi-4-ylmethyl)-3-(S)-[(R)-phenylcyclopropyl)-4- (propylsulfonyl)- I H-i ,4-benzodiazepine; 7-Cyano-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-3-(S)-[(R)-phenylcyclopropyl)-4- (phenylsulfonyl)- 1 H-i ,4-benzodiazepine; 7-Cyano-2,3 ,4,5-tetrahydro- I H-imidazol-4-yimethyl)-3-(S)-[(R)-phenylcyclopropyl)-4-((2- thienyl)-sulfonyl)- I H-i ,4-benzodiazepine; 7-Cyano-2,3 ,4,5-tetrahydro- 1 H-imidazoi-4-ylmethyl)-3-(S)-[(S)-phenylcyclopropyl)-4- (methylsulfonyl)- I H-i ,4-benzodiazepine; 7-Cyano-2,3 ,4,5-tetrahydro- I H-imidazoi-4-yimethyi)-3-(S)-[(S)-phenylcyclopropyl)-4- (propylsulfonyl)- I H-i ,4-benzodiazepine; 7-Cyano-2,3 ,4,5-tetrahydro- I H-imidazol-4-ylmethyl)-3-(S)-[(S)-phenylcyclopropyl)-4- (phenylsuifonyl)- 1 H-i ,4-benzodiazepine; 7-Cyano-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-3-(S)-[(S)-phenylcyclopropyl)-4-((2- thienyl)-sulfonyl)- 1 H-i ,4-benzodiazepine; (R)-7-Cyano-2,3 ,4,5-tetrahydro- I H-imidazoi-4-ylmethyl)-3 -(phenylmethyl)-4-[(2-(5- (pyridin-2-yl))-thienyl)-sulfonyl])- 1 H-i ,4-benzodiazepine; (R)-7-Cyano-2,3 ,4,5-tetrahydro- I H-imidazol-4-ylmethyl)-3 -(phenylmethyl)-4- 1,2- isoxazol-3-yI))-thienyl)-sulfonyl])- I H-I ,4-benzodiazepine; (R)-7-Cyano-2,3 ,4,5-tetrahydro- 1 H-imidazol-2-yI)-propyl)-3-(phenylmethyl)-4- __(phenylsulfonyl)- 1 H-I ,4-benzodiazepine; o (R)-7-Cyano-2,3 ,4,5-tetrahydro- 1 1 H-imidazol-2-yl)-propyl)-3 -(phenylmethyi)-4- 00 (methylsulfonyl)- 1 H-I ,4-benzodiazepine; (R)-7-Cyano-2,3 ,4,5-tetrahydro- I H-imidazol-2-y1)-propyi)-3-(phenylmethyl)-4- (propylsulfonyl)- 1 H-I ,4-benzodiazepine; (R)-7-Cyano-2,3 ,4,5-tetrahydro- 1 H-imidazol-2-yI)-propyl)-3-(phenylmethyl)-4-((2- thienyl)-sulfonyl)- 1 H-i ,4-benzodiazepine; (R)-7-Cyano-2,3,4,5-tetrahydro- 1 1 H-imidazol-2-yI)-ethylsulfonyl)-3 -(phenylmethyl)-4- C) 10 (phenylsulfonyl)- 1 H-i ,4-benzodiazepine; (R)-7-Cyano-2,3 ,4,5-tetrahydro- I H-imidazol-2-yl)-ethylsulfonyl)-3-(phenylmethyl-4- (methylsulfonyl)- 1 H-I ,4-benzodiazepine; (R)-7-Cyano-2,3 ,4,5-tetrahydro- 1 1 H-imidazol-2-yl)-ethylsulfonyl)-3 -(phenylmethyl)-4- (propylsulfonyl)- 1 H-i ,4-benzodiazepine; (R)-7-Cyano-2,3,4,5-tetrahydro- I I H-imidazol-2-yl)ethylsulfonyl)-3-(phenylmethyl)-4-((2- thienyl)-sulfonyl)-1I H-I ,4-benzodiazepine; (R)-7-Cyano-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-3-(phenylmethyl)-4-(( 1 -oxoethyl)- amino)- 1 H-I ,4-benzodiazepine; (R)-7-Cyano-2,3 ,4,5 -tetrahydro- 1 H-imidazol-4-ylmethyl)-3 -(phenylmethyl)-4- Z0 (methanesulfonyl amino)- 1 H-i ,4-benzodiazepine; and (R)-7-Cyano-2,3 ,4,5-tetrahydro- 1 I H-imidazol-4-ylmethyl)-3-(phenylmethyl)-4- (phenylsulfonylamino)- 1 H-i ,4-benzodiazepine.
109. 141. A method of treating a synucleinopathic subject, the method comprising, administering to a synucleinopathic subject a farnesyl transferase inhibitor compound of the formula: ID 0 R 3 O 00 R 2 N NO S---(CH2)n (N N 0 R4 or a stereoisomeric form, or a pharmaceutically acceptable acid or base addition salt form thereof, in a therapeutically effective amount, wherein RI is Cl, Br, CN, optionally substituted phenyl, or optionally substituted or 4-pyridyl; R 2 is optionally substituted lower alkyl, or optionally substituted aralkyl; R 3 and Rs are each independently optionally substituted lower alkyl, optionally substituted aryl, or optionally substituted heterocyclo; R4 is hydrogen or lower alkyl; ZI is CO, SO 2 CO 2 or SO2 N(R 5 and n is 1 or 2.
110. 142. The method according toclaim 141, wherein Ri is Br, or CN; R 2 is optionally substituted benzyl; R 3 is optionally substituted lower alkyl, optionally substituted phenyl, optionally substituted 2-thienyl, or optionally substituted 1-piperidinyl; R4 is hydrogen, or methyl; ZI is CO, SO2, or SO 2 R 5 is optionally substituted lower alkyl or optionally substituted phenyl; and n is 1.
111. 143. The method according to claim 141, wherein Ri is CN; R 2 is optionally substituted benzyl; R 3 is optionally substituted lower alkyl, optionally substituted phenyl, optionally substituted C) 00 R 4 is hydrogen, or methyl; Z is CO, or S0 2 ;and n isi1.
112. 144. The method according to claim 14 1, wherein IND R, is CN; (f 10 R 2 is benzyl; R 3 is n-propyl, n-butyl, 3-methoxypropyl, 2-thienyl, 5-bromo-2-thienyl, phenyl, 4- methoxyphenyl, or I1-piperidinyl; R 4 is hydrogen; Z is S0 2 and n isi1.
113. 145. The method according to claim 141, wherein the compound is selected from the group consisting of: (R)-2,3,4,5-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-3-(phenylmethyl)-4-(2-thienylsulfonyl)- 1H- 0 I ,4-benzodiazepine-7-carbonitrile; (R)-7-cyano-2,3 ,4,5-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-4-( 1-oxobutyl)-3 -(phenylmethyl)- I Hl-i ,4-benzodiazepine; (R)-4-[(5-bromo-2-thienyl)sulfonyl]-7-cyano-2,3,4,5-tetrahydro- 1 H-imidazol-4-yl methyl)- 3-(phenyl methyl)- 1 H-i ,4-benzodiazepine; (R)-7-cyano-2,3 ,4,5-tetrahydro-l1-(1 H-imidazol-4-yl methyl)-4-[(4-methoxyphenyl)sulfonyl]-3- (phenylmethyl)- 1 H-i ,4-benzodiazepine; (R)-7-cyano-2,3 ,4,5-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-3-(phenyl methyl)-4- (phenylsulfonyl)- 1 H-i ,4-benzodiazepine; (R)-7-cyano-2,3 ,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-3-(phenylmethyl)-4- (propylsulfonyl)-1 H-I ,4-benzodiazepine; (R)-4-(butylsulfonyl)-7-cyano-2,3,4,5-tetrahydro-1I-(I H-imidazol-4-ylmethyl)-3- (phenylmethyl)- I H-i ,4-benzodiazepine; (R)-7-cyano-2,3,4,5-tetrahydro- 1 H-imidazol-4-ylmethyl)-3-(phenylmethyl)-4-( I piperidinylsulfonyl)- 1 Hl-I ,4-benzodiazepine; I ID (R)-4-(3-methoxypropylsulfonyl)-7-cyano-2,3,4,5-tetrahydro- 1-(1H-imidazol-4-ylmethyl)-3- S (phenylmethyl)- 1 H-1,4-benzodiazepine; and O pharmaceutically acceptable salts thereof. 00
114. 146. The method according to claim 141, wherein the pharmaceutically acceptable salt is selected from the group consisting of the hydrochloride salt, the methanesulfonic acid O salt and the trifluoroacetic acid salt. (c Is 147. The method according to claim 141, wherein the compound is tetrahydro-1 H-imidazol-4-ylmethyl)-3-(phenylmethyl)-4-(2-thienylsulfonyl)-1 H-1,4- benzodiazepine-7-carbonitrile.
115. 148. A method of treating a synucleinopathic subject, the method comprising, administering to a synucleinopathic subject a farnesyl transferase inhibitor compound of the formula: R 7 R 8 B A- R 3 R 4 R 5 R 6 R 9 R 10 R 7 I R 8 B~\C D AI 00 N RrSs-Tt-Z N (Ni R 9 R 10 or a stereoisomeric form, or a pharmaceutically acceptable acid or base addition salt form thereof, in a therapeutically effective amount, wherein 1, m, r, s and t are 0 or 1; n isO0, 1 or 2; Y is selected from the group consisting of CHR' 2 SO 2 SO 3 CO, C0 2 0, NR" 3 S0 2 NR' 4 61 2719 2 22 CONR' 5 C(NCN), C(NCN)NR NR" CO, NR" 8 SO 2 CONR9 NR SO 2 NR NR S(O)(NR 2 S(NR 2)(NR 25 or without Y; Z is selected from the group consisting of CR' 2 S, SO, S02, SO 3 CO, C0 2 0, NR' 3 SO 2 NR', CONR' 5 NR 26 NR 27 0NR 2 8 NR 2 0, NR 3 S02 NR 31 NR 2 SO 2 NR 3 C(NCN), NR" C(NCN)NR 3 NR" CO, NR 31CONR NR 39C0 2 OCONR 4 0 S(O)(NR 41 S(NR 42)(NR 4) or CHR 12; or without Z; R 7 R 8are selected from the group consisting of hydrogen, halo, nitro, cyano and U-R4; U is selected from the group consisting of S, 0, NR 45 CO, SO, S02, C0 2 NR 4 1 C0 2 NR 47 CONR NR 4 SO 2 NR" 0 S02 NR" 1 S02 NR 52 NR 5 CO, CONR 54 P0 2 R" 5 and P0 3 R" 6 or without U; R 9 R' 0 R1 2 R1 3 R 14 1 5 R1 6 1 7 R1 8 R 9 R 2 0 R 2 1 R R 23 R 24 R 2 5 R 26 R 27 R 28 R 29 R 30 ,R 3 1 R 32 R 33 R 34 R 35 R 36 R 37 R 38 ,R 39 ,R 40 ,R 4 1 R 42 R 43 R 45 R 46 R 47 R 48 R 49 R 50 R51, R 52, R 53 R 54 R 5 5, R 56 R 57, R 58 and R 5 9 are selected from the group consisting of hydrogen, lower alkyl, aryl, heterocyclo, substituted alkyl or aryl or substituted hetercyclo; ID R" and R 44 are selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, aralkyl, cycloalkyl, aryl, O substituted aryl, heterocyclo, substituted heterocyclo; 00 R 2 R 3 R 4 R 5 and R 6 are selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, aralkyl, cycloalkyl, aryl, substituted aryl, heterocyclo, substituted heterocyclo, cyano, carboxy, carbamyl CONH 2 substituted carbamyl (where nitrogen may be substituted by groups selected from hydrogen, alkyl, substituted alkyl, aryl or aralkyl, substituted aryl, heterocyclo, substituted heterocyclo), alkoxycarbonyl; any two of R 2 R 3 R 4 R 5 and R 6 0 10 can join to form a cycloalkyl group; any two of R, R 2 R 3 R 4 R 5 and R 6 together can be oxo, except when the carbon atom bearing the substituent is part of a double bond; R, S and T are selected from the group consisting of CH 2 CO and CH(CH 2 )p Q wherein Q is NR 5 7 R 58 OR 59 or CN; and p is 0, 1 or 2; A, B and C are carbon, oxygen, sulfur or nitrogen; D is carbon, oxygen, sulfur or nitrogen or without D; and with the provisos: 1. When I and m are both 0, n is not 0; 2. R" may be hydrogen except when Z is SO, or when Z is O, NR' 3 or S and the carbon to which it is attached is part of a double bond or when Y is SO 2 C0 2 NR' 8 SO 2 S(O)(NR23), or S(NR24)(NR25); 3. R 44 may be hydrogen except when U is SO, SO 2 NR 46 CO 2 or NR 49 SO 2
116. 149. The method of claim 148, wherein the compound has the formula: R 8 7 ,R O A 00 Z R 1 N- n SRrS TtY R 1 R 2 R 3 R 4 R, R 6 O N (N R 9 R 10 wherein r, s and t are 0 or 1; 1 is 0; m is 1; n is 1; Y is selected from the group consisting of CHR 2 SO 2 SO3, CO 2 O, NR' 1 SO2 NR 1 4 CONR is C(NCN), C(NCN)NR 1 6 NR 1 7 CO, NR' 8 SO2, CONR 9 NR 2 0 SO 2 NR 21 NR 22 S(O)(NR 23 S(NR 24 )(NR 25 or without Y; Z is selected from the group consisting of S, SO, SO2, SO3, CO, CO 2 O, NR 1 3 SO2 NR 1 4 CONR' 5 NR 26 NR 27 ONR 28 NR 29 0, NR 30 S02 NR 31 NR 32 S02, NR 33 C(NCN), NR 34 C(NCN)NR 3 NR 36 CO, NR 37 CONR 3 8 NR 39 CO 2 OCONR 40 S(O)(NR41), or S(NR42)(NR43); R 7 R 8 are selected from the group consisting of hydrogen, halo, nitro, cyano and U-R 44 U is selected from the group consisting of S, O, NR 45 CO, SO, SO 2 CO 2 NR 46 CO 2 NR 47 CONR 48 NR 49 SO2, NR 50 S02 NR 5 SO2 NR 52 NR 53 CO, CONR 54 PO 2 R 55 and PO3 R 56 or without U; R 9 R, R I 2 R 1 R 1 R 1 R R9, R2, R 2 R2 R 2 R 2 4, R 25 R 27 R 2 8 R 29 R 3 R, R 3 2 R 3 3 R 3 R 3 4 R, 36 ,R 37 R 38 R 39 R 40 R 4 1 R 42 R 43 R 45 R 46 R 47 R 48 R 49 R 5 0 R 51 R 52 R 53 R 5 4 R 55 R 56 R 57 R 58 and R 5 9 are selected from the group consisting of hydrogen, lower alkyl, aryl, heterocyclo, substituted alkyl or aryl; R 1 and R 4 4 are selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, aralkyl, cycloalkyl, aryl, substituted aryl, heterocyclo, substituted heterocyclo; ID SR', R 2 R R 4 R 5 and R 6 are selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, aralkyl, O cycloalkyl, aryl, substituted aryl, heterocyclo, substituted heterocyclo, cyano, 00 alkoxycarbonyl, carboxy, carbamyl, substituted carbamyl wherein substituents on the nitrogen of the substituted carbamyl are selected hydrogen, alkyl, substituted alkyl, aryl or aralkyl, substituted aryl, heterocyclo, substituted heterocyclo; any two of R 2 R 3 R 4 R N and R 6 can join to form a cycloalkyl group; any two of R 1 R 2 R 3 R 4 R 5 and R 6 together c can be oxo, except when the carbon atom bearing the substituent is part of a double bond; I\ R, S and T are selected from the group consisting of CH 2 and CH(CH 2 )p Q wherein Q is NR 57 R 5 8 OR 59 or CN; wherein p is 0, 1 or 2; and A, B, C and D are carbon; its enantiomers, diastereomers, pharmaceutically acceptable salts and solvates thereof; with the provisos that: 1. R" may be hydrogen except when Z is SO, or when Z is O, NR 1 3 or S and the carbon to which it is attached is part of a double bond or when Y is SO 2 CO2, NR 1 8 SO 2 S(O)(NR 23 or S(NR 24 )(NR 2 5 and 2. R 44 may be hydrogen except when U is SO, SO 2 NR 46 CO 2 or NR 49 SO 2
117. 150. The method ofclaim 149, wherein 1, m, r, s and t are 0 or 1; n is 1 or 2; Y is CHR 1 2 SO 2 SO 3 CO2, SO 2 NR 1 4 CONR 1 5 or without Y; Z is SO2, SO 3 CO, CO2, NR 1 3 SO 2 NR' 4 CONR" S NR 3 0 SO 2 NR 31 NR 32 SO 2 NR 36 CO, NR 37 CONR 3 8 or NR 39 CO 2
118. 151. The method of claim 150, wherein 1, r, s, and t is 0; Y is CHR 1 2 SO 2 SO 2 NR 1 4 or CONR' 5 or without Y; and Z is SO 2 SO 3 CO, C0 2 SO 2 NR 1 4 CONR' 1 NR 3 0 SO 2 NR 3 1 NR 32 SO 2 NR 36 CO, NR 37 or CONR 38 NR 39 CO 2
119. 152. The method of claim 148, wherein R 7 R 8 is halogen, nitro, cyano or U-R 44 wherein U is S, O, NR 46 CO 2 NR 47 CONR 48 R 44 is hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, 349 aralkyl, cycloalkyl, aryl, substituted aryl, heterocyclo or substituted heterocyclo, R 46 and R 47 is hydrogen, lower alkyl, aryl substituted alkyl or aryl. C.) 00 153. The method of claim 148, wherein the salt is of an organic or inorganic acid.
120. 154. The method of claim 153, wherein the salt is of hydrogen chloride, hydrogen bromide, methanesulfonic acid, hydroxyethanesulfonic acid, sulfuric acid, acetic acid, trifluoroacetic acid, maleic acid, benzenesulfonic acid, toluenesulfonic acid, nitric acid, IND phosphoric acid, boric acid, tartaric acid, citric acid, succinic acid, benzoic acid, ascorbic acid C) 10 or salicyclic acid.
121. 155. The method of claim 148, wherein the compound is: N-[6-bromo- 1,2,3 ,4-tetrahydro- 1 H-imidazol-4-ylmethyl)-3-quinolinyl]- 1 naphthalenesulfonamide, dihydrochloride; N-[6-bromo- 1,2,3 ,4-tetrahydro-lI-(1 H-imidazol-4-ylmethyl)-3-quinolinyl]- 1- naphthalenecarboxamide, dihydrochioride; N-[6-bromo- 1,2,3 ,4-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-3-quinolinyl]-N- (phenylmethyl)methanesulfonamide, di hydrochloride; N-[6-bromo- 1,2,3 ,4-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-3-quinolinyl]benzenesulfonamide, dihydrochloride; N-[6-bromo- 1,2,3 ,4-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-3-quinolinyl]-N- (phenylmethyl)acetamide, dihydrochloride; N-[6-bromo- 1,2,3 ,4-tetrahydro- 1-(1 H-imidazol-4-ylmethyl)-3-quinolinyl]-N-(4- methoxyphenyl)methyl] methanesulfonamide, monohydrochloride; N-[6-bromo- 1,2,3 ,4-tetrahydro-lI-(1 H-imidazol-4-ylmethyl)-3 -quinolinyl]-N- methylphenyl)methyl]methanesulfonamide monohydrochioride; N-[6-cyano- 1,2,3 ,4-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-3-quinolinyl]-N-[(3- methylphenyl)methyllbenzenesul fonamide monohydrochioride; N-[6-cyano- 1,2,3 ,4-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-3-quinolinyl]-N-[(2- methylphenyl)methyl]benzenesulfonamide monohydrochioride; N-[6-cyano- 1,2,3 ,4-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-3 -quinolinyl]-N- (phenylethyl)benzenesul fonamide monohydrochloride; N-[6-Cyano- 1,2,3 ,4-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-3 -quinolinyl]-N-[(2- ethoxyphenyl)methyl]benzenesulfonamide monohydrochloride; N-[6-Cyano- 1 ,2,3,4-tetrahydro- 1 H-imidazol-4-ylmethyl)-3-quinolinyl]-N- __(phenylmethyl)benzenesulfonamide monohydrochioride; o N-[6-Cyano- 1,2,3,4-tetrahydro- 1 H-imidazol-4-ylmethyl)-3-quinolinyl]-N-[(2,3- 00 dimethoxyphenyl)methyl] benzenesulfonamide monohydrochloride; N-[6-Cyano- 1,2,3,4-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-3-quinolinyl]-N-[(3 dimethylphenyl)methyl]benzenesulfonamide monohydrochioride; N-[6-Cyano- 1,2,3,4-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-3-quinolinyl]-N-[( 1- naphthalenyl)methyl] benzenesulfonamide monohydrochioride; N-[6-Cyano- 1,2,3,4-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-3-quinolinyl]-N-[(2- thiophene)methyl]benzenesulfonamide monohydrochioride; N-[6-Cyano- 1,2,3 ,4-tetrahydro- 1 H-imidazol-4-ylmethyl)-3-quinoliriyl]-N-[(2,5- dimethylphenyl)methyl]benzenesulfonamide monohydrochioride; N-[6-Cyano- 1,2,3 ,4-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-3-quinolinyl]-N-[(3- thiophene)methyll benzenesulfonamide monohydrochioride; N-[6-Cyano- 1,2,3 ,4-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-3-quinolinyl]-N- chilorophenyl)methyl] benzenesul fonamide monohydrochioride; N-[6-Cyano- 1,2,3 ,4-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-3-quinolinyl]-N-[(2- fluorophenyl)methyl] benzenesulfonamide monohydrochioride; N-[6-Cyano- 1,2,3 ,4-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-3-quinoliriyl]-N-[(3- pyridyl)methyl]benzenesulfonamide monohydrochioride; N-[6-Cyano- 1,2,3 ,4-tetrahydro-l1-[[1 -(methyl)- 1H-imidazol-5-yllmethyl]-3-quinolinyl]-N- (phenylmethyl)benzenesul fonamide monohydrochioride; N-[6-Cyano- 1,2,3 ,4-tetrahydro-l1-[[1 -(methyl)- IH-imidazol-5-yl]methyl]-3-quinolinyl]-N-[(3- thiophenemethyl] benzenesulfonamide monohydrochioride; N-[6-Cyano- 1,2,3 ,4-tetrahydro- 1 H-imidazol-4-ylmethyl)-3-quinolinyl]-N- (phenylmethyl)methanesulfonamide monohydrochioride; N-[6-Cyano- 1,2,3 ,4-tetrahydro- 1 -(methyl)- I H-imidazol-5-yllmethyl]-3-quinolinyl]-N- (phenylmethyl)methanesulfonamide monohydrochioride; (R)-N-[6-Cyano- 1,2,3 ,4-tetrahydro- 1 -(methyl)- 1H-imidazol-5-yI]methyl]-3-quinolinyl]-N- (phenylmethyl)benzenesulfonamide monohydrochioride.
122. 156. A method of treating a synucleinopathic subject, the method comprising, administering to a synucleinopathic subject a farnesyl transferase inhibitor compound of the formula: R 8 7 ,R B\ D 00 N-1 Rr~s~tYR 1 R 2 R 4 R 6 N R 9 R 10 or a stereoisomeric form, or a pharmaceutically acceptable acid or base addition salt form thereof, in a therapeutically effective amount, wherein Yis selected from the group consisting of CHR' 2 SO 2 SO 3 GO, Go 2 0, NR' 3 SO 2 NR 4 16 1719 20 21 22 CONR' 5 C(NCN), C(NCN)NR", NR" CO, NR" SO 2 CONR9 NR SO 2 NR 'NR S(O)(NR 2 1 3 and S(NR 24 )(NR" 5 or without Y; Z is selected from the group consisting of S, S0, So 2 SO 3 GO, C0 2 0, NR 3 SO 2 NR' 4 CONR' 5 NR 26 NR 2 1, 0NR 2 1, NR 29 0, NR 3 1 SO 2 NR 3 NR 32 SO 2 NR 33 C(NCN), NR 34 N 36 O NR 3 1 CONR 3 NR 39 CO2, OCONR",S 0 N and C(NCN)(NR R G, R 7 and R 8 are selected from the group consisting of hydrogen, halo, nitro, cyano and U--R 44 U is selected from the group consisting of 5, 0, NR 45 GO, SO, SO 2 CO 2 NR 4 CO 2 NR 4 CONR NR S02, NR" SO 2 NR" 1 SO 2 NR 52 NR 3 GO, GONR 5 4 P0 2 R" 5 and P0 3 R" or without U; 9 10 131I5 1 17 18 19 20 21 22 23 24 25 26 27 28 9 R9,R10 ,R 2 R 3 R 4 R 5 R 6 ,R R R R ,R R R R R ,R ,R R, R 29 51 52 53 54 55 56 59 5 RR ,R ,RRRR R R 57 R 8 and R9 are selected from the group consisting of hydrogen, lower alkyl, aryl, heterocyclo, substituted alkyl and aryl; R I and R 44 are selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, aralkyl, cycloalkyl, aryl, substituted aryl, heterocyclo, and substituted heterocyclo; ID R, R R 4 R and R 6 are selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, aralkyl, ¢O cycloalkyl, aryl, substituted aryl, heterocyclo, substituted heterocyclo, cyano, 00 alkoxycarbonyl, carboxy, carbamyl, and substituted carbamyl wherein substituents on the nitrogen of the substituted carbamyl are selected from the group consisting of hydrogen, alkyl, substituted alkyl, aryl, aralkyl, substituted aryl, heterocyclo, and substituted \Oheterocyclo; any two of R 2 R 3 R 4 R 5 and R 6 can join to form a cycloalkyl group; any two of R 2 R 3 R 4 R 5 and R 6 together can be oxo, except when the carbon atom bearing I\ the substituent is part of a double bond; R, S and T are selected from the group consisting of CH 2 and CH(CH 2 )p Q wherein Q is NR 57 R 5 8 OR 59 or CN; p is 0, 1 or 2; and A, B, C and D are carbon; its enantiomer, diastereomer, pharmaceutically acceptable salt or solvate thereof; with the provisos that: 1. R" 1 may be hydrogen except when Z is SO, or when Z is O, NR 1 3 or S and the carbon to which it is attached is part of a double bond or when Y is SO 2 CO 2 NR 1 8 SO2, S(O)(NR 2 or S(NR 24 )(NR 25 and 2. R 44 may be hydrogen except when U is SO, SO2, NR 46 CO 2 or NR 49 SO2.
123. 157. The method of claim 156, wherein r, s and t are 0 or 1; Y is CHR 1 2 SO2, SO3, CO, CO2, SO2 NR 1 4 CONR' 1 or without Y; Z is CR 1 2 SO 2 SO3, CO, CO 2 NR 1 3 SO 2 NR 4 CONR 15 NR 30 SO 2 NR 31 NR 32 SO2, NR 36 CO, NR 3 7 CONR 38 NR 39 CO 2 or without Z.
124. 158. The method of claim 156, wherein r, sand tare 0 or 1; Y is CHR 1 2 SO 2 SO3, CO, CO 2 SO 2 NR 1 4 CONR' 5 or without Y; Z is CR12, SO 2 SO 3 CO, CO 2 NR 1 3 SO 2 NR 1 4 CONR" 5 NR 3 0 SO 2 NR 31 NR 32 SO 2 NR 36 CO, NR 37 CONR 38 NR 39 CO 2 or without Z.
125. 159. The method of claim 156, wherein r, s, and t is 0; Y is CHR 1 2 SO 2 CO, SO 2 NR' 4 or CONR 1 5 or without Y; and Z is CR 1 2 SO 2 SO 3 CO, CO 2 SO 2 NR' 4 CONR' 1 NR 30 SO 2 NR 31 NR 32 SO 2 NR 36 CO, NR 37 CONR 38 NR 39 CO 2 or without Z.
126. 160. The method of claim 156, wherein R 7 R 8 is halogen, nitro, cyano or -R4 wherein U is S, 0, NR 4 6 C0 2 NR 4 1 CONR 4 8 R 44 is hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, aralkyl, cycloalkyl, aryl, substituted aryl, 00 heterocyclo or substituted heterocyclo, R 4 6 and R 47 is hydrogen, lower alkyl, aryl substituted alkyl or aryl. r- 161. The method of claim 156, wherein the compound is selected from the group consisting of: IND N-[6-bromo- 1 ,2,3,4-tetrahydro- 1 H-imidazol-4-ylmethyl)-3-quinolinyl]- I1- naphthalenesulfonamide, dihydrochloride; N-[6-bromo- 1,2,3,4-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-3-quinolinyl]- 1- naphthalenecarboxamide, d ihydrochloride; N-[6-bromo- 1,2,3 ,4-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-3-quinolinyl]-N- (phenylmethyl)methanesul fonamide, dihydrochioride; N-[6-bromo- 1,2,3 ,4-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-3-quinolinyl]benzenesulfonamide, dihydrochloride; N-[6-bromo- 1,2,3 ,4-tetrahydro- 1-(1 H-imidazol-4-ylmethyl)-3-quinolinyl]-N- (phenylmethyl)acetamide, dihydrochloride; N-[6-bromo- 1,2,3 ,4-tetrahydro- 1 H-imidazol-4-ylmethyl)-3-quinolinyl]-N-(4- methoxyphenyl)methyl] methanesulfonamide, monohydrochioride; N-[6-bromo- 1,2,3 ,4-tetrahydro- 1-(1 H-imidazol-4-ylmethyl)-3-quinolinyl]-N-[(4- methylphenyl)methyl] methanesulfonamide monohydrochloride; N-[6-cyano- 1,2,3 ,4-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-3-quinolinyl]-N-[(3- methylphenyl)methyl] benzenesulfonamide monohydrochloride; N-[6-cyano- 1,2,3,4-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-3-quinolinyl]-N-[(2- methylphenyl)methyl] benzenesulfonamide monohydrochioride; N-[6-cyano- 1,2,3 ,4-tetrahydro- 1 H-imidazol-4-ylmethyl)-3-quinolinyl]-N- (phenylethyl)benzenesulfonamide monohydrochloride; N-[6-Cyano- 1,2,3 ,4-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-3-quinolinyl]-N-[(2- ethoxyphenyl)methyl] benzenesulfonamide monohydrochioride; N-[6-Cyano- 1,2,3 ,4-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-3-quinolinyl]-N- (phenylmethyl)benzenesulfonamide monohydrochloride; N-[6-Cyario- 1,2,3 ,4-tetrahydro- 1 H-imidazol-4-ylmethyl)-3-quinolinyl]-N-[(2,3- dimethoxyphenyl)methyl] benzenesul fonamide monohydrochloride; N-[6-Cyano- 1,2,3 ,4-tetrahydro- 1 H-imidazol-4-ylmethyl)-3-quinolinyl]-N-[(3 dimethylphenyl)methyl] benzenesulfonamide monohydrochioride; o N-[6-Cyano- 1,2,3 ,4-tetrahydro- 1 H-imidazol-4-ylmethyl)-3-quinolinyl]-N-[( 1- 00 naphthalenyl)methyl]benzenesul fonamide monohydrochioride; N-[6-Cyano- 1,2,3 ,4-tetrahydro- 1 H-imidazol-4-ylmethyl)-3-quinolinyl]-N-[(2- thiophene)methyl] benzenesulfonamide monohydrochioride; N-[6-Cyano- 1,2,3 ,4-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-3-quinolinyl]-N-[(2,5- dimethylphenyl)methyljbenzenesulfonamide monohydrochioride; N-[6-Cyano- 1,2,3 ,4-tetrahydro- 1 H-imidazol-4-ylmethyl)-3-quinolinyl]-N-[(3- C) 10 thiophene)methyl] benzenesulfonamide monohydrochioride; N-[6-Cyano- 1,2,3 ,4-tetrahydro-l1-(1 H-imidazol-4-ylmethyl)-3-quinolinyl]-N-[(3- chlorophenyl)methyl]benzenesulfonamide monohydrochioride; N-[6-Cyano- 1,2,3 ,4-tetrahydro-lI-(1 H-imidazol-4-ylmethyl)-3-quinolinyl]-N-[(2- fluorophenyl)methyl]benzenesulfonamide monohydrochioride; N-[6-Cyano- 1,2,3 ,4-tetrahydro- 1 H-imidazol-4-ylmethyl)-3-quinolinyl]-N-[(3- pyridyl)methyl]benzenesulfonamide monohydrochioride; N-[6-Cyano- 1,2,3 ,4-tetrahydro-l1-[[1 -(methyl)- 1H-imidazol-5-yl]methyll-3 -quinolinyl]-N- (phenylmethyl)benzenesulfonamide monohydrochioride; N-[6-Cyano- 1,2,3 ,4-tetrahydro-l1-[[1 -(methyl)- IH-imidazol-5-yl]methyl]-3-quinolinyl]-N-[(3- thiophenemethyl]benzenesulfonamide monohydrochioride; N-[6-Cyano- 1,2,3 ,4-tetrahydro- 1 H-imidazol-4-ylmethyl)-3-quinolinyl]-N- (phenylmethyl)methanesulfonamide monohydrochioride; N-[6-Cyano- 1,2,3 ,4-tetrahydro-l1-[[1 -(methyl)- 1 H-imidazol-5-yl]methyl]-3-quinol inyl]-N- (phenylmethyl)methanesulfonamide monohydrochioride; (R)-N-[6-Cyano-1I,2,3,4-tetrahydro- 1 -(methyl)- 1H-imidazol-5-yljmethyl]-3-quinolinyl]-N- (phenylmethyl)benzenesulfonamide monohydrochloride.
127. 162. A method of treating a synucleinopathic subject, the method comprising, administering to a synucleinopathic subject a famnesyl transferase inhibitor compound of the formnula: SoS NC N N O o N- or a stereoisomeric form, or a pharmaceutically acceptable acid or base addition salt form thereof, in a therapeutically effective amount.
128. 163. The method of any of claims 130-162, wherein the synucleinopathic subject has a synucleinopathy selected from the group consisting of: Parkinson's disease, diffuse Lewy body disease, and multiple system atrophy disorder.
129. 164. The method of claim 163, wherein the subject is a human.
130. 165. The method of claim 164, wherein the effective amount comprises about of body weight to about 1000mg/kg of body weight at a frequency of administration from once a day to once a month.
131. 166. The method of claim 165, further comprising administering to the subject an amount of one or more non-famesyl transferase inhibitor compounds effective to treat a neurological disorder.
132. 167. The method of claim 164, wherein each non-farnesyl transferase inhibitor compound is selected from the group consisting of: dopamine agonist, DOPA decarboxylase inhibitor, dopamine precursor, monoamine oxidase blocker, cathechol 0-methyl transferase inhibitor, anticholinergic, and NMDA antagonist. ID S168. The method of claim 166, wherein each non-famesyl trasferase inhibitor S compound is selected from the group consisting of Memantine, Aricept, and other Sacetylcholinesterase inhibitors. OO 00
133. 169. An article of manufacture comprising packaging material and a farnesyl transferase inhibitor compound of any of claims 130-162, wherein the article of manufacture further comprises a label or package insert indicating that the farnesyl transferase inhibitor compound can be administered to a subject for treating a synucleinopathy. (N 0 10 170. The article of manufacture of claim 169, wherein the synucleinopathy is selected from the group consisting of: Parkinson's disease, diffuse Lewy body disease, and multiple system atrophy disorder.
134. 171. The article of manufacture of claim 169, further comprising one or more non- farnesyl transferase inhibitor compounds effective to treat a neurological disorder.
135. 172. The article of manufacture of claim 169, wherein each non-farnesyl transferase inhibitor compound is selected from the group consisting of: dopamine agonist, DOPA decarboxylase inhibitor, dopamine precursor, monoamine oxidase blocker, cathechol 0-methyl ?0 transferase inhibitor, anticholinergic, and NMDA antagonist.
136. 173. A method of treating a synucleinopathic subject, the method comprising, administering to a synucleinopathic subject a farnesyl transferase inhibitor compound of the formula: 357 O A B II R O R J R7a N 18 R 8 or a stereoisomeric form, or a pharmaceutically acceptable acid or base addition salt form thereof, in a therapeutically effective amount, wherein: one of a, b, c and d represents N or N+O and the remaining a, b, c, and d groups represent carbon, wherein each carbon has an R' or R 2 group bound to said carbon; or each of a, b, c, and d is carbon, wherein each carbon has an R' or R 2 group bound to said carbon; the dotted line represents optional bonds; X represents N or CH when the optional bond to C11 is absent, and represents C when the optional bond to C11 is present; when the optional bond is present between carbon atom 5 and carbon atom 6 then there is only one A substituent bound to C-5 and there is only one B substituent bound to C-6 and A or B is other than H; when the optional bond is not present between carbon atom 5 and carbon atom 6 then there are two A substituents bound to C-5, wherein each A substituent is independently selected, and two B substituents bound to C-6, wherein each B substituent is independently selected, and wherein at least one of the two A substituents or one of the two B substituents are H, and wherein at least one of the two A substituents or one of the two B substituents is other than H; A and B are independently selected from the group consisting of: H; -R 9 R 9 -C(O)-R 9 -R9-CO2-R 9 a; -(CH 2 )pR 26 -C(O)N(R 9 2 wherein each R 9 is the same or different; -C(O)NHR 9 -C(O)NH-CH 2 -C(O)-NH 2 C(O)NHR; (10) {-CH,)C(R)ORa; (11) -(CH 2 2 wherein each R 9 is the same or different; (12) -CH 2 )pC(O)R 9 (13) (CH 2 )pC(O)R 2 (14) -(CH 2 )pC(O)N(R 9 2 wherein each R9 is the same or different; (15) -(CH 2 )pC(O)NH(R 9 (16) (CH 2 )pC(O)N(R 26 2 00 wherein each R 26 is the same or different; (17) -~(CH 2 )pN(R 9 9 a; (18) (CH 2 )pN(R 26 2 wherein R 26is the same or different; (19) (CH 2 )pNHC(O)R 5 (20) (CH 2 )pNHC(O) 2 R 5 1; (21) (CH 2 )pN(C(O)R 27 ,a) 2 wherein each R 27 a is the same or different; (22) -(CH 2 )pNR 1 C(O)R 27 (23) -(CH 2 )pNR 1 C(O)R 27 wherein R 5 1 is not H, and R 5 1 and R 27 taken together with the atoms to which they are bound form a 5 or 6 membered heterocycloalkyl ring consisting; (24)- (CH 2 )pNR 5 C(O)NR 27 (25) -(CH 2 )pNR 5 C(O)NR 2 1 wherein R 5 1 is not H, and and R 27 810 taken together with the atoms to which they are bound form a 5 or 6 membered (i heterocycloalkyl ring; (26) (CH 2 )pNR 5 C(O)N(R 27 a 2 wherein each R 27 a is the same or different; (27) -CH 2 )pNHSO 2 N(R 5 wherein each R 5 1 is the same or different; (28) (CH 2 )pNHCO 2 R 5 1; (29) -(CH 2 )pNC(O)NHR 1 (30) -CH 2 )pCO 2 R 5 1 (3 1) -NHR 9 (32) R 30 -(CH 2 )p C R 9 P wherein R 30 and R 3 1 are the same or different, and each p is R 30 R 32 (CHl2)pL-C C R9 independently selected; (33) 1R 31 1 3 wherein R 30, R 31 R 32 and R 33 are the same or different; (34)-alkenyl-CO 2 R 9 a; alkeny1-C(O)R 9 a; (36)-alkenyl-CO 2 R 51 alkenyl-C(O)~R 27 a; (38) (CH 2 )p-alkeny-CO 2 R51; (37) -(CH 2 )pC=NOR 51 and (39) -(CH 2 )p-phthalimid; p isO0, 1, 2, 3 or 4; each R' and R 2 is independently selected from the group consisting of:- H; Halo; -CF 3 -OR' 0 -COR' 0 -SR; 5 wherein t is 0, 1 or 2; N(R' 0 2 -NO 2 (10) -OC(O)R' 0 (11) -CO 2 R' 0 (12) -OCO 2 R 1 5 (13) -CN; (14) NR' 0 COOR' 5 (15) -SR 5 C(O)OR 1 5 (16) -SR 5 N(R1 3 2 provided that R 1 5 in -SR 15 N(R 3 2 is not -CH 2 and wherein each R is independently selected from the group consisting of: H and C(O)OR' 5 (17) benzotriazol- I-yloxy; (18) tetrazol-5-ylthio; (19) substituted ID O (20) alkynyl; (21) alkenyl; and (22) alkyl, said alkyl or alkenyl group optionally being C substituted with halogen, -ORo 0 or -CO2R; O R 3 and R 4 are the same or different and each independently represent H, and any of the 00 substituents of R' and R 2 R 5 R 6 R 7 and R 7 a each independently represent: H, -CF 3 -COR 1 0 alkyl or aryl, said alkyl or aryl optionally being substituted with -S(0)R' 1 5 -NRIoCOOR 1 5 -C(O)RIO; or OS; CO 2 Ro 1 or R 5 is combined with R 6 to represent =0 or =S; IND R 1 1 R 8 is selected from the group consisting of: O0 R 2 1 R1 1a 0/ R 2 2 O=S= O O N O C R 11 R12 R 46 R 9 is selected from the group consisting of: unsubstituted heteroaryl; substituted heteroaryl; arylalkoxy; substituted arylalkoxy; heterocycloalkyl; substituted heterocycloalkyl; heterocycloalkylalkyl; substituted heterocycloalkylalkyl; (9) unsubstituted heteroarylalkyl; (10) substituted heteroarylalkyl; (11) unsubstituted heteroarylalkenyl; (12) substituted heteroarylalkenyl; (13) unsubstituted heteroarylalkynyl and (14) substituted heteroarylalkynyl; wherein said substituted R 9 groups are substituted with one or more substituents selected from the group consisting of: -OH; -CO 2 R 14 -CH20R' 4 halogen; alkyl; amino; trityl; heterocycloalkyl; cycloalkyl; (10) arylalkyl; (11) heteroaryl; (12) heteroarylalkyl and wherein R 14 is independently selected from the group consisting of: H; alkyl; aryl, arylalkyl, heteroaryl and heteroarylalkyl; R9a is selected from the group consisting of: alky and arylalkyl; Rio is selected from the group consisting of: H; alkyl; aryl and arylalkyl; OD R" is selected from the group consisting of: alkyl; substituted alkyl; (3) S unsubstituted aryl; substituted aryl; unsubstituted cycloalkyl; substituted cycloalkyl; O unsubstituted heteroaryl; substituted heteroaryl; heterocycloalkyl; and 00 substituted heterocycloalkyl; wherein said substituted alkyl, substituted cycloalkyl, and substituted heterocycloalkyl R" groups are substituted with one or more substituents selected from the group consisting of: -OH; fluoro; and alkyl; and wherein said substituted \O aryl and substituted heteroaryl R" groups are substituted with one or more substituents independently selected from the group consisting of: -OH; halogen; and alkyl; Ila 0 Ra is selected from the group consisting of: H; OH; alkyl; substituted O 0 10 alkyl; unsubstituted aryl; substituted aryl; unsubstituted cycloalkyl; substituted cycloalkyl; unsubstituted heteroaryl; (10) substituted heteroaryl; (11) heterocycloalkyl; and (12) substituted heterocycloalkyl; wherein said substituted alkyl, substituted cycloalkyl, and substituted heterocycloalkyl R' a groups are substituted with one or more substituents independently selected from the group consisting of: -OH; -CN; -CF 3 (4) fluoro; alkyl; cycloalkyl; heterocycloalkyl; arylalkyl; heteroarylalkyl; alkenyl and (11) heteroalkenyl; and wherein said substituted aryl and substituted heteroaryl RI la groups have one or more substituents independently selected from the group consisting of: (1) -OH; -CN; -CF 3 halogen; alkyl; cycloalkyl; heterocycloalkyl; (8) arylalkyl; heteroarylalkyl; (10) alkenyl; and (11) heteroalkenyl; R 1 2 is selected from the group consisting of: H, alkyl, piperidine Ring V, cycloalkyl, and -alkyl-(piperidine Ring V); R' 5 is selected from the group consisting of: alkyl and aryl; R 2 1 R 22 and R 46 are independently selected from the group consisting of: (2) alkyl; unsubstituted aryl; substituted aryl substituted with one or more substituents independently selected from the group consisting of: alkyl, halogen, CF 3 and OH; unsubstituted cycloalkyl; substituted cycloalkyl substituted with one or more substituents independently selected from the group consisting of: alkyl, halogen, CF 3 and OH; heteroaryl of the formula, N and O and heterocycloalkyl of the formula: IND o V 00 N R 44 wherein R 44 is selected from the group consisting of: alkyl; (c) alkylcarbonyl; alkyloxy carbonyl; haloalkyl; and -C(O)NH(R 1 O 2R is selected from the group consisting of: H; alkyl; alkoxyl; -CH 2 0 CN; R 9 -CH 2 CO 2 H; -C(O)alkyl; and CH 2 CO 2 alkyl; R 27 is selected from the group consisting of: -OH; alkyl; and (4) C' alkoxy; R 27a is selected from the group consisting of: alkyl; and alkoxy; R 30 R R 32 and R 33 are independently selected from the group consisting of: -H; -OH; alkyl; aryl phenyl); arylalkyl benzyl); -OR9a; (8) -NH 2 -NHR 9 a; and (10) -N(R 9 a) 2 wherein each R 9 a is independently selected; R 50 is selected from the group consisting of: alkyl; unsubstituted heteroaryl; (3) substituted heteroary; and amino; wherein said substituents on said substituted R 50 groups are independently selected from the group consisting of: alkyl, halogen, and -OH; R 51 is selected from the group consisting of: H, and alkyl; provided that a ring carbon atom adjacent to a ring heteroatom in a substituted heterocycloalkyl moiety is not substituted with a heteroatom or a halo atom; and provided that a ring carbon atom, that is not adjacent to a ring heteroatom, in a substituted heterocycloalkyl moiety, is not substituted with more than one heteroatom; and provided that a ring carbon atom, that is not adjacent to a ring heteroatom, in a substituted heterocycloalkyl moiety, is not substituted with a heteroatom and a halo atom; and provided that a ring carbon in a substituted cycloalkyl moiety is not substituted with more than one heteroatom; and provided that a carbon atom in a substituted alkyl moiety is not substituted with more than one heteroatom; and provided that the same carbon atom in a substituted alkyl moiety is not substituted with both heteroatoms and halo atoms.
137. 174. The method of claim 173, wherein the compound has the formula: X=CH or N; B is H when the optional bond is present between C-5 and C-6, and when the optional bond between C-5 and C-6 is absent then each B is H.
138. 175. The method of claim 173, wherein the compound has the formula: X=-CH or N; A is H when the optional bond is present between C-5 and C-6, and when the optional bond between C-5 and C-6 is absent then each A is H.
139. 176. The method of claim 173, wherein R' to R 4 are each independently selected from H or halo.
140. 177. The method of claim 173, wherein R 5 to R 7 are H. IO
141. 178. The method of claim 173, wherein a is N and the remaining b, c and d O substituents are carbon. 00
142. 179. The method of claim 173, wherein a, b, c, and d are carbon. O 180. The method of claim 173, wherein the optional bond between C-5 and C-6 is M present. 0 10 181. The method of claim 173, wherein the optional bond between C-5 and C-6 is absent.
143. 182. The method of claim 173, wherein R 8 is group 2.0, or
144. 183. The method of claim 173, wherein one of A and B is H and the other is R 9
145. 184. The method of claim 179, wherein R 9 is selected from the group consisting of: heterocycloalkylalkyl of the formula -(CH 2 )n-heterocycloalkyl; substituted heterocycloalkylalkyl of the formula -(CH 2 )n-substituted heterocycloalkyl; unsubstituted heteroarylalkyl of the formula -(CH 2 )n-heteroaryl; and substituted heteroarylalkyl of the formula -(CH 2 ),-substituted heteroaryl; wherein n is 1, 2, or 3 and the substituents for said substituted R 9 groups are each independently selected from the group consisting of: -OH; -CO 2 R' 4 -CH 2 OR 14 halo, alkyl; amino; trityl; heterocycloalkyl; (8) arylalkyl; heteroaryl and (10) heteroarylalkyl. wherein R 1 4 is independently selected from the group consisting of: H and alkyl.
146. 185. The method of claim 184, wherein R 9 is selected from the group consisting of: -(CH 2 ),-imidazolyl; -(CH 2 )n-substituted imidazolyl; -(CH 2 ),-morpholinyl; (CH 2 )n-substituted morpholinyl, -(CH 2 )n-piperazinyl, and -(CH 2 )n-substituted piperazinyl, wherein n is 1,2, or 3.
147. 186. The method of claim 173, wherein: R" is selected from the group consisting of: alkyl, cycloalkyl and substituted cycloalkyl wherein the substituents are selected from the group consisting of: halo, alkyl and amino; RIla is selected from: alkyl, unsubstituted aryl, 00 N SO, 0 R44 and substituted aryl, cycloalkyl or substituted cycloalkyl, wherein the substituents on said substituted groups are are selected from the group F22 consisting of: halo, -CN or CF 3 R 2 R 2 and R 22 are H; and R 46 is selected from the C group consisting of: unsubstituted aryl, 2247 substituted aryl wherein the substituents are 0 5 selected from the group consisting of: alkyl, alkylcarbonyl and haloalkyl, and wherein R 44 is O IN selected from the group consisting of: H or -C(O)NH 2
148. 187. The method of claim 173, wherein R 8 is selected from the group consisting of: group 2.0 wherein R" is selected from the group consisting of: t-butyl and cyclohexyl; (2) group 3.0 wherein is selected from the group consisting of: methyl and t-butyl; group wherein, R 1 2 is H, and R' a is selected from the group consisting of: t-butyl, cyanophenyl, chlorophenyl, fluorophenyl and cyclohexyl; group 5.0 wherein R 2 and R 22 are H, and R 46 is N+ N selected from the group consisting of: 44 wherein R 44 i -C(O)NH 2
149. 188. The method of claim 187, wherein R 8 is group
150. 189. The method of claim 173, wherein the optional bond between C5 and C6 is present and A is H and B is R 9
151. 190. The method of claim 173, wherein: R' to R 4 are each independently selected from the group consisting of: H and halo; R 6 R 7 and R 7 a are H; a is N and the remaining b, c and d substituents are carbon; the optional bond between C5 and C6 is present; A is H; B is R 9 R 8 is group 2.0 or 4.0; R" is selected from the group ID O consisting of: alkyl, cycloalkyl and substituted cycloalkyl wherein the substituents are selected from the group consisting of: halo, alkyl and amino; R la is selected from the group O consisting of: alkyl, unsubstituted aryl, substituted aryl, cycloalkyl or substituted cycloalkyl, 00 wherein the substituents on said substituted groups are are selected from the group consisting of: halo, -CN and CF 3 (10) R 1 2 is H; (11) R 9 is selected from the group consisting of: (CH 2 )n-heterocycloalkyl; -(CH 2 )n-substituted heterocycloalkyl; -(CH 2 )n-heteroaryl, and -(CH 2 )n-substituted heteroaryl; wherein n is 1, 2, or 3 and the substituents for said c substituted R 9 groups are each independently selected from the group consisting of: -OH; NO -CO 2 RI4; -CH 2 0R 1 4 halo, alkyl; amino; trityl; heterocycloalkyl; (9) 0 10 arylalkyl; (10) heteroaryl and (11) heteroarylalkyl; wherein R 4 is independently selected from the group consisting of: H and alkyl; and (12) X is N or CH.
152. 191. The method of claim 190, wherein: R' to R 4 are each independently selected from H, Br or Cl; R 9 is selected from the group consisting of: -(CH 2 )n-imidazolyl; (b) -(CH 2 )n-substituted imidazolyl; -(CH 2 )n-morpholinyl; -(CH 2 ),-substituted morpholinyl, -(CH 2 )n-piperazinyl, or -(CH 2 )n-substituted piperazinyl, wherein n is 1, 2, or 3; R' is selected from the group consisting of: t-butyl and cyclohexyl; R 1 2 is H; and Rlais selected from the group consisting of: t-butyl, cyanophenyl, chlorophenyl, fluorophenyl and cyclohexy.
153. 192. The method of claim 191, wherein: R' and R 2 are H; R 3 is H; R 4 is Cl; R 8 is 4.0 wherein R la is cyanophenyl; and R 1 2 is H; and R 9 is selected from the group consisting of: -CH 2 -imidazolyl, and -CH 2 -imidazolyl wherein said imidazolyl moiety is substituted with a methyl group.
154. 193. The method of claim 192, having the formula:
155. 194. The method of claim 193, wherein X is N.
156. 195. A method of claim 173, wherein the compound is of the formula: B 5 6 (RA) d Z (R wherein: one of a, b, c and d represents N or NO and the remaining a, b, c, and d groups represent CR' wherein each R' group on each carbon is the same or different; or each a, b, c, and d group represents CR' wherein each R' group on each carbon is the same or different; ID O the dotted lines represent optional bonds; X represents N or CH when the optional bond to C11 is absent, and represents C O when the optional bond to C 11 is present; 00 R' is selected from the group consisting of: H; halo; -CF 3 -OR 1 0 COR"o; -SRIo; -S(O)tR 15 -NO 2 (10) (11) CO 2 RI 0 (12) -OCO 2 R 0 (13) -CN; (14) -NR'OCOOR"; (15) -SR'iC(O)OR"; (16) R SR 15 N(R 1 3 2 wherein each R 1 3 is independently selected from the group consisting of: H and C(O)OR 15 and provided that R 1 5 in -SR15N(R 3 2 is not -CH 2 (17) benzotriazol-1-yloxy; NO (18) tetrazol-5-ylthio; (19) substituted tetrazol-5-ylthio; (20) alkynyl; (21) alkenyl; (22) alkyl; 0 10 (23) alkyl substituted with one or more substitutents independently selected from the group consisting of: halogen, -OR 1 0 and -CO 2 R 0 (24) alkenyl substituted with one or more substitutents independently selected from the group consisting of: halogen, -OR 1 0 and CO 2 Ri0; Each R is independently selected from the group consisting of: halo; -CF 3 -ORo; COR 1 0 -SR10; 2 -NO 2 -OC(O)Ro 0 CO 2 R 0 (11) -OCO 2 RI 0 (12) -CN; (13) -NRI°COORi 5 (14) -SRsC(O)OR; -SR'"N(R' 3 2 wherein each R 1 3 is independently selected from the group consisting of: H and -C(O)OR 1 5 and provided that R 15 in -SR5N(R 3 2 is not -CH 2 (16) benzotriazol-1-yloxy; (17) tetrazol-5-ylthio; (18) substituted tetrazol-5-ylthio; (19) alkynyl; (20) alkenyl; (21) alkyl; (22) alkyl substituted with one or more substitutents independently selected from the group consisting of: halogen, -OR 1 0 and -CO 2 R 1 0 and (23) alkenyl substituted with one or more substitutents independently selected from the group consisting of: halogen, -OR 1 0 and C02R10; CO 2 Rio m is 0, 1 or 2; t is 0, 1 or 2 R s R 6 R 7 and R 7a are each independently selected from the group consisting of: (1) H; -CF 3 -COR 1 alkyl; unsubstituted aryl; alkyl substituted with one or more groups selected from the group consisting of: -OR 0 -SRo1, -S(O)tR 1 NR'iCOOR' 1 -N(R' 0 2 -NO 2 -C(O)RO; -OCORO, -OCO 2 R 5 CO 2 R 0 and OPO 3 R 0 and aryl substituted with one or more groups selected from the group consisting of: -OR 1 0 -SR' i -NROCOOR' 5 -N(R' 0 )2'-NO 2 -C(O)R i -OCORio, -OCO 2 R" 5 -CO 2 R' 0 and OPO 3 Ri 0 or R 5 together with R 6 represents =0 or =S; R 8 is selected from the group consisting CD O R 11 of: 0 0 R11 R12 S R 2 1 R 2 2 0 C SR46 R 1 0 is selected from the group consisting of: H; alkyl; aryl and arylalkyl; R" is selected from: alkyl; substituted alkyl; unsubstituted aryl; substituted aryl; unsubstituted cycloalkyl; substituted cycloalkyl; unsubstituted heteroaryl; substituted heteroaryl; heterocycloalkyl; and (10) substituted heterocycloalkyl; wherein said substituted alkyl, substituted cycloalkyl, and substituted heterocycloalkyl groups are substituted with one or more substituents selected from the group consisting of: -OH; fluoro; and alkyl; and wherein said substituted aryl and substituted heteroaryl R" groups are substituted with one or more substituents selected from the group consisting of: -OH; halogen; and alkyl; R lais selected from the group consisting of: H; OH; alkyl; substituted alkyl; unsubstituted aryl; substituted aryl; unsubstituted cycloalkyl; substituted cycloalkyl; unsubstituted heteroaryl; (10) substituted heteroaryl; (11) heterocycloalkyl; and (12) substituted heterocycloalkyl; wherein said substituted alkyl, substituted cycloalkyl, and substituted heterocycloalkyl R i la groups are substituted with one or more substituents selected from the group consisting of: -OH; -CN; -CF 3 fluoro; alkyl; (6) cycloalkyl; heterocycloalkyl; arylalkyl; heteroarylalkyl; (10) alkenyl and (11) heteroalkenyl; and wherein said substituted aryl and substituted heteroaryl R la groups are substituted with one or more substituents selected from the group consisting of: -OH; (2) -CN; -CF 3 halogen; alkyl; cycloalkyl; heterocycloalkyl; arylalkyl; (9) heteroarylalkyl; (10) alkenyl and (11) heteroalkenyl; R 12 is selected from the group consisting of: H, alkyl, piperidine Ring V, cycloalkyl, and -alkyl-(piperidine Ring V); R 1 5 is selected from the group consisting of: alkyl and aryl; R 2 1 R 22 and R 46 are independently selected from the group consisting of: H; (2) alkyl; unsubstituted aryl; substituted aryl substituted with one or more substituents ID O selected from the group consisting of: alkyl, halogen, CF 3 or OH; unsubstituted cycloalkyl; S substituted cycloalkyl substituted with one or more substituents selected from the group 00 N consisting of: alkyl, halogen, CF 3 or OH; heteroaryl of the formula, V S• O N N\ piperidine Ring V: R 44 wherein R 44 is selected from the group consisting of: H, alkyl; alkylcarbonyl; alkyloxy carbonyl; haloalkyl and C(O)NH(R 51 R s 5 is selected from the group consisting of: -H and alkyl methyl, ethyl, propyl, butyl and t-butyl); B is the group: R 3 0 (CH 2 )p C R 9 R 31 P R 3 0 S- C R 9 in said B group: p of the -(CH 2 moiety is 0; p of the P C R9 R 31 moiety is 1 to 3; when p is one for the moiety P then R 30 is selected from the group consisting of: -OH and -NH 2 and R 31 is alkyl; when p is 2 or 3 for the moiety c-D N 0 C R9 R31 P then: for one -CR 30 R 31 moiety, R 30 is selected from the group consisting of: -OH and -NH 2 and R 3 1 is alkyl; and for the remaining -CR 30 R 31 N moieties R 30 and R 3 1 are hydrogen; and R 9 is unsubstituted heteroaryl or substituted heteroaryl, provided that when said heteroaryl group contains nitrogen in the ring, then said heteroaryl group is not bound by a ring nitrogen to the adjacent -CR 3 0 R 3 moiety when R 30 C is -OH or -NH 2
157. 196. The method of claim 195, wherein: a is N; b, c and d are CR' groups wherein all of said R' substituents are H, or one R' substituent is halo and the remaining two R' substituents are hydrogen; m is 1, and R 3 A is halo, or m is 2 and each R 3 A is the same or different halo Br or Cl); and R s R 6 R 7 and R 7 a are H.
158. 197. A method claim 173, wherein the compound is of the formula: B 8 a R wherein: R 3 0 (CH 2 )p C R 9 P B is the group: in said B group: p of the -(CH 2 moiety is 0; p of the 'P C R 9 R 3 1 moiety is 1 to 3; when p is one for the moiety P then R 30 is selected from the group consisting of: -OH and -NH 2 and R 3 1 is alkyl; when p is 2 or 3 for the moiety SR 30 C R 9 R 31 P then: for one -CR 30 R 31 moiety, R 30 is selected from the group consisting of: -OH and -NH 2 and R 31 is alkyl; and for the remaining -CR 3 0 R 3 moieties R 30and R 3 1 are hydrogen; and R 9 is unsubstituted heteroaryl or substituted heteroaryl, provided that when said heteroaryl group contains nitrogen in the ring, then said heteroaryl group is not bound by a ring nitrogen to the adjacent -CR 3 0 R 3 1 moiety when R 30 is -OH or -NH 2 a is N; b, c and d are CR' groups wherein all of said R' substituents are H, or one R' substituent is halo and the remaining two R' substituents are hydrogen; m is 1, and R 3 A is halo, or m is 2 and each R 3A is the same or different halo; X is N or CH; R 5 R 6 R 7 and R 7 a are H; OD S(H) R 8 is selected from the group consisting of: C) O R 11 a RI O= S= O O N I R 11 I 00 R 1 12 R 2 1 R22 ON R 0 SR46 Cl R' is selected from: alkyl; substituted alkyl; unsubstituted aryl; (4) substituted aryl; unsubstituted cycloalkyl; substituted cycloalkyl; unsubstituted heteroaryl; substituted heteroaryl; heterocycloalkyl; and (10) substituted heterocycloalkyl; wherein said substituted alkyl, substituted cycloalkyl, and substituted heterocycloalkyl R" groups are substituted with one or more substituents selected from the group consisting of: -OH; fluoro; and alkyl; and wherein said substituted aryl and substituted heteroaryl R 1 groups are substituted with one or more substituents selected from the group consisting of: -OH; halogen; and alkyl; R la is selected from the group consisting of: H; OH; alkyl; substituted alkyl; unsubstituted aryl; substituted aryl; unsubstituted cycloalkyl; substituted cycloalkyl; unsubstituted heteroaryl; (10) substituted heteroaryl; (11) heterocycloalkyl; and (12) substituted heterocycloalkyl; wherein said substituted alkyl, substituted cycloalkyl, and substituted heterocycloalkyl R i a groups are substituted with one or more substituents selected from the group consisting of: -OH; -CN; -CF 3 fluoro; alkyl; (6) cycloalkyl; heterocycloalkyl; arylalkyl; heteroarylalkyl; (10) alkenyl and (11) heteroalkenyl; and wherein said substituted aryl and substituted heteroaryl R' Ia groups are substituted with one or more substituents selected from the group consisting of: -OH; (2) -CN; -CF 3 halogen; alkyl; cycloalkyl; heterocycloalkyl; arylalkyl; (9) heteroarylalkyl; (10) alkenyl and (11) heteroalkenyl; R 1 2 is selected from the group consisting of: H, alkyl, piperidine Ring V, cycloalkyl, and -alkyl-(piperidine Ring V); R 2 1 R 22 and R 46 are independently selected from the group consisting of: H; (2) alkyl; unsubstituted aryl; substituted aryl substituted with one or more substituents selected from the group consisting of: alkyl, halogen, CF 3 or OH; unsubstituted cycloalkyl; substituted cycloalkyl substituted with one or more substituents selected from the group consisting of: alkyl, halogen, CF 3 or OH; heteroaryl of the formula, 0 piperidine Ring V: v N R 44 wherein R 44 is selected from the group consisting of: H, alkyl; alkylcarbonyl; alkyloxy carbonyl; haloalkyl and C(O)NH(R 51 and R 51 is selected from the group consisting of: H and alkyl methyl, ethyl, propyl, butyl and t-butyl).
159. 198. The method of claim 197, wherein: in the B group: p of the P moiety is 0; p of the P moiety is 1 to 2; when p is one for the moiety P then R 30 is selected from the group consisting of: -OH and -NH 2 and R 31 is CI-C 2 alkyl; when p is 2 or 3 for the moiety P then: IO S(1) for one -CR3R 3 1 moiety, R 3 0 is selected from the group consisting of: -OH and C NH 2 and R 3 1 is CI-C 2 alkyl; and for the remaining -CR 0 R 31 moieties R 3 0 and R 31 are S hydrogen; and R 9 is imidazolyl or substituted imidazolyl, provided that said imidazolyl 00 group is not bound by a ring nitrogen to the adjacent -CR 3 0 R 31 moiety when R 30 is -OH or -NH 2 R 8 is R' is alkyl; S(D) Xis N; s b, c and d are CR' groups wherein all of said R' substituents are H; m is 1, and R 3 A is halo; and X is N.
160. 199. The method of claim 198, wherein the B group: p of the -(CH 2 moiety R 30 S- C R 9 R 31 is 0; p of the P moiety is 1; R 30 is selected from the group consisting of: -OH and -NH 2 and R 31 is Ci-C 2 alkyl; and R 9 is substituted imidazolyl wherein said the substituent is an alkyl group, provided that said imidazolyl group is not bound by a ring nitrogen to the adjacent -CR 3 0 R 31 moiety.
161. 200. The method of claim 199, wherein: R 30 C R 9 R 3 1 in said B group: p of the -(CH 2 moiety is 0; p of the P moiety is 1; R 30 is -OH, and R 3 1 is methyl; and R 9 is substituted imidazolyl wherein the substituent is a methyl group, provided that said imidazolyl group is not bound by a ring nitrogen to the adjacent -CR 3 0 R 31 moiety; and R 3 A is Cl; and R" is alkyl. 375 IO c
162. 201. The method of claim 200, wherein R 9 is O IND 202. The method of claim 201, wherein R" is t-butyl.
163. 203. The method of claim 183, wherein the compound is of the formula: B 6 (R3A)m II Jl N R7 IV ROR7a N wherein all substituents are as defined for claim 376
164. 204. The method of claim 197, wherein the compound is of the formula: wherein all substituents are as defined in claim 197.
165. 205. The method of claim 197, wherein the compound is of the formula: ,(R 3 A)m R wherein all substituents are as defined in claim 183.
166. 206. The method of claim 204, wherein: c R 30 CR 00 R 31 in the B group: p of the -(CH 2 moiety is 0; p of the P moiety is 1; R 30 is -OH, and R 3 1 is methyl; and R 9 is substituted imidazolyl wherein the substituent is a methyl group, provided that said imidazolyl group is not bound by a ring nitrogen to the adjacent -CR 30 R 31 moiety; and (B)R A is Cl; and S(C) R"is alkyl.
167. 207. The method of claim 203, wherein R 9 is H 3 C N N
168. 208. The method of claim 201, wherein R" is t-butyl.
169. 209. The method of claim 205, wherein: R 3 0 CR in the B group: p of the -(CH 2 moiety is 0; p of the P moiety is 1; R 30 is -OH, and R 31 is methyl; and R 9 is substituted imidazolyl wherein the substituent is a methyl group, provided that said imidazolyl group is not bound by a ring nitrogen to the adjacent -CR 3 0 R 31 moiety; and R 3A is Cl; and R" is alkyl. 378
170. 210. The method of claim 209, wherein R 9 is H 3 C N
171. 211. The method of claim 210, wherein R" is t-butyl.
172. 212. A method of treating a synucleinopathic subject, the method comprising, administering to a synucleinopathic subject a farnesyl transferase inhibitor compound of the formula: or a stereoisomeric form, or a pharmaceutically acceptable acid or base addition salt form thereof, in a therapeutically effective amount, wherein: one of a, b, c and d represents N or N+O and the remaining a, b, c, and d groups represent carbon, wherein each carbon has an R' or R 2 group bound to said carbon; or each of a, b, c, and d is carbon, wherein each carbon has an R' or R 2 group bound to said carbon; IO the dotted lines represent optional bonds; X represents N or CH when the optional bond is absent, and represents C when the O optional bond is present; 00 when the optional bond is present between carbon atom 5 and carbon atom 6 then there is only one A substituent bound to carbon atom 5 and there is only one B substituent bound to carbon atom 6 and A or B is other than H; O when the optional bond is not present between carbon atom 5 and carbon atom 6, then there c are two A substituents bound to carbon atom 5 and two B substituents bound to carbon NO atom 6, wherein each A and B substituent is independently selected from the group O 0 10 consisting of: -R9; -R9-CO 2 -R9a; -(CH 2 )pR26; C(O)N(R 9 2 wherein each R 9 is the same or different; -C(O)NHR 9 -C(O)NH- CH 2 -C(O)-NH 2 -C(O)NHR 26 (10) -(CH 2 )pC(R 9 R 9 a; (11) -(CH 2 )p(R 9 2 wherein each R 9 is the same or different; (12) (CH 2 )pC(O)R 9 (13) -(CH 2 )pC(O)R 27 a; (14) -(CH 2 )pC(O)N(R 9 2 wherein each R 9 is the same or different; (15) (CH 2 )pC(O)NH(R 9 (16) (CH 2 )pC(O)N(R 26 2 wherein each R 26 is the same or different; (17) -(CH 2 )pN(R 9 )-R 9 a; (18)-(CH 2 )pN(R 26 2 wherein R 26 is the same or different; (19) -(CH 2 )pNHC(O)Rs 0 (20) -(CH 2 )pNHC(0) 2 R 5 0 (21) (CH 2 )pN(C(O)R 27 a) 2 wherein each R 27a is the same or different; (22) (CH 2 )pNR 5 1 C(O)R 27 or R 51 and R 27 taken together with the atoms to which they are bound form a heterocycloalkyl ring consisting of, 5 or 6 members, provided that when R 51 and R 27 form a ring, R 51 is not H; (23) (CH 2 )pNRsC(O)NR27, or R 5 and R 27 taken together with the atoms to which they are bound form a heterocycloalkyl ring consisting or 5 or 6 members, provided that when R 51 and R 27 form a ring, R 51 is not H; (24) -(CH 2 )pNR 5 'C(O)N(R 27 a) 2 wherein each R 27 a is the same or different; (25) -(CH 2 )pNHS02N(R 51 2 wherein each R 5 is the same or different; (26) (CH 2 )pNHCO 2 R 0 (27) -(CH 2 )pNC(O)NHR 1 (CH 2 )pCO 2 R 5 1 (29) -NHR 9 R 3 0 (CH 2 )p C R 9 R 31 P wherein R 30 and R are the same or different; (31) R 30 R 32 C -(CH 2 )p-C-C-R 9 0 00 R 31 R 33 wherein R 3 0 R 3 1 R 32 and R 33 are the same or different; (32) alkenyl-CO 2 R 9 a; (33) -alkenyl- C(O)R 9 a; (34) -alkenyl-CO 2 R 5 1 (35) -alkenyl-C(O)-R 27 a; (36) (CH 2 )p-alkenyl- C0 2 -R 5 1 (37) -(CH 2 )pC=NOR and (38) -(CH 2 )p-Phthalimid; p is 0, 1, 2, 3 or 4; each R' and R 2 is independently selected from H, Halogen, -CF 3 -ORI 0 COR" 0 SR", 5 wherein t is 0, 1 or 2, -N(R' 0 2 -NO 2 -OC(O)R'O, CO 2 R'o, -OCO 2 R1 5 -CN, -NR'oCOOR", -SR"C(O)OR"'-SR 5 N(R' 3 )2 provided that in -SR' 5 N(R' 3 2 is not -CH 2 and wherein each R' 3 is independently selected from H or -C(O)OR 5 benzotriazol-1-yloxy, tetrazol-5-ylthio, or substituted tetrazol-5-ylthio, alkynyl, alkenyl or alkyl, said alkyl or alkenyl group optionally being substituted with halogen, -OR' 0 or CO 2 R R 3 and R 4 are the same or different and each independently represent H, or any of the substituents of R' and R 2 RS, R6, R7 and R 7 a each independently represent H, -CF 3 -CORIo, alkyl or aryl, said alkyl or aryl optionally being substituted with -OR' 0 -SRo, 5 NR'oCOOR'S, N(R" 0 2 -NO 2 -OCORo, -OCO 2 CO 2 R'O, OPO 3 RO, or R' is combined with R6 to represent -0 or =S; R 8 is selected from the group consisting of: R21 Rlla R22 O= S= OO N O C R11 H, O R" R 1 2 R R 9 is selected from the group consisting of: heteroaryl; substituted heteroaryl; (3) arylalkoxy; substituted arylalkoxy; heterocycloalkyl; substituted heterocycloalkyl; heterocycloalkylalkyl; substituted heterocycloalkylalkyl; (9) heteroarylalkyl; (10) substituted heteroarylalkyl; (11) heteroarylalkenyl; (12) substituted heteroarylalkenyl; (13) heteroarylalkynyl; (14) substituted heteroarylalkynyl; (16) substituted arylalkyl; (17) alkenyl, and (18) substituted alkenyl; wherein said substituted R 9 groups are substituted with one or more substituents selected from the group ID consisting of: -OH; -CO 2 R1 4 -CH 2 OR 4 halogen; alkyl; amino; trityl; heterocycloalkyl; cycloalkyl; (10) arylalkyl; (11) heteroaryl; (12) O heteroarylalkyl and (13) O wherein f* 5 R 14 is independently selected from the group consisting of: H; alkyl; aryl, arylalkyl, (N \O heteroaryl and heteroarylalkyl; O R 9a is selected from the group consisting of: alky and arylalkyl; R i o is selected from the group consisting of: H; alkyl; aryl and arylalkyl; R" is selected from the group consisting of: alkyl; substituted alkyl; aryl; (4) substituted aryl; cycloalkyl; substituted cycloalkyl; heteroaryl; (8) substituted heteroaryl; heterocycloalkyl; and (10) substituted heterocycloalkyl; wherein said substituted R" groups have 1,2 or 3 substituents selected from the group consisting of: -OH; halogen and alkyl; R'tais selected from the group consisting of: H; OH; alkyl; substituted alkyl; aryl; substituted aryl; cycloalkyl; substituted cycloalkyl; heteroaryl; substituted heteroaryl; (11) heterocycloalkyl; and (12) substituted heterocycloalkyl; wherein said substituted R' a groups have one or more substituents selected from the group consisting of: -OH; -CN; CF 3 halogen; alkyl; cycloalkyl; (7) heterocycloalkyl, arylalkyl; heteroarylalkyl; (10) alkenyl and (11) heteroalkenyl; R 1 2 is selected from the group consisting of: H, and alkyl; R 1 5 is selected from the group consisting of: alkyl and aryl; R 21 R 22 and R 46 are independently selected from the group consisting of: alkyl; aryl; substituted aryl, optionally substituted with one or more substituents selected from the group consisting of: alkyl, halogen, CF 3 and OH; cycloalkyl; substituted cycloalkyl; optionally substituted with one or more substituents selected from the group consisting of: alkyl, halogen, CF 3 and OH; heteroaryl of the formula, 0 o V 00 and 0; and heterocycloalkyl of the formula: R 44 wherein R 44 is selected from the group consisting of: alkyl; alkylcarbonyl; alkyloxy tF- O carbonyl; haloalkyl and -C(O)NH(R 1 when R 2 1 R 22 or R 4 6 is the C heterocycloalkyl of the formula above, Ring V is selected from the group consisting of: N R 44 44 R44, N N I N I CH 3 C(O)CH 3 C(O)CH 3 N \CN C02C2H5, C(0)NH2 and CO2-t-BUTYL; R 2 6 is selected from the group consisting of: alkyl; alkoxyl; -CH 2 CN; R 9 -CH 2 CO 2 H; -C(O)alkyl and CH 2 CO 2 alkyl; R 27 is selected from the group consisting of: -OH; alkyl and alkoxy; R 27 ais selected from the group consisting of: alkyl and alkoxy; R 30 through R 33 are independently selected from the group consisting of: OH; alkyl; aryl and arylalkyl; R 5 0 is selected from the group consisting of: alkyl; heteroaryl; substituted heteroaryl and amino; wherein said substituents on said substituted R 50 groups are independently selected from the group consisting of: alkyl; halogen; and OH; ROa is selected from the group consisting of: heteroaryl; substituted heteroaryl and amino; R 51 is selected from the group consisting of: and alkyl.
173. 213. The method of claim 212, wherein the compound is a compound shown in Figure 6.
174. 214. The method of claim 212, wherein the compound is a compound shown in Figure 7.
175. 215. A method of treating a synucleinopathic subject, the method comprising, administering to a synucleinopathic subject a farnesyl transferase inhibitor compound of the formula: X 4 X1 x2 I x X 3 R6 R R N N NR 19 R 20 Y 2 or a stereoisomeric form, or a pharmaceutically acceptable acid or base addition salt form thereof, in a therapeutically effective amount, wherein: A represents N or N-oxide; o X represents N, CH or C, such that when X is N or CH, there is a single bond to carbon atom 11 as represented by the solid line; or when X is C, there is a double bond to O carbon atom 11, as represented by the solid and dotted lines; 00 X' and X 2 are independently selected from bromo or chloro, and X 3 and X 4 are independently selected from hydrogen, bromo or chloro provided that at least one of X 3 and X 4 is hydrogen; Y and Y 2 are independently selected from hydrogen or alkyl; Z is =0 or =S; R 5 R R 7 and R 8 each independently represents hydrogen, CF 3 COR 10 alkyl or 0 10 aryl, and further wherein R 5 may be combined with R 6 to represent =0 or =S and/or R 7 may be combined with R 8 to represent =0 or =S; R I0 R 1 9 and R 20 independently represent hydrogen, alkyl, alkoxy, aryl, aralkyl, heteroaryl, heteroarylalkyl, cycloalkyl, cycloalkylalkyl, heterocycloalkyl and heterocycloalkylalkyl, with the proviso that R 1 9 and R 20 are not both hydrogen; v is zero, 1, 2 or 3; and w is zero or 1.
176. 216. The method of claim 215, wherein there is a single bond at carbon atom 11, X is CH, Z is =0 and R 5 R 6 R 7 and R 8 are hydrogen.
177. 217. The method of claim 216, wherein X' is bromo, X 2 is chloro, X 3 is bromo and X 4 is hydrogen.
178. 218. The method of claim 217, wherein Z is v is 1, w is 1, and Y' and Y 2 are hydrogen.
179. 219. The method of claim 218, wherein R 1 9 a nd R 20 are independently selected from hydrogen, aryl and heterocycloalkyl wit h the proviso that R 1 9 and R 20 are not both hydrogen.
180. 220. The method of claim 219, wherein; the aryl group is substituted with alkoxy; and the heterocycloalkyl group is substituted with COOR'O wherein R 1 0 is hydrogen or alkyl.
181. 221. The method of claim 215, wherein there is a single bond at carbon atom 11, X is CH, Z is R 5 R 6 R 7 and R 8 are hydrogen, X' is bromo, X 2 is chloro, X 3 is bromo and X 4 is ID O hydrogen, v is 1, w is 1, and Y' and Y 2 are hydrogen, R 1 9 and R 20 are independently selected S from hydrogen, aryl and heterocycloalkyl; wherein the aryl group is substituted with alkoxy; S and the heterocycloalkyl group is substituted with COOR' 1 wherein Ro 1 is hydrogen or alkyl, 00 with the proviso that R 1 9 and R 20 are not both hydrogen.
182. 222. The method of claim 215, wherein the compound is a compound shown in SFigure 8. (c NO 223. The method of claim 215, wherein the compound is a compound shown in 0 10 Figure 9.
183. 224. The method of claim 215, wherein there is a single bond at carbon atom 11, X is CH, Z is =0 and R 5 R 6 R 7 and R 8 are hydrogen.
184. 225. The method of claim 224, wherein X' is bromo, X 2 is chloro, X 3 is bromo and X 4 is hydrogen.
185. 226. The method of claim 225, wherein Z is v is 1, w is 1, and Y' and Y 2 are hydrogen.
186. 227. The method of claim 226, wherein R 1 9 and R 20 are independently selected from hydrogen, alkyl, aryl and heterocycloalkyl with the proviso that R 9 and R 20 are not both hydrogen.
187. 228. The method of claim 226, wherein the alkyl group is substituted with -OR 1 0 alkoxy, -OCOR 1 0 -CONRi'R' 2 or -COOR 1 0 wherein R1 0 and R 12 are independently selected from hydrogen, alkyl or alkoxy; the aryl group is substituted with alkoxy; and the heterocycloalkyl group is substituted with -COOR 1 0 wherein R 10 is hydrogen or alkyl.
188. 229. The method of claim 215, wherein there is a single bond at carbon atom 11, X is CH, Z is R 5 R 6 R 7 and R 8 are hydrogen, X' is bromo, X 2 is chloro, X 3 is bromo and X 4 is hydrogen, v is 1, w is 1, and Y' and Y 2 are hydrogen, R' 9 and R 20 are independently selected from hydrogen, alkyl, aryl and heterocycloalkyl, wherein the alkyl group is substituted with OR' 0 alkoxy, -OCOR O -CONR'RR 1 2 or -COOR 1 0 wherein R 1 0 and R 1 2 are independently t- O C-q O S 10 (-N selected from hydrogen, alkyl or alkoxy; the aryl group is substituted with alkoxy; the heterocycloalkyl group is substituted with -COOR' 1 wherein R' i is hydrogen or alkyl, with the proviso that R 1 9 and R 20 are not both hydrogen.
189. 230. The method of claim 215, wherein X is CH and Z is =0.
190. 231. The method of claim 215, wherein X is CH, Z is R 5 R 6 R 7 and R 8 are hydrogen, and X' is bromo.
191. 232. A method of treating a synucleinopathic subject, the method comprising, administering to a synucleinopathic subject a farnesyl transferase inhibitor compound of the formula: or a stereoisomeric form, or a pharmaceutically acceptable acid or base addition salt form thereof, in a therapeutically effective amount, wherein: R and R 2 are independently selected from halo; R' and R 3 are independently selected from the group consisting of H and halo, provided that at least one ofR' and R 3 is H; W is N, CH or C, when the double bond is present at the C-11 position; R' is or R 5 R 5 is R6 R 6 R6 N X\ 0 R 6 and R 7 are independently selected from the group consisting of H, alkyl, substituted alkyl, acyl, aryl, aralkyl, heterocycloalkyl and heteroaryl; X is =0 or =S; Z' and Z 2 are independently =0 or =S; n and n 3 are independently 0, 1 or 2; and nl and n2 are independently 0 or 1.
192. 233. The method of claim 232, wherein X is =0 and R 6 and R 7 are each hydrogen.
193. 234. The method of claim 233, wherein n is 1 and n 3 is 0 or 1. \O
194. 235. The method of claim 232, wherein R is bromo and R 2 is chloro or bromo. C) O 0 00 236. The method of claim 235, wherein R is bromo and R 2 is chloro or bromo.
195. 237. The method of 232, wherein R is bromo, R 2 is chloro or bromo, R' is H, and R 3 is chloro or bromo. \O c, I 238. The method of claim 234, wherein R is bromo, R 2 is chloro or bromo, R is H, O 3 and R is chloro or bromo.
196. 239. The method of claim 234, wherein R is bromo, R 2 is chloro or bromo, R 3 is H, and R' is chloro or bromo.
197. 240. The method of claim 234, wherein R is bromo, R 2 is chloro or bromo, R 3 is H, and R' is chloro or bromo.
198. 241. The method of claim 232, wherein the compound is selected from the group consisting of Br C
199. 242. A method of treating a synucleinopathic subject, the method comprising, administering to a synucleinopathic subject a faresyl transferase inhibitor compound of the formula: or a stereoisomeric form, or a pharmaceutically acceptable acid or base addition salt form thereof, in a therapeutically effective amount, wherein: a represents N and the remaining b, c and d groups represent CR' or CR2 R' is selected from H or halo; R 2 is selected from NO 2 Br, Cl or I; 390 OD R 3 is C; R 4 is H or halo; O R R 6 R R 7 and R 8 are H; 00 the dotted line between carbon atoms 5 and 6 represents an optional double bond, such that when a double bond is present, A and B independently represent H, and when no double bond is present between carbon atoms 5 and 6, A and B each independently Srepresent H2; R 20 and R 2 1 are independently selected from H or alkyl; SR 46 is selected from: pyridyl, pyridyl N-oxide or piperidine Ring V: wherein R s0 represents alkyl, alkylcarbonyl, alkyloxycarbonyl, haloalkyl, or C(O)NH(R' i wherein R' 1 is H or alkyl; and Z represents O.
200. 243. The method of claim 242, wherein R' is H.
201. 244. The method of claim 242, wherein R 2 is selected from Br, Cl or I.
202. 245. The method of claim 242, wherein R 2 is Br at the C-3 position.
203. 246. The method of claim 242, wherein R 2 is Br at the C-3 position and R 3 is at the C- 8 position.
204. 247. The method of claim 242, wherein both R 2 0 and R are hydrogen, or both R 20 and R 21 are alkyl.
205. 248. The method of claim 242, wherein both R 20 and R 2 1 are hydrogen.
206. 249. The method of claim 242, wherein R 4 6 is selected from 3-pyridyl, 4-pyridyl, 3- pyridyl N-oxide, 4-pyridyl N-oxide, 4-N-methyl piperidinyl, 3-N-methylpiperidinyl, 4-N- acetylpiperidinyl or 3-N-acetylpiperidinyl. O S10 1O O4
207. 250. The method of claim 242, wherein R 46 is selected from: 3-pyridyl, 4-pyridyl, 3- pyridyl N-oxide, or 4-pyridyl N-oxide.
208. 251. The method of claim 242, wherein R 46 is selected from 4-pyridyl or 4-pyridyl N- oxide.
209. 252. The method of claim 242, wherein the compound is a compound shown in Figure
210. 253. The method of claim 242, wherein the compound is a compound shown in Figure 11.
211. 254. The method of claim 242, wherein the compound is of the formula: A .B wherein: R' is selected from H or halo; R 2 is selected from CH 3 Br, or I; R 3 is C1; R 4 is H or halo; R 5 R 6 R 7 and R 8 are H; ID o the dotted line between carbon atoms 5 and 6 represents an optional double bond, such that when a double bond is present, A and B independently represent.H, and when no O double bond is present between carbon atoms 5 and 6, A and B each independently 00 represent H 2 R 20 and R 2 1 are H; R 46 is selected from: pyridyl, pyridyl N-oxide, triazolyl, 1-N-methylpiperazinyl, (N /S()t ION -wherein t is 0, 1 or 2, or piperidine Ring V: N- R5 0 wherein R 50 represents alkyl, alkylcarbonyl, alkoxycarbonyl, haloalkyl, or C(O)NH(Ro 1 wherein R 1 0 is H or alkyl; and Z represents O.
212. 255. The method of claim 254, wherein R' is H.
213. 256. The method of claim 254, wherein R 2 is selected from Br.
214. 257. The method of claim 254, wherein R 2 is Br and R 3 is at the C-8 position.
215. 258. The method of claim 254, wherein R 4 6 is selected from 3-pyridyl, 4-pyridyl, 3- pyridyl N-oxide, 4-pyridyl N-oxide, 4-N-methyl piperidinyl, 3-N-methylpiperidinyl, 4-N- acetylpiperidinyl or 3-N-acetylpiperidinyl.
216. 259. The method of claim 255, wherein R 46 is selected from: 3-pyridyl, 4-pyridyl, 3- pyridyl N-oxide, or 4-pyridyl N-oxide.
217. 260. The method of claim 255, wherein R 46 is selected from 4-pyridyl or 4-pyridyl N- oxide.
218. 261. The method of claim 255, wherein the compound is a compound shown in Figure 12.
219. 262. The method of claim 267, wherein the compound is a compound shown in Figure 13.
220. 263. The method of claim 261, wherein the compound is a compound shown in Figure 14.
221. 264. A method of treating a synucleinopathic subject, the method comprising, administering to a synucleinopathic subject a famesyl transferase inhibitor compound of the formula: \O O S 10 (-N wherein: R' is selected from H or halo; R 2 is Cl; R 3 is Cl; R 4 is H or halo; R 5 R 6 R 7 and R 8 are H; the dotted line between carbon atoms 5 and 6 represents an optional double bond, such that when a double bond is present, A and B independently represent H, and when no double bond is present between carbon atoms 5 and 6, A and B each independently represent H 2 R 20 and R 2 1 are H; \O C1- 1O S 10 R 46 is selected from: 4-pyridyl N-oxide, 4-pyridyl or piperidine Ring V: wherein R 5 0 represents alkyl, alkylcarbonyl, alkyloxycarbonyl, haloalkyl, or C(O)NH(R' i wherein R' 1 is H or alkyl; and Z represents O.
222. 265. The method of claim 262, wherein R' is H.
223. 266. The method of claim 264, wherein R 3 is at the C-8 position.
224. 267. The method of claim 264, wherein R 46 is selected from 4-pyridyl N-oxide, 4-N- methyl piperidinyl, or 3-N-methylpiperidinyl.
225. 268. The method of claim 264, wherein the compound is a compound shown in Figure
226. 269. A method of treating a synucleinopathic subject, the method comprising, administering to a synucleinopathic subject a famesyl transferase inhibitor compound of the formula: R48 R4 O A B R21\ R°R R 1 R 2 wherein: a represents N and the remaining b, c and d groups represent CR' or CR 2 R' and R 2 are independently selected from H, halo, CF 3 lower alkyl or benzotriazol-1- yloxy; R 3 and R 4 are independently selected from H or halo; R 5 R 6 R 7 and R 8 are H; the dotted line between carbon atoms 5 and 6 represents an optional double bond, such that when a double bond is present, A and B independently represent H, and when no double bond is present between carbon atoms 5 and 6, A and B each independently represent H 2 R 25 represents pyridyl, pyridyl N-oxide, N-methyl-piperidinyl or phenyl; 4 8 N/R 48 N R R48 represents H or alkyl; and Z represents O.
227. 270. The method of claim 269, wherein R' is Cl or H; and R 2 is H, CR or Br. R' and R 2 are independently selected from H, halo, CF3, lower alkyl or benzotriazol-1-
228. 271. The method of claim 269, wherein R is C
229. 272. The methoud of claim 269, and wherein R represents phenyl, 2-pyridyl, 3-pyridyl, 4- pyridyl, 2-pyridyl N-oxide, 3-pyridyl N-oxide, or 4-pyridyl N-oxide. a in ent represent 1-12; R 25 represents pyridyl, pyridyl N-oxide, N-methyl-piperidinyl or phenyl; R 48 represents H or alkyl; and Z represents 0. 270. The method of claim 269, wherein R1 is CI or H; and R 2 is H, CI or Br. 271. The method of claim 269, wherein R 3 is Cl. 272. The method of claim 269, wherein R 25 represents phenyl, 2-pyridyl, 3-pyridyl, 4- pyridyl, 2-pyridyl N-oxide, 3-pyridyl N-oxide, or 4-pyridyl N-oxide. 8 273. The method of claim 269, wherein R 48 represents H or methyl. o 274. The method of claim 269, wherein R 25 represents phenyl, 2-pyridyl, 3-pyridyl, 4- 00 pyridyl, 2-pyridyl N-oxide, 3-pyridyl N-oxide, or 4-pyridyl N-oxide; and R 48 represents H or methyl.
230. 275. The method of claim 269, wherein R' is Cl or H; R 2 is Br, CI, or I; R 3 and R 4 independently represent H or halo; R 25 represents phenyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, 2- C pyridyl N-oxide, 3-pyridyl N-oxide, or 4-pyridyl N-oxide; and R 48 represents H or methyl. S
231. 276. The method of claim 275, wherein R 3 is Cl at the C-8 position and R 4 is H.
232. 277. The method of claim 269, wherein the compound is a compound shown in Figure 16.
233. 278. The method of claim 269, wherein the compound is a compound shown in Figure 17.
234. 279. The method of claim 242, wherein the compound is a compound shown in Figure 18.
235. 280. The method of claim 242, wherein the compound is of the formula: 397 0A B 00 02N_4 R 1 Z or H R 3 is Cl; R e3 IV the dotted line between carbon atoms 5 and 6 represents an optional double bond, such that when a double bond is present, A and B independently represent H, and when no double bond is present between carbon atoms 5 and 6, A and B each independently represent H 2 and R6565 66 66 Z or R 65 represents H or OR 66 wherein R 66 represents alkyl.
236. 281. The method of claim 280, wherein the compound is selected from:
237. 282. A method of treating a synucleinopathic subject, the method comprising, administering to a synucleinopathic subject a farnesyl transferase inhibitor compound of Figure 19, or a stereoisomeric form, or a pharmaceutically acceptable acid or base addition salt form thereof, in a therapeutically effective amount.
238. 283. A method of treating a synucleinopathic subject, the method comprising, administering to a synucleinopathic subject a farnesyl transferase inhibitor compound of Figure or a stereoisomeric form, or a pharmaceutically acceptable acid or base addition salt form thereof, in a therapeutically effective amount. 399 O O
239. 284. The method of claim 283, wherein the compound is selected from the group O consisting of: 00 C1 Br N Br 0 N N NH2 racemic 0 Br r 0 N NH 2 (+)-enantiomer, or 400 Br H Br N N NH 2 O) C
240. 285. A method of treating a synucleinopathic subject, the method comprising, administering to a synucleinopathic subject a therapeutically effective amount of a stereoisomeric form, or a pharmaceutically acceptable acid or base addition salt form of a famesyl transferase inhibitor compound of the formula: Br B N N N NH2
241. 286. A method of treating a synucleinopathic subject, the method comprising, administering to a synucleinopathic subject a therapeutically effective amount of a stereoisomeric form, or a pharmaceutically acceptable acid or base addition salt form of a farnesyl transferase inhibitor compound of the formula: -NH 2 (+)-enantiomer
242. 287. A method of treating a synucleinopathic subject, the method comprising, administering to a synucleinopathic subject a therapeutically effective amount of a stereoisomeric form, or a pharmaceutically acceptable acid or base addition salt form of a farnesyl transferase inhibitor compound of the formula: 'NH 2
243. 288. The method of any of the preceding claims, wherein the synucleinopathic subject has a synucleinopathy selected from the group consisting of: Parkinson's disease, diffuse Lewy body disease, and multiple system atrophy disorder. 402 ID
244. 289. The method of claim 288, wherein the subject is a human. O 290. The method of claim 289, wherein the effective amount comprises about 00 1Ong/kg of body weight to about 1000mg/kg of body weight at a frequency of administration from once a day to once a month. \O 291. The method of claim 290, further comprising administering to the subject an S amount of one or more non-farnesyl transferase inhibitor compounds effective to treat a I neurological disorder. S
245. 292. The method of claim 291, wherein each non-farnesyl transferase inhibitor compound is selected from the group consisting of: dopamine agonist, DOPA decarboxylase inhibitor, dopamine precursor, monoamine oxidase blocker, cathechol 0-methyl transferase inhibitor, anticholinergic, and NMDA antagonist.
246. 293. The method of claim 291, wherein each non-farnesyl trasferase inhibitor compound is selected from the group consisting of Memantine, Aricept, and other acetylcholinesterase inhibitors.
247. 294. An article of manufacture comprising packaging material and a farnesyl transferase inhibitor compound of any of the previous claims, wherein the article of manufacture further comprises a label or package insert indicating that the farnesyl transferase inhibitor compound can be administered to a subject for treating a synucleinopathy.
248. 295. The article of manufacture of claim 294, wherein the synucleinopathy is selected from the group consisting of: Parkinson's disease, diffuse Lewy body disease, and multiple system atrophy disorder.
249. 296. The article of manufacture of claim 294, further comprising one or more non- farnesyl transferase inhibitor compounds effective to treat a neurological disorder.
250. 297. The article of manufacture of claim 294, wherein each non-farnesyl transferase inhibitor compound is selected from the group consisting of: dopamine agonist, DOPA decarboxylase inhibitor, dopamine precursor, monoamine oxidase blocker, cathechol 0-methyl S transferase inhibitor, anticholinergic, and NMDA antagonist. C) O 00 298. A method of treating a synucleinopathic subject, the method comprising, administering to a synucleinopathic subject a farnesyl transferase inhibitor compound of the formula: NO 0 R2 R3 (R 8 )r (RI) R 3 V- A (CR1a2)nA2(CR1a) W (CR 1 b 2 )p t x Y 1 X R4 or a stereoisomeric form, or a pharmaceutically acceptable acid or base addition salt form thereof, in a therapeutically effective amount, wherein: Ria and Rlb are independently selected from: a) hydrogen, b) aryl, heterocycle, C 3 -CIO cycloalkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, R'o R" S(O)m R'O C(O)NRo (R' 0 2 CN, NO 2 (R' 0 2 N-C(NR'IO)-, R'IO R'IO N 3 N(R'0)2, or R" OC(O)NR'O c) unsubstituted or substituted C, -C 6 alkyl wherein the substitutent on the substituted C, C 6 alkyl is selected from unsubstituted or substituted aryl, heterocyclic, C 3 -CIO cycloalkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, R 0 R" S(O)m R'o C(O)NR'O (R' 0 2 N-C(O) CN, (RIO)2 R'o R'Io N 3 and R" OC(O)-NR' 0 R 2 and R 3 are independently selected from: H; unsubstituted or substituted C 1 s 8 alkyl, unsubstituted or substituted C2- 8 alkenyl, unsubstituted or substituted C2-8 alkynyl, NR 6 R 7 unsubstituted or substituted aryl, unsubstituted or substituted heterocycle, O or 6 wherein the substituted group is substituted with one or more of: 1) aryl or heterocyci, unsubstituted or substituted with: a) C 14 alkyl, b) (CH,)p OR', c) NR' R', d) halogen, e) CN, 2) C 3 6 cycloalkyl, 3) OR 6 6a a 6 4) SR S(O)R a, SO 2 R~a -NR R' .NR 6 R 7 NR 6 NR 6 R 7 6 11) -S0 2 -NR 6 R 7 1D O R6 12) S02-R 6 a O R 6 00 n 13) 0 SOR 6 s 14) O O 15) N 3 or 16) F; or R 2 and R 3 are attached to the same C atom and are combined to form -(CH 2 )u wherein one of the carbon atoms is optionally replaced by a moiety selected from: 0, S(O)m, and N(COR'O)-; R 4 and R 5 are independently selected from H and CH 3 and any two of R 2 R 3 R 4 and R 5 are optionally attached to the same carbon atom; R 6 R 7 and R 7 a are independently selected from: H; C 4 alkyl, C 3 6 cycloalkyl, heterocycle, aryl, aroyl, heteroaroyl, arylsulfonyl, heteroarylsulfonyl, unsubstituted or substituted with: a) C-4 alkoxy, b) aryl or heterocycle, c) halogen, d) HO, Y R e) 0 f) SO 2 or g) N(RO)2 or R 6 and R 7 may be joined in a ring; R 7 and R 7 a may be joined in a ring; R 6a is selected from: CI4 alkyl, C3- 6 cycloalkyl, heterocycle, aryl, unsubstituted or substituted with: a) Cl4 alkoxy, b) aryl or heterocycle, c) halogen, d) HO, C.) 00 e) 0 f--SO 2 or 5 g) N(R 0)2; R 8 is independently selected from: IND a) hydrogen, b) aryl, heterocycle, C 3 -CIO cycloalkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, perfluoroalkyl, F, Cl, Br, R' 0 R" S(O),m R' 0 C(O)NR' 0 (R" 0 2 R" 0 2 N-C(NR' 0 CN, NO 2 R' 0 R' 0 N 3 N(R' 0 2 or R" OC(O)NR' 0 and c) CI -C 6 alkyl unsubstituted or substituted by aryl, cyanophenyl, heterocycle, C 3 -CIO cycloalkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, perfluoroalkyl, F, Cl, Br, R" 0 R" S(O)m, R' 0 (R' 0 2 R' 0 2 N-C(NR' 0 CN, R' 0 R' 0 N 3 -NR),or R' 0 R 9 is selected from: a) hydrogen, b) C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, perfluoroalkyl, F, Cl, Br, R" 0 S(O)m' R C(O)NR' 0 (R" 0 2 R" 0 2 N-C(NR' 0 CN, NO 2 R' 0 R" 0 N 3 NR"2,or R" OC(O)NR' 0 and C) C I -C 6 alkyl unsubstituted or substituted by perfluoroalkyl, F, Cl, Br, R1 0 R"1 S(O),m R' 0 C(O)NR' 0 (R' 0 2 R' 0 2 N-C(NR' 0 CN, R" 0 R' 0 N 3 N(R' 0 2 or OC(O)NR' 0 R1 0 is independently selected from hydrogen, C, -C 6 alkyl, benzyl and aryl; R" is independently selected from C, -C 6 alkyl and aryl; A' and A 2 are independently selected from: a bond, CH=CH--, C.tbd.C--, C(O)NR' 0 NR' 0 0, N(R' 0 -S(0) 2 N(R' 0 N(R' 0 )S(O) 2 or S(O)m V is selected from: a) hydrogen, b) heterocycle, c) aryl, 407 ID Sd) C, -C 2 0 alkyl wherein from 0 to 4 carbon atoms are replaced with a heteroatom selected from O, S, and N, and O e) C 2 -C 20 alkenyl, 00 provided that V is not hydrogen if A' is S(O)m and V is not hydrogen if A' is a bond, n is 0 and A 2 is S(O)m; W is a heterocycle; SX is CH 2 or S(=0)m Y is unsubstituted or substituted aryl or unsubstituted or substituted heterocycle, ("1 I wherein the substituted aryl or substituted heterocycle is substituted with one or more S 10 of: 1) CI-4 alkyl, unsubstituted or substituted with: a) Ci-4 alkoxy, b) NR 6 R 7 c) C3- 6 cycloalkyl, d) aryl or heterocycle, e) HO, f) S(O)m R 6 a, or g) C(O)NR 6 R 7 2) aryl or heterocycle, 3) halogen, 4) OR 6 NR 6 R 7 6) CN, 7) NO 2 8) CF3 9) R 6a -C(O)NR 6 R 7 or 11) C 3 -C 6 cycloalkyl m is 0, 1 or 2; n is 0, 1,2, 3 or 4; pisO, 1,2, 3 or4; q is 1 or 2; r is 0 to 5, provided that r is 0 when V is hydrogen; s is 0 or 1; ID St is 0 or 1; and u is 4 or C.) 0 OO 299. method of treating a synucleinopathic subject, the method comprising, administering to a synucleinopathic subject a farnesyl transferase inhibitor compound of the formula: G C (R 8 )r (R 9 N D R2 V- A(CR 2)n A CR a2)n W -(CR 1 2)p N N- Z t j R4" or a stereoisomeric form, or a pharmaceutically acceptable acid or base addition salt form thereof, in a therapeutically effective amount, wherein: R la and R'b are independently selected from: a) hydrogen, b) aryl, heterocycle, C 3 -Clo cycloalkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, R 0 R" S(O)m R'O C(O)NR'° CN(R' 0 2 R' 0 2 CN, NO 2 RI 0 R I o N 3 N(R' 0 2 or R" OC(O)NRo c) unsubstituted or substituted CI -C 6 alkyl wherein the substitutent on the substituted CI C 6 alkyl is selected from unsubstituted or substituted aryl, heterocyclic, C 3 -Clo cycloalkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, R' 0 R" S(O)m R I 0 C(O)NR'O (RI') 2 R' 2 N-C(NRi 0 CN, R' i R 1 i N 3 N(R' 0 2 and R" OC(O)--NR 0 R 2 and R 3 are independently selected from: H; unsubstituted or substituted Ci.g alkyl, unsubstituted or substituted C 2 8 alkenyl, unsubstituted or substituted C2- 8 alkynyl, unsubstituted or substituted aryl, unsubstituted or substituted heterocycle, 409 OR' or 0 wherein the substituted group is substituted with one or more of: 1) aryl or heterocycle, unsubstituted or substituted with: a) C 1 alkyl, b) OR', c) (CH,)p NR' R', d) halogen, e) CN, 2) C 3 6 cycloalkyl, 6 3) OR, 4) SR 6 S(O)R a, SO 2 R~a -NR 6 R' N.. R6 NR 6 R 7 NR 6 NR 6 R 7 b 11) -S0 2 -NR 6 R 7 ID O R 6 12) N-S02-R 6a 0 R 6 00 I 13) o OOR 6 S 1 4) o O N 3 or 5 16) F; or R 2 and R 3 are attached to the same C atom and are combined to form (CH 2 )u wherein one of the carbon atoms is optionally replaced by a moiety selected from: O, S(O)m, NC(O)-, and -N(CORi 0 R 4 is selected from H and CH 3 and any two of R 2 R 3 and R 4 are optionally attached to the same carbon atom; R 6 R 7 and R 7a are independently selected from: H; C-4 alkyl, C 3 6 cycloalkyl, heterocycle, aryl, aroyl, heteroaroyl, arylsulfonyl, heteroarylsulfonyl, unsubstituted or substituted with: a) Ci-4 alkoxy, b) aryl or heterocycle, c) halogen, d) HO, R"1 e) 0 f) SO 2 R, or g) N(RI) 2 or R 6 and R 7 may be joined in a ring; R 7 and R 7a may be joined in a ring; R 6a is selected from: CI4 alkyl, C 3 6 cycloalkyl, heterocycle, aryl, unsubstituted or substituted with: a) CI- 4 alkoxy, b) aryl or heterocycle, c) halogen, d) HO, 00 e) 0 f-SO 2 ,or R 8 is independently selected from: a) hydrogen, IND b) aryl, heterocycle, C 3 -CIO cycloalkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, perfluoroalkyl, F, Cl, Br, R' R" S(O),m R' 0 C(O)NR 10 (R' 0 2 R' 0 2 N-C(NR' 0 CN, NO 2 R' 0 R' 0 N 3 N(R' 0 2 or OC(O)NR' 0 and C) CI -C 6 alkyl unsubstituted or substituted by aryl, cyanophenyl, heterocycle, C 3 -C 10 cycloalkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, perfluoroalkyl, F, CI, Br, R1 0 R" S(O)m R' 0 C(O)NH-, (R 10)2 R' 0 2 N-C(NR' 0 CN, R' 0 R' 0 N 3 NR),or R" 0 C(O)NH-; R 9 is selected from: a) hydrogen, b) alkenyl, alkynyl, perfluoroalkyl, F, Cl, Br, R' 0 R' S(O)m RIO C(O)NR" 0 (R' 0 2 R' 0 2 N-C(NR' 0 CN, NO 2 R" R' 0 N 3 N(R' 0 2 or R" OC(O)NR' 0 and C) C, -C 6 alkyl unsubstituted or substituted by perfluoroalkyl, F, Cl, Br, R1 0 R 1 1 S(O)m R" 0 C(O)NR' 0 (R' 0 2 R' 0 2 N-C(NR' 0 CN, R" 0 R' 0 N 3 N(R' 0 2 or OC(O)NR' 0 R1 0 is independently selected from hydrogen, C, -C 6 alkyl, benzyl and aryl; R"1 is independently selected from CI -C 6 alkyl and aryl; A'I and A 2 are independently selected from: a bond, CH=CH--, C.tbd.C--, C(O)NR' 0 NR" 0 0, N(R' 0 S(0) 2 N(R' 0 N(R' 0 )S(O) 2 or S(O)m G is H 2 or 0; V is selected from: a) hydrogen, b) heterocycle, c) aryl, ID d) Ci -C 20 alkyl wherein from 0 to 4 carbon atoms are replaced with a a heteroatoin selected from O, S, and N, and O e) C 2 -C 20 alkenyl, 00 provided that V is not hydrogen if A' is S(O)m and V is not hydrogen ifA' is a bond, n is 0 and A 2 is S(O)m W is a heterocycle; O-X is CH 2 or S(=O)m Z is a unsubstituted or substituted group selected from aryl, heteroaryl, arylmethyl, I\ heteroarylmethyl, arylsulfonyl, heteroarylsulfonyl, wherein the substituted group is 0 10 substituted with one or more of the following: 1) C-4 alkyl, unsubstituted or substituted with: a) C-4 alkoxy, b) NR 6 R 7 c) C 3 6 cycloalkyl, d) aryl or heterocycle, e) HO, f) S(O)m R 6 a, or g) C(O)NR 6 R 7 2) aryl or heterocycle, 3) halogen, 4) OR 6 NR 6 R 7 6) CN, 7) NO 2 8) CF3 9) S(O)m R 6a C(O)NR 6 R 7 or 11) C 3 -C 6 cycloalkyl; mis 0, 1 or 2; n is 0, 1,2, 3 or 4; pis0, 1,2, 3 or 4; q is 1 or 2; r is 0 to 5, provided that r is 0 when V is hydrogen; s is 0 or 1; ID St is 0 or 1; and u is 4or C) 00 300. A method of treating a synucleinopathic subject, the method comprising, administering to a synucleinopathic subject a farnesyl transferase inhibitor compound of the formula: R 8 R 2 R 3 c (R (R 9 A(CR a 2 2 (CRa) W (CR 1 b 2 p N N- Z 0 t x O1 R4 s G or a stereoisomeric form, or a pharmaceutically acceptable acid or base addition salt form thereof, in a therapeutically effective amount, wherein: R la and Rlb are independently selected from: a) hydrogen, b) aryl, heterocycle, C 3 -Clo cycloalkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, R 0 R" S(O)m R' C(O)NRo 1 (R'I) 2 RI 0 2 N-C(NRIo)--, CN, NO 2 R' 0 R 0 N 3 N(RI') 2 or R" OC(O)NR c) unsubstituted or substituted CI -C 6 alkyl wherein the substitutent on the substituted Ci C 6 alkyl is selected from unsubstituted or substituted aryl, heterocyclic, C 3 -Clo cycloalkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, R 1 0 R" S(O)m R 1 0 C(O)NR' i (R'I) 2 R 10 2 N-C(NRi 0 CN, R i 0 R 10 N 3 2 and R" OC(O)--NR 0 R 2 and R 3 are independently selected from: H; unsubstituted or substituted CI-8 alkyl, unsubstituted or substituted C2-8 alkenyl, unsubstituted or substituted C 2 8 alkynyl, unsubstituted or substituted aryl, unsubstituted or substituted heterocycle, 414 Y OR' C) or 0 wherein the substituted group is substituted with one or more of: 1) aryl or 00 heterocycle, unsubstituted or substituted with: a) CI-4alkyl, b) (CH,)p OR', c) (CH,)p NR' R', d) halogen, e) CN, 2) C 3 6 cycloalkyl, 6 3) OR, 4) SR 6 a, S(O)R~a, SO 2 R R 6 a, -NR R', 6)6 7) 0 OR6 6 R 8) 0 0 y NR 6 R 9) 0 .NR 6 R 7 0 11) -S0 2 -NR 6 R 7 IO 12) N- SO 2 -Rea O R 6 12) S2-R 6 8 OR6 00 13) 0 OR 6 S 14) o N 3 or 16)F;or R 2 and R 3 are attached to the same C atom and are combined to form (CH 2 )u wherein one of the carbon atoms is optionally replaced by a moiety selected from: O, S(O)m, and N(CORi)-; R 4 is selected from H and CH 3 and any two of R 2 R 3 and R 4 are optionally attached to the same carbon atom; R 6 R 7 and R 7 a are independently selected from: H; C-4 alkyl, C 3 6 cycloalkyl, heterocycle, aryl, aroyl, heteroaroyl, arylsulfonyl, heteroarylsulfonyl, unsubstituted or substituted with: a) C-4 alkoxy, b) aryl or heterocycle, c) halogen, d) HO, YR" e) 0 f) SO 2 R 1 or g) N(R' 0 2 or R 6 and R 7 may be joined in a ring; R 7 and R 7 a may be joined in a ring; R 6 is selected from: Cl- 4 alkyl, C 3 6 cycloalkyl, heterocycle, aryl, unsubstituted or substituted with: a) C- 4 alkoxy, b) aryl or heterocycle, c) halogen, d) HO, Y R 1 1 0e) 0 00 f) SO 2 or g) N(R 2 R 8 is independently selected from: a) hydrogen, b) aryl, heterocycle, C 3 -CIO cycloalkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, perfluoroalkyl, F, Cl, Br, R' 0 R' 1 S(O)m, R' 0 C(O)NR' 0 (R' 0 2 R" 0 2 N-C(NR' 0 CN, NO 2 R" 0 R" 0 N 3 N(R' 0 2 or R" OC(O)NR' 0 and C) C I -C 6 alkyl unsubstituted or substituted by aryl, cyanophenyl, heterocycle, C 3 -C 1 0 cycloalkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, perfluoroalkyl, F, Cl, Br, Rio R' S(O)m R' 0 (R" 0 2 R' 0 2 N-C(NR' 0 CN, R' 0 R" 0 N 3 R' 0 OC(O)NH--; R 9 isselected from: a) hydrogen, b) C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, perfluoroalkyl, F, Cl, Br, R' 0 R' S(O)m R' 0 C(O)NR' 0 (R' 0 2 R' 0 2 N-C(NR' 0 CN, NO 2 R" 0 R" 0 N 3 R" OC(O)NR' 0 and C) CI -C 6 alkyl unsubstituted or substituted by perfluoroalkyl, F, Cl, Br, R" 0 S(O)m' ,R' 0 C(O)NR' 0 (R' 0 2 R" 0 2 N-C(NR' 0 CN, R" 0 RIO N 3 N(R' 0 2 or R" OC(O)NR' 0 R1 0 is independently selected from hydrogen, C, -C 6 alkyl, benzyl and aryl; R"1 is independently selected from C I -C 6 alkyl and aryl; A] and A 2are independently selected from: a bond, CH=CH--, C.tbd.C--, C(O)NR' 0 NR' 0 0, N(R1 0 S(0) 2 N(R' 0 N(R' 0 )S(O) 2 or S(O),m; G isO0; V is selected from: a) hydrogen, b) heterocycle, c) aryl, 417 ID d) Ci -C 20 alkyl wherein from 0 to 4 carbon atoms are replaced with a a heteroatom selected from O, S, and N, and O e) C 2 -C 2 0 alkenyl, 00 provided that V is not hydrogen if A' is S(O)m and V is not hydrogen if A' is a bond, n is 0 and A 2 is S(O)m W is a heterocycle; X is CH 2 or Z is a unsubstituted or substituted group selected from aryl, heteroaryl, arylmethyl, ("1 IN heteroarylmethyl, arylsulfonyl, heteroarylsulfonyl, wherein the substituted group is O 0 10 substituted with one or more of the following: 1) C-4 alkyl, unsubstituted or substituted with: a) Ci- 4 alkoxy, b) NR 6 R 7 c) C3- 6 cycloalkyl, d) aryl or heterocycle, e) HO, f) S(O) R 6 a, or g) C(O)NR 6 R 7 2) aryl or heterocycle, 3) halogen, 4) OR 6 NR 6 R 7 6) CN, 7) NO 2 8) CF 3 9) S(O)m R 6a C(O)NR 6 R 7 or 11) C 3 -C 6 cycloalkyl; m is 0, 1 or 2; n is 0, 1,2, 3 or 4; pis0, 1, 2, 3 or4; q is 1 or 2; r is 0 to 5, provided that r is 0 when V is hydrogen; s is 1; 418 t is 0 or 1; and u is 4 or O 0 00 301. The method of claim 298, wherein the compound is of the formula: (R (R 9 )R 2 R3 SI O SV- A(CRa 2 )nA 2 (CRa 2 W- (CR 1 b 2 p R4 or a stereoisomeric form, or a pharmaceutically acceptable acid or base addition salt form thereof, in a therapeutically effective amount, wherein: Rla is independently selected from: hydrogen or C, -C 6 alkyl; R' b is independently selected from: a) hydrogen, b) aryl, heterocycle, cycloalkyl, R' 1 -N(R' 0 2 or C 2 -C 6 alkenyl, c) unsubstituted or substituted Ci -C 6 alkyl wherein the substitutent on the substituted Ci C 6 alkyl is selected from unsubstituted or substituted aryl, heterocycle, cycloalkyl, alkenyl, R' 0 and N(R 10 )2 R 3 R 4 and R 5 are independently selected from H and CH3; NR 6 R 7 R is H; O or Cl-5 alkyl, unbranched or branched, unsubstituted or substituted with one or more of: 1) aryl, 2) heterocycle, 3) OR 6 4) SR 6 a, SO2 R 6 or Y NR 6 R 7 0 00 and any two of R 2 R 3 R 4 and R 5 are optionally attached to the same carbon atom; R 6 R 7 and R 7'are independently selected from: H; C14 alkyl, C 3 6 cycloalkyl, aryl, heterocycle, unsubstituted or substituted with: a) C1 4 alkoxy, b) halogen, or IND c) aryl or heterocycle; R 6 a is selected from: C14 alkyl or C 3 6 cycloalkyl, unsubstituted or substituted with: a) C14alkoxy, b) halogen, or c) aryl or heterocycle; R' is independently selected from: a) hydrogen, b) C, -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C, -C 6 perfluoroalkyl, F, Cl, R" 0 R" 0 C(O)NR' 0 CN, N0 2 (R' 0 2 N-C(NR 1 R 10 R' 0 N(R 0 2 or R OC(O)NR' 0 and C) C, -C 6 alkyl substituted by C, -C 6 perfluoroalkyl, R" 0 R' 0 C(O)NR' 0 (R' 0 2 N- C(NR' 0 R" 0 R' 0 N(R' 0 2 or R" OC(O)NR' 0 R 9 is selected from: a) hydrogen, b) C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C, -C 6 perfluoroalkyl, F, Cl, R" 0 RI S(O)m -,R1 C(O)NR' 0 CN, NO 2 (R' 0 2 N-C(NR' 0 R' 0 R' 0 N(R' 0 2 or R OC(O)NR' 0 and C) CI -C 6 alkyl unsubstituted or substituted by C, -C 6 perfluoroalkyl, F, CI, R' 0 RI S(O)m R' 0 C(O)NR' 0 CN, (R' 0 2 N-C(NR' 0 R' 0 R' 0 N(R' 0 2 or R''OC(O)NR" R1 0 is independently selected from hydrogen, C, -C 6 alkyl, benzyl and aryl; R"1 is independently selected from CI -C 6 alkyl and aryl; A' and A 2 are independently selected from: a bond, CH=CH--, C.tbd.C--, C(O)NR' 0 0, N(Rl 0 or S(O)m ID V is selected from: a) hydrogen, O b) heterocycle selected from pyrrolidinyl, imidazolyl, pyridinyl, thiazolyl, pyridonyl, 2- 00 oxopiperidinyl, indolyl, quinolinyl, isoquinolinyl, and thienyl, c) aryl, d) Ci -C 20 alkyl wherein from 0 to 4 carbon atoms are replaced with a a heteroatom selected \O from O, S, and N, and Se) C 2 -C 20 alkenyl, and ND provided that V is not hydrogen if A' is S(O)m and V is not hydrogen if A' is a bond, n is 0 O O 10 and A 2 is S(O) W is a heterocycle selected from pyrrolidinyl, imidazolyl, pyridinyl, thiazolyl, pyridonyl, 2- oxopiperidinyl, indolyl, quinolinyl, or isoquinolinyl; X is CH 2 or Y is mono- or bicyclic aryl, or mono- or bicyclic heterocycle, unsubstituted or substituted with one or more of: a) Ci. 4 alkyl, b) C-4 alkoxy, c) halogen, or d) NR 6 R m is 0, 1 or 2; n is 0, 1,2, 3 or 4; p is0, 1,2, 3 or 4; r is 0 to 5, provided that r is 0 when V is hydrogen; s is 0 or 1; and t is 0 or 1.
251. 302. The method of claim 299, wherein the compound is of the formula: 2G (R8)r (R 9 R IV---AI(CR a2)A2(CR CR b;n -N N- Z I O O C)D 0 01 -q- 421 or a stereoisomeric form, or a pharmaceutically acceptable acid or base addition salt form thereof, in a therapeutically effective amount, 5 wherein: Ria is independently selected from: hydrogen or C 1 -C 6 alkyl; Rlb is independently selected from: a) hydrogen, b) aryl, heterocycle, cycloalkyl, R' 1 N(R' 0 2 or C 2 -C 6 alkenyl, 0 c) unsubstituted or substituted C, -C 6 alkyl wherein the substitutent on the substituted Ci C 6 alkyl is selected from unsubstituted or substituted aryl, heterocycle, cycloalkyl, alkenyl, R 1 i and N(R') 2 R 3 and R 4 are independently selected from H and CH 3 NR 6 R 7 R is H; O or Ci-5 alkyl, unbranched or branched, unsubstituted or substituteci with one or more of: 1 aryl, 2) heterocycle, 3) OR 6 4) SR 6 a, SO 2 R 6 a, or f o 5) 0 and any two of R 2 R 3 R 4 and R 5 are optionally attached to the same carbon atom; R 6 R 7 and R 7 a are independently selected from: H; C14 alkyl, C 3 6 cycloalkyl, aryl, heterocycle, unsubstituted or substituted with: a) C 1 4 alkoxy, b) halogen, or c) aryl or heterocycle; R 6a is selected from: Cl- 4 alkyl or C 3 6 cycloalkyl, unsubstituted or substituted with: a) C-4 alkoxy, IND 422 b) halogen, or c) aryl or heterocycle; oR 8is independently selected from: 00 a) hydrogen, b) C, -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C, -C 6 perfluoroalkyl, F, Cl, RIO RIO C(O)NR' 0 CN, NO 2 (R' 0 2 N-C(NR' 0 RIO RIO N(R' 0 2 orR' OC(O)NR' 0 and C) CI -C 6 alkyl substituted by CI -C 6 perfluoroalkyl, RIO RIO C(O)NR' 0 (R' 0 2 N- C(NR' 0 RI RIO N(R' 0 2 or R" OC(O)NR' 0 R 9 is selected from: a) hydrogen, b) C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C, -C 6 perfluoroalkyl, F, Cl, RIO R" S(O)m 1 C(O)NR' 0 CN, NO 2 (R' 0 2 N-C(NR' 0 RIO RIO N(R' 0 2 or R OC(O)NR' 0 and C) C, -C 6 alkyl unsubstituted or substituted by C, -C 6 perfluoroalkyl, F, CI, RIO R' S(O)m RIO C(O)NR' 0 CN, (R' 0 2 N-C(NR' 0 RIO RIO N(R' 0 2 or R" OC(O)NR' 0 RIO is independently selected from hydrogen, C 1 -C 6 alkyl, benzyl and aryl; R" is independently selected from C, -C 6 alkyl and aryl; A' and A 2 are independently selected from: a bond, CH=CH--, C.tbd.C--, C(O)NR' 0 0, N(Rl 0 or S(O)m; V is selected from: a) hydrogen, b) heterocycle selected from pyirolidinyl, imidazolyl, pyridinyl, thiazolyl, pyridonyl, 2- oxopiperidinyl, indolyl, quinolinyl, isoquinolinyl, and thienyl, c) aryl, d) C, -C 2 0 alkyl wherein from 0 to 4 carbon atoms are replaced with a a heteroatom selected from 0, S, and N, and e) C 2 -C 20 alkenyl, and provided that V is not hydrogen if A' is and V is not hydrogen if A' is a bond, n isO0 and A 2 is S(O)m; G is H 2 orO0; W is a heterocycle selected from pyrrolidinyl, imidazolyl, pyridinyl, thiazolyl, pyridonyl, 2- oxopiperidinyl, indolyl, quinolinyl, or isoquinolinyl; X is CH 2 or 423 Z is mono- or bicyclic aryl, mono- or bicyclic heteroaryl, mono- or bicyclic arylmethyl, mono- or bicyclic heteroarylmethyl, mono- or bicyclic arylsulfonyl, mono- or bicyclic C.) 00 1) C14 alkyl, unsubstituted or substituted with: a) C14 alkoxy, b) NR' R', C) C 3 6 cycloalkyl, d) aryl or heterocycle. IND e) HO, g) C(O)NR 6 R', 2) aryl or heterocycle, 3) halogen, 4) OR 6 5) NR 6 R', 6) CN, 7) NO 2 8) CF 3 9) S(O),m R 6 7 10) C(O)NR R ,or 11) C 3 -C 6 cycloalkyl; m is 0, 1 or 2; n isO0, 1, 2, 3 or 4; p isO0, 1, 2, 3or 4; r is 0 to 5, provided that r is 0 when V is hydrogen; s isO0 or 1; t is Oor 1; and u is 4 or provided that when G is H 2 and W is imidazolyl, then the substitutent (CRla 2 )n A 2(CR 2 is not Hand provided that when X is or then t is I and the substitutent A' (CR]a 2 )n A 2 (CRla 2 )n is not H. 424
252. 303. A method of treating a syriucleinopathic subject, the method comprising, __administering to a synucleinopathic subject a farnesyl transferase inhibitor compound selected from the list consisting of: 00 2(S)-Butyl-l1-(2,3-diaminoprop- l-yl)-4-(l -naphthoyl)piperazine 1 -(3-Amino-2-(2-naphthylmethylamino)prop- 1-yI)-2(S)-butyi-4-( 1-naphthoyI)piperazine 2(S)-Butyl- 1- 1-(2-naphthylmethyl)]-4,5-dihydroimidazol }methyl-4-( 1- naphthoyl)piperazine 1 -Benzylimidazol)methyl]-2(S)-butyl-4-( 1 -naphthoyl)piperazine IN1 1-(4-NitrobenzyI)imidazolyl]methyl -2(S)-butyl-4-( I -naphthoyi)piperazine 1 -(3-Acetamidomethylthio-2(R)-aminoprop- 1 -yI)-2(S)-butyl-4-( 1 -naphthoyl)piperazine 2()Btl iiaoyNtylsloyi-l-aptolpprzn 2(S)-Butyl- 1 -2--imidazolylethyl4sulfoy- -naphthoyl)piperazine 2(S)-Butyl-4-( 1 -naphthoyl)- I -(3-pyridylmethyl)piperazine 1 -2(S)-butyl-(2(R)-(4-nitrobenzyi)amino-3 -hydroxypropyi)-4-( I -naphthoyl)piperazine 1 -(2(R)-Amino-3-hydroxyheptadecyl)-2(S)-butyl-4-( 1 -naphthoyl)piperazine 2(S)-Benzyl- 1 -imidazolyl-4-methyl-4-( 1 -naphthoyl)piperazine 1 -(2(R)-Amino-3-(3-benzylthio)propyl)-2(S)-butyl-4-(1 -naphthoyl)piperazine 1 -(2(R)-Amino-3- [3 -(4-nitrobenzylthio)propyl] I -naphthoyl)piperazine 2(S)-Butyl- 1 -[(4-imidazolyl)ethyl]-4-( 1 -naphthoyl)piperazine 2(S)-Butyl- 1 -I(4-imidazolyl)methyl]-4-( 1 -naphthoyl)piperazine 2(S)-Butyl- 1 -naphth-2-ylmethyl)- I H-imidazol-5-yl)acetyl]-4-( 1 -naphthoyl)piperazine 2(S)-Butyl- 1 -naphth-2-ylmethyl)- 1 H-imidazol-5-yl)ethyl]-4-( 1 -naphthoyl)piperazine 1 -(2(R)-Amino-3-hydroypropyl)-2(S)-butyl-4-( 1 -naphthoyl)piperazine 1 -(2(R)-Amino-4-hydroxybutyl)-2(S)-butyl-4-( 1 -naphthoyl)piperazi ne 1 -(2-Amino-3-(2-benzyloxyphenyl)propyl)-2(S)-butyl-4-(1 -naphthoyl)piperazine 1 -(2-Amino-3 -(2-hydroxyphenyl)propyl)-2(S)-butyl-4-( 1 -naphthoyl)piperazine 1 -[3-(4-imidazolyl)propyl]-2(S)-butyl-4-( 1 -naphthoyl)piperazine 2(S)-n-Butyl-4-( I -naphthoyl)- 1 -I 2(S)-n-Butyl-4-( I -naphthoyl)- 1-ri 2(S)-n-Butyl- 1-ri -(4-cyanobenzyl)imidazol-5-ylmethyl]-4-( 1 -naphthoyl)piperazine 2(S)-n-Butyl- 1-ri -(4-methoxybenzyl)imidazol-5-ylmethyl]-4-( I -naphthoyl)piperazine 2(S)-n-Butyl- 1-[I -(3-methyl-2-butenyl)imidazol-5-ylmethyl]-4-( I -naphthoyl)piperazine 2(S)-n-Butyl- 1 -I -(4-fluorobenzyl)imidazol-5-ylmethyl]-4-(1 -naphthoyl)piperazine 2(S)-n-Butyl- 1-[i -(4-chlorobenzyl)imidazol-5-ylmethyl]-4-( I -naphthoyl)piperazine 1IND(-rmbny~mdzo--lehl-()nbtl-- nptolpprzn 1 1 -(4-Bromobenzyl)imidazol-5-ylmethyl]-2(S)-n-butyl-4-( 1 -naphthoyl)piperazine 1- (-rmbny0mdzl5ymty]-()nbtl4( nptolpprzn o 2(S)-n-Butyl-4-( I -naphthoyl)- 1I-[1I 00 piperazine 2(S)-n-Butyl- 1I-[1I -(4-methylbenzyl)imidazol-5-ylmethyl]-4-( 1 -naphthoyl)-piperazine 2(S)-n-Butyl- 1 -[1I -(3-methylbenzyl)imidazol-5-ylmethyl]-4-( I -naphthoyl)-piperazine 1 1 -(4-Phenylbenzyl)imidazol-5-ylmethyl]-2(S)-n-butyl-4-( 1 -naphthoyl)-piperazine 2(S)-n-Butyl-4-( I -naphthoyl)- 1 -I 2(S)-n-Butyl-4-( I -naphthoyl)- I -I C) 10 1- (1 -(4-cyanobenzyl)- 1 H-imidazol-5-yI]acetyl -2(S)-n-butyl-4-( 1 -naphthoyl)piperazine 1 -dimethylphenyl)-4-(4-imidazolylmethyl)-piperazin-2-one 5(S)-n-Butyl-4-[ I-(4-cyanobenzyl)imidazol-5-ylmethyl]- 1 -(2,3-dimethylphenyl)piperazin- 2-one 1-(4-Cyanobenzyl)imidazol-5-ylmethyl]- I -(2,3-dimethylphenyl)-5(S)-(2- methoxyethyl)piperazin-2-one 1 -(3-Chlorophenyl)-4-[ I-(4-cyanobenzyl)-5-imidazolylmethyl]-5-[2- (methanesul fonyl)ethyl]-2-piperazinone 1 -(3-Chlorophenyl)-4-[ 1-(4-cyanobenzyl)-5-imidazolylmethyl]-5-[2- (ethanesul fonyl)ethyl]-2-piperazinone I -(3-Chlorophenyl)-4-[ I-(4-cyanobenzyl)-5-imidazolylmethyl]-5-[2- (ethanesul fonyl)methyl] -2-piperazinone 1 -(3-Chlorophenyl)-4-[ 1-(4-cyanobenzyl)-5-imidazolylmethyl]-5-[N-ethyl-2- acetamido]-2-piperazinone (+)-5-(2-Butynyl)- 1 -chlorophenyl)-4-[ I-(4-cyanobenzyl)-5-imidazolylmethyl]-2- piperazinone 1 -Chlorophenyl) 1-(4-cyanobenzyl)-5 -i midazolIylmethyl ]-2-pi perazi none 5(S)-Butyl-4-[ 1-(4-cyanobenzyl-2-methyl)-5-imidazolylmethyl]- 1 -dimethylphenyl)- piperazin-2-one 1-(2-(4-Cyanophenyl)-2-propyl)-5-imidazolylmethyl]- 1 -chilorophenyl)-5 methylsulfonylethyl)piperazin-2-one 5(S)-n-Butyl-4-[ 1-(4-cyanobenzyl)-5-imidazolylmethyl]- 1 -(2-methylphenyl)piperazin-2- one 1-(4-Cyanobenzyl)-5-imidazolylmethyl]-5(S)-(2-fluoroethyl)- 1 chlorophenyl)piperazin-2-one 4-[3-(4-Cyanobenzyl)pyridin-4-yl]- 1 -chlorophenyl)-5(S)-(2-methylsulfonylethyl)- piperazin-2-one U 4-[5-(4-Cyanobenzyl)- 1 -imidazolyiethyl]- 1 -(3-chlorophenyl)piperazin-2-one 00 or a stereoisomeric form, or a pharmaceutically acceptable acid or base addition salt form thereof, in a therapeutically effective amount.
253. 304. A method of treating a synucleinopathic subject, the method comprising, administering to a synucleinopathic subject a farnesyl transferase inhibitor compound selected from the list consisting of: 1- -(4-Nitrobenzyl)imidazolyljmethyl }-2(S)-butyl-4-( 1-naphthoyl)piperazine 1 1- Benzylimidazol)methyl]-2(S)-butyl-4-( I-naphthoyl)piperazine I -(2(R)-Amino-3 -benzylthio)propyl)-2(S)-butyl-4-( 1-naphthoyl)piperazine 1 -(2(R)-Amino-3-[3-(4-nitrobenzylthio)propyl])-2(S)-butyl-4-( -naphthoyl)piperazine 2(S)-n-Butyl- I J[I -(4-cyanobenzyl)imidazol-5-ylmethyl]-4-( 1 -naphthoyl)piperazine 2(S)-n-Butyl- I -(4-cyanobenzyl)imidazol-5-ylmethyl]-4-(2,3 dimethylphenyl)piperazin- 2(S)-n-Butyl- I-[I -(4-chlorobenzyl)imidazol-5-ylmethyl]-4-( 1 -naphthoyl)piperazine 1- ([1I -(4-Cyanobenzyl)- 1 H-imidazol-5-yl]acetyl -2(S)-n-butyl-4-( 1 -naphthoyl)piperazine 1-[ri -(4-Cyanobenzyl)imidazol-5-ylmethyl]-4-(2,3 -dimethylphenyl)-2(S)-(2- methoxyethylI)piperazi n-5 -one 5(S)-n-Butyl-4-[ 1-(4-cyanobenzy1)-5-imidazolylmethyl]- 1 -(2-methylphenyl)piperazin-2- one 1 -Chlorophenyl)-4-[ 1-(4-cyanobenzyl)-5-imidazolylmethyl]-5-[2- (methanesulfonyl)ethyl] -2-piperazinone 1 -(3-Chlorophenyl)-4-[ I-(4-cyanobetizyl)-5-imidazolylmethyl]-5-[2- (ethanesulfonyl)ethyl] -2-piperazinone 1 -Chilorophenyl)-4- [1I-(4-cyanobenzyl)-5 imi dazolIyl methyl]- 5 (ethanesulfonyl)methyl] -2-piperazinone 1 -(3-Chlorophenyl)-4-[ 1-(4-cyanobenzyl)-5-imidazolyl-methyl]-2-piperazinone or a stereoisomeric form, or a pharmaceutically acceptable acid or base addition salt form thereof, in a therapeutically effective amount. IND 427
254. 305. The method of claim 304, wherein the compound is 1-(3-Chlorophenyl)-4-[1-(4- -2-piperazinone or a stereoisomeric form, or a pharmaceutically acceptable acid or base addition salt form thereof. 00
255. 306. A method of treating a synucleinopathic subject, the method comprising, administering to a synucleinopathic subject a farnesyl transferase inhibitor compound selected from the list consisting of: 1 -di methylphenyl)-4-(4- imidazolylmethyl)-piperazin-2 -one (1 5(S)-n-Butyl-4-[ I-(4-cyanobenzyl)imidazol-5-ylmethyl]- I -(2,3-dimethylphenyl)piperazin- 2-one 1-(4-Cyanobenzyl)imidazol-5-ylmethyl]- 1 -(2,3-dimethylphenyl)-5(S)-(2- (1 methoxyethyl)piperazin-2-one I -(3-Chlorophenyl)-4-[ I-(4-cyanobenzyl)-5-imidazolylmethyl]-5-[2- (methanesulfonyl)ethyl -2-piperazi none I -(3-Chlorophenyl)-4-[ I-(4-cyanobenzyl)-5-imidazolylmethyl]-5-[2- (ethanesulfonyl)ethyl]-2-piperazinone 1 -(3-Chlorophenyl)-4-[ 1-(4-cyanobenzyl)-5-imidazolylmethyl]-5-[2- (ethanesul fonyl)methyl] -2-piperazinone 1 -Ch lorophenyl)-4- [1 -(4-cyanobenzy l)-5-imrnidazolylmethy 11-5 -ethyl -2- acetamni do] -2-piperazi none (±)-5-(2-Butynyl)- 1 -chlorophenyl)-4-[l1-(4-cyanobenzyl)-5-imidazolylmethyl]-2- piperazinone 1 -Chlorophenyl)-4- 1-(4-cyanobenzyl)-5-imidazolylmethyl] -2-piperazi none 5(S)-Butyl-4-[ 1-(4-cyanobenzyl-2-methyl)-5-imidazolylmethyl]- 1 -dimethylphenyl)- piperazin-2-one 1-(2-(4-Cyanophenyl)-2-propyl)-5-imidazolylmethyl]- 1 -(3-chlorophenyl)-5(S)-(2- methylsulfonylethyl)piperazin-2-one 5(S)-n-Butyl-4-[ I-(4-cyanobenzyl)-5-imidazolylmethyl]- 1 -(2-methylphenyl)piperazin-2- one 441 -(4-Cyanobenzyl)-5-imidazolylmethyl]-5(S)-(2-fluoroethyl)- 1 chlorophenyl)piperazin-2-one 4-[5-(4-Cyanobenzyl)- I -imidazolylethyl]- 1 -(3-chlorophenyl)piperazin-2-one or a stereoisomeric form, or a pharmaceutically acceptable acid or base addition salt form thereof, in a therapeutically effective amount.
256. 307. A method of treating a synucleinopathic subject, the method comprising, administering to a synucleinopathic subject a farnesyl transferase inhibitor compound selected from the list consisting of: 1 -(3-Trifluoromethoxyphenyl)4-[ I-(4-cyanobenzyl)imidazolylmethyl]-2-piperazinone 1 Dimethylphenyl)-4- [1 -(4-cyanobenzyl)imidazolylmethyl] -2-piperazi none 1 -Methyl phenyl)-4- [1 -(4-cyanobenzyl)imidazo lylmethyl ]-2-piperazi none 1I(NDohnl-4[1-4caoezy~mdzllehy]2pprznn 1 -(3-Coophenyl)-4-[ -(3moy4-cyanobenzyl)imidazolylmethyl]-2-piperazinone 1-3-hoohnC--[-3-m toy4caoezli ia)lIm ty]--ieainn o ~1 -Trifluoromethoxyphenyl)-4- [1-(3-methoxy-4-cyanobenzylimidazo)ylmethyl] -2- 00 piperazinone (R)-5-[(Benzyloxy)methyl]- I -(3-chlorophenyl)-4-[ I-(4-cyanobenzyl)-imidazolylmethyl]-2- piperazinone 1 -(3-Chlorophenyl)-4-[ 1-(2-fluoro-4-cyanobenzyl)- 1 H-imidazol-5-ylmethyl]piperazin-2- one I-(4-Cyanobenzyl)- I H-imidazol-5-ylmethyl]- 1 -(3-methylthiophenyl)piperazin-2-one C) 10 1-(4-Cyanobenzyl)- I H-imidazol-5-ylmethyl]- 1 -(3,5-dichlorophenyl)piperazin-2-one I -(3-Chlorophenyl)-4- f [1 -(4-cyanophenyl)- I1-ethyl]- 1 H-imidazol-5-ylmethyl)piperazin-2- one I -(3-Chloro-4-fluorophenyl)-4- 1-(4-cyanobenzyl)- 1 H-imidazol-5-ylmethyl]-piperazin-2- one I-(4-Cyanobenzyl)- 1 H-imidazol-5-ylmethyl]- 1 ,5-dimethylphenyl)piperazin-2-one (S)-5-Benzyl-4-[3-(4-cyanobenzyl-l1-imidazol-5-yl)prop- l-yl) -1 -phenyl-2-piperazinone 1 -Chilorophenyl)-4- [1 -(4-nitrobenzyl)- 1 H-imidazol-5-ylmethyl]piperazin-2-one 1-(4-Cyanobenzyl)- 1H-imidazol-5-ylmethyl]- 1-(3,5-difluorophenyl)piperazin-2-one 1-(4-Cyanobenzyl)- 1H-imidazol-5-ylmethyl]- I-(3,4-difluorophenyl)piperazin-2-one or a stereoisomeric form, or a pharmaceutically acceptable acid or base addition salt form thereof, in a therapeutically effective amount.
257. 308. A method of treating a synucleinopathic subject, the method comprising, administering to a synucleinopathic subject a famesyl transferase inhibitor compound of the formula: 429 \O or a stereoisomeric form, or a pharmaceutically acceptable acid or base addition salt form oO thereof, in a therapeutically effective amount, wherein: Rla and RIb are independently selected from: a) hydrogen, b) unsubstituted or substituted aryl, unsubstituted or substituted heterocycle, unsubstituted or substituted C 3 -CIo cycloalkyl, unsubstituted or substituted C 2 -C8 alkenyl, unsubstituted or substituted C 2 -C 8 alkynyl, R' 0 RoC(O)NR 0 (R'O) 2 (R' 0 2 NC(O)NR'-, CN, NO 2 -N(RIO) 2 or R"OC(O)NR'o-, or c) unsubstituted or substituted CI-C 6 alkyl wherein the substitutent on the substituted C 1 C 6 alkyl is selected from unsubstituted or substituted aryl, unsubstituted or substituted heterocycle, unsubstituted or substituted C 3 -CIO cycloalkyl, C 2 -C 8 alkenyl, C 2 -Cs alkynyl, R"oO-, RioC(0)NRio-, (RO)2NC(O)-, (RIO)2NC(0)NR'O-, CN, R -N(R' 0 2 and R'"'OC(O)NR'O-; R 2 and R 3 are independently selected from: H, unsubstituted or substituted C 1 6 alkyl, unsubstituted or substituted C 2 8 alkenyl, unsubstituted or substituted C2- 8 alkynyl, unsubstituted or substituted aryl, unsubstituted or substituted heterocycle, NR 6 R 7 OR 0 0 wherein the substituted group is substituted with one or more of: 1) aryl or heterocycle, unsubstituted or substituted with: a)Ci-6 alkyl, 6 b) (CH 2 )pOR, c) (CH 2 )pNR6R', d) halogen, e) CN, 2) C 3 -6 cycloalkyl, 430 3) OR 6 4) SR a, S(O)R a SOR~a -NRR' NR 6 R 7 NR' y NR 6 R 7 0 -S0 2 -NR 6 R 7 R 6 rL- 14 S0 2 ~R 6 a 14) N 3 or 16) F; or 431 R 2 and R 3 are attached to the same C atom and are combined to form -(CH 2 wherein N_ one of the carbon atoms is optionally replaced by a moiety selected from: 0, S(O)m, C.) 00 R 4 is selected from H and unsubstituted or substituted C I-C 6 alkyl; and any two of R R 3 or Rare optionally attached to the same carbon atom; R 5 is independently selected from: a) hydrogen, b) unsubstituted or substituted aryl, unsubstituted or substituted heterocycle, IND unsubstituted or substituted C 3 -C 10 cycloalkyl, unsubstituted or substituted C 2 -C 8 alkenyl, unsubstituted or substituted C 2 -C 8 alkynyl, perfluoroalkyl, halo, R' 0 unsubstituted or substituted C I-C 6 alkoxy, R" 1S(O)m, R' 0 0C(O)NR' 0 (R' 0 2 NC(O)-, (R' 0 2 NC(O)NR' 0 CN, NO 2 R' 0 R" 0 2 or R"'OC(O)NR'- and C) C I-C 6 alkyl, unsubstituted or substituted by aryl, cyanophenyl, heterocycle, C 3 -C 10 cycloalkyl, C 2 -C 8 alkenyl, C 2 -C8 alkynyl, perfluoroalkyl, F, Cl, Br, R 1 0 R R' 0 C(O)NR' 0 2 (R' 0 2 NC(O)NR' 0 CN, R 1 0 R' 0 R' 'OC(O)NR' 0 R 6 R 7 and R 7 a are independently selected from: H, C I-C 6 alkyI, C 3 6 cycloalkyl, heterocycle, aryl, aroyl, heteroaroyl, arylsulfonyl, heteroarylsulfonyl, unsubstituted or substituted with: a) C 1 6 alkoxy, b) C I-C 2 0 al kyl c) aryl or heterocycle, d) halogen, e) HO, f) g) -S0 2 R 1 1 ,or h) N(R' 0 2 or R 6 an 7 myb ondi ig and R 7 may be joined in a ring; R 6a is selected from: C I-C 6 alkyl, C3- 6 cycloalkyl, heterocycle, aryl, aroyl, heteroaroyl, arylsul fonyl, heteroarylsul fonyl, unsubstituted or substituted with: a) C1 4 alkoxy, b) C I-C 2 0 alkyl 432 c) aryl or heterocycle, d) halogen, o e) HO, 00 f)J-C(O)R 1 g) -SO 2 R',or h) N(R' 0 2 R 8is independently selected from: a) hydrogen, IND b) unsubstituted or substituted aryl, unsubstituted or substituted heterocycle, unsubstituted or substituted C 3 -CIO cycloalkyl, unsubstituted or substituted C 2 -C 8 alkenyl, unsubstituted or substituted C 2 -C 8 alkynyl, perfluoroalkyl, halo, R' 0 unsubstituted or substituted C,-C 6 alkoxy, R"S(O)m, R 10 C(O)NR" (R' 0 2 NC(O)-, (R' 0 2 NC(O)NR' 0 CN, NO 2 R' 0 R' 0 -N(R 0 2 or R' 'OC(O)NR' 0 and C) C I-C 6 alkyl unsubstituted or substituted by aryl, cyanophenyl, heterocycle, C 3 -C 10 cycloalkyl, C 2 -C 8 alkenyl, C 2 -C 8 alkynyl, perfluoroalkyl, halo, R' 0 R" R' 0 C(O)NR' 0 (R' 0 2 (R' 0 2 NC(O)NR' 0 CN, R' 0 R' 0 N(R' 0 2 or R'C(O)NR' 0 R 9 is selected from: a) hydrogen, b) unsubstituted or substituted aryl, unsubstituted or substituted heterocycle, unsubstituted or substituted C 3 -CIO cycloalkyl, unsubstituted or substituted C 2 -C 8 alkenyl, unsubstituted or substituted C 2 -Cg alkynyl, perfluoroalkyl, halo, R 10 R R' 0 C(O)NR' 0 (R' 0 2 (R' 0 2 NC(O)NR' 0 CN, NO 2 R 0 R' 0 0C(O)-, -N(R 0 2 or R"OC(O)NR' 0 and C) C I-C 6 alkyl unsubstituted or substituted by aryl, heterocycle, C 3 -C 1 0 cycloalkyl, perfluoroalkyl, halo, R' 0 R' 0 C(O)NR' 0 (R' 0 2 NC(O)-, (R' 0 2 NC(O)NR' 0 CN, R' 0 R' 0 -N(R' 0 2 or R"'OC(O)NR' 0 R' 0 is independently selected from hydrogen, unsubstituted or substituted C 1 -C 6 alkyl, perfluoroalkyl, unsubstituted or substituted aralkyl, and unsubstituted or substituted aryl; R1 is independently selected from unsubstituted or substituted C 1 -C 6 alkyl and unsubstituted or substituted aryl; A' and A 2 are independently selected from: a bond, -C(O)NR' 0 -NR' 0 0, -S(O) 2 N(R' 0 -N(R' 0 )S(O) 2 or 433 N_ A 3 is selected from -C(Rla 2 0, -N(R' 0 and oG' or G 2is selected from H1 2 or 0, provided that if G' is 0 then G 2is H1 2 and if G is 0S, 00 then G1is H 2 V is selected from: a) heterocycle, and b) aryl, W is a heterocycle; IND Y is heteroaryl; Z is a unsubstituted or substituted group selected from aryl, heteroaryl, arylmethyl, heteroarylmethyl, arylsulfonyl, heteroarylsulfonyl, wherein the substituted group is substituted with one or more of the following: I. Cl-C 6 alkyl, unsubstituted or substituted with: a) C 1 6 alkoxy, b) NR 6 R', C) C 3 6 cycloalkyl, d) aryl or heterocycle, e) HO, 6, f) S(O)mR ,or g) -C(O)NR 6 R', 2. unsubstituted or substituted aryl or unsubstituted or substituted heterocycle, 3. halogen, 4. OR 6 NR 6 R', 6. CN, 7. NO 2 8. CF 3 9.-S(O)mR 6 -C(O)NR 6 R', 11. -OCF 3 12. unsubstituted or substituted C 1 4 alkoxy, 13. C 2 -C 8 alkenyl, 14. C 2 -Csalkynyl, or C 3 -C 10 cycloalkyl; IO 0 m is 0, 1 or 2; n is 0, 1, 2, 3 or 4; Spis0,1,2, 3 or4; 00 q is 0, 1 or 2; r is 0 to s is 0 or 1; t is 0 to Su is 4 or 5; and \D x is 0, 1, 2, 3or 4. S
258. 309. A method of treating a synucleinopathic subject, the method comprising, administering to a synucleinopathic subject a farnesyl transferase inhibitor compound of the formula: (R t R 3 A 3 (R 9 )q I Y SAI(CR2)nA2(CR 1 a2)n,- W (CRlb 2 )p N N- Z R or a stereoisomeric form, or a pharmaceutically acceptable acid or base addition salt form thereof, in a therapeutically effective amount, wherein: R l a and R l b are independently selected from: a) hydrogen, b) unsubstituted or substituted aryl, unsubstituted or substituted heterocycle, unsubstituted or substituted C 3 -Clo cycloalkyl, -N(R' 0 2 or, C 2 -C 8 alkenyl, or c) unsubstituted or substituted CI-C 6 alkyl wherein the sub stitutent on the substituted C 1 C 6 alkyl is selected from unsubstituted or substituted aryl, unsubstituted or substituted heterocycle, unsubstituted or substituted C 3 -CIO cycloalkyl, C 2 -C 8 alkenyl, R' 0 or N( 2 3 R 2and R 3are independently selected from: H, unsubstituted or substituted C 1 6 00 NR 6 R 7 0 wherein the substituted group is substituted with one or more of: 1) aryl or heterocycle, unsubstituted or substituted with: a) CjI-C 6 alkyl, NO b) (CH 2 )pOR c) (CH 2 )pNR R d) halogen, e) CN; 2. C 3 6 cycloalkyl; 3. OR 6 4. SR 6 S(O)R a, S0 2 R~a -NR 6 R', 6)6 N I N Y R 7 R~ 0 0R6 6 R 8) 0 -0 Y NR 6 9) 0 NR 6 R 7 0 00 11) S0 2 -NR 6 R 7 R 6 14) 0 N 3 or 16) F; or R 2and R 3 are attached to the same C atom and are combined to form -(CH 2 wherein one of the carbon atoms is optionally replaced by a moiety selected from: 0, -NC(O-, and -N(COR' 0 R 4 is selected from H and unsubstituted or substituted C I-C 6 alkyl; and any two of R R 3 or R 4 are optionally attached to the same carbon atom; R 5 is independently selected from: a) hydrogen, b) unsubstituted or substituted aryl, unsubstituted or substituted heterocycle, unsubstituted or substituted C 3 -C 10 cycloalkyl, unsubstituted or substituted C 2 -C 8 alkenyl, unsubstituted or substituted C 2 -C 8 alkynyl, perfluoroalkyl, halo, R1 0 unsubstituted or substituted C I-C 6 alkoxy, R' R' 0 C(O)NR' 0 (R' 0 2 NC(0H-, (R' 0 2 NC(O)NR' 0 CN, NO 2 R' 0 R' 0 -N(R 0 2 or R' OC(O)NR' 0 and C) CI-C 6 alkyl unsubstituted or substituted by aryl, cyanophenyl, heterocycle, C 3 -C 10 cycloalkyl, C 2 -C 8 alkenyl, C 2 -C 8 alkynyl, perfluoroalkyl, F, Cl, Br, R S(O)m- R' 0 C(O)NR' 0 (R' 0 2 (R' 0 2 NC(O)NR' 0 CN, R' 0 R' 0 R'"OC(O)NR' 0 R 6, R 7and R 7 aare independently selected from: H, CI-C 6 alkyl, C 3 6 cycloalkyl, heterocycle, aryl, aroyl, heteroaroyl, arylsulfonyl, heteroarylsulfonyl, unsubstituted or substituted with: a) C 1 6 alkoxy, b) C I-C 2 o alkyl c) aryl or heterocycle, o d) halogen, 00 e) HO, f) g) -SO 2 R1 ,or h) N(R 0)2; or R 6 and R 7 may be joined in a ring; R 7 7 IND and Ra may be joined in a ring; R a is selected from: C I-C 6 alkyl, C 3 6 cycloalkyl, heterocycle, aryl, aroyl, heteroaroyl, arylsulfonyl, hteroarylsulfonyl, unsubstituted or substituted with: a) C1 6 alkoxy, b) C I-C 2 o alkyl c) aryl or heterocycle, d) halogen, e) HO, g) -SO 2 R1 ,or h) N(R' 0 2 or R 8 is independently selected from: a) hydrogen, b) unsubstituted or substituted aryl, unsubstituted or substituted heterocycle, unsubstituted or substituted C 3 -C 10 cycloalkyl, unsubstituted or substituted C 2 -C 8 alkenyl, unsubstituted or substituted C 2 -C 8 alkynyl, perfluoroalkyl, halo, R' 0 unsubstituted or substituted C 1 -C 6 alkoxy, R' 1 R' 0 C(O)NR' 0 (R' 0 2 (R' 0 2 NC(O)NR' 0 CN, NO 2 R' 0 C(O>- R' 0 -N(R' 0 2 or R''OC(O)NR' 0 and C) CI-C 6 alkyl unsubstituted or substituted by aryl, cyanophenyl, heterocycle, C 3 -CI 0 cycloalkyl, C 2 -C8 alkenyl, C 2 -C8 alkynyl, perfluoroalkyl, F, Cl, Br, R 10 R" R' 0 C(O)NR' 0 (R' 0 2 (R' 0 2 NC(O)NR' 0 CN, R' 0 R,' 0 N(R' 0 2 or R'"OC(O)NR' 0 R 9 is selected from: a) hydrogen, b) unsubstituted or substituted aryl, unsubstituted or substituted heterocycle, unsubstituted or substituted C 3 -C 10 cycloalkyl, unsubstituted or substituted C 2 -C 8 alkenyl, unsubstituted or substituted C 2 -C 8 alkynyl, perfluoroalkyl, halo, R' 0 R' R'C(O)NR' 0 (R' 0 2 NC(O)NR' 0 R' 0 CN, NO 2 o N 3 -N(R 0)2, or R' OC(O)NR"- and 00 C) Cl-C 6 alkyl unsubstituted or substituted by aryl, heterocycle, C 3 -CIO cycloalkyl, perfluoroalkyl, halo, R' 0 R' 0 C(O)NR' 0 (R' 0 2 NC(O)-, (R' 0 2 NC(O)NR' 0 CN, R' 0 R' 0 -N(R' 0 2 or R"'OC(O)NR' 0 R 0is independently selected from hydrogen, unsubstituted or substituted C 1 -C 6 alkyl, perfluoroalkyl, unsubstituted or substituted aralkyl, and unsubstituted or substituted aryl; R" is independently selected from unsubstituted or substituted C I-C 6 alkyl and unsubstituted or substituted aryl; A'I and A 2 are independently selected from: a bond, -CH=CH-, C(O)NR' 0 -NR' 0 0, -N(R' 0 -S(O) 2 N(R' 0 -N(R 0 )S(O) 2 or S(O)m; A is selected from -C(Rla 2 0, -N(R' 0 and W is a heterocycle selected from imidazolyl, pyridyl, thiazolyl, indolyl, quinolinyl, isoquinolinyl and thienyl; Y is heteroaryl; Z is a unsubstituted or substituted group selected from aryl, heteroaryl, arylmethyl, heteroarylmethyl, arylsul fonyl, heteroarylsulfonyl, wherein the substituted group is substituted with one or more of the following: 1. C I-C 6 alkyl, unsubstituted or substituted with: a) C 1 6 alkoxy, b) NR 6R', C) C 3 6 cycloalkyl, d) aryl or heterocycle, e) HO, 6a f) 1 R 'or g) -C(O)NR 6R', 2. unsubstituted or substituted aryl or unsubstituted or substituted heterocycle, 3. halogen, 6 4. OR 6 7 NRR 6. CN, 7. NO 2 8. CF 3 9. -S(O)mR 6 a -C(O)NRR 7 O 11. C 3 -C 6 cycloalkyl, 00 12. -OCF 3 or 13. unsubstituted or substituted C -6 alkoxy; m is 0, 1 or 2; Sn is 0, 1,2, 3 or 4; Mr p is 0, 1, 2, 3or 4; 0 q is 0, 1 or 2; r is0 to t is 0 to u is 4 or 5; and x is0, 1,2, 3or 4.
259. 310. A method of treating a synucleinopathic subject, the method comprising, administering to a synucleinopathic subject a farnesyl transferase inhibitor compound of the formula: (R(R AI S R2 R3 (CRla N (R 8 )r (CRlb 2 )p N N- Z R 4 or a stereoisomeric form, or a pharmaceutically acceptable acid or base addition salt form thereof, in a therapeutically effective amount, 440 C.) 0O O IO wherein: R'a and RIb are independently selected from: a) hydrogen, b) unsubstituted or substituted aryl, unsubstituted or substituted heterocycle, unsubstituted or substituted C 3 -Co 10 cycloalkyl, unsubstituted or substituted C 2 -C 8 alkenyl, R' 0 or -N(RI)2, or c) unsubstituted or substituted CI-C 6 alkyl wherein the substitutent on the substituted C 1 -C 6 alkyl is selected from unsubstituted or substituted aryl, unsubstituted or substituted heterocycle, unsubstituted or substituted C 3 -C 1 lo cycloalkyl, C 2 -C 8 alkenyl, R' 0 or -N(RI1)2; NR 6 R 7 R 2 is H, unsubstituted or substituted C 1 6 alkyl, or O wherein the substituted group is substituted with one or more of: 1) aryl, 2) heterocycle, 3) OR 6 4) SR 6 a, SO 2 R 6 a, or NR 6 R 7 5) 0 R 3 and R 4 are independently selected from H and unsubstituted or substituted CI-C 6 alkyl; and any two of R 2 R or R4 are optionally attached to the same carbon atom; R 5 is independently selected from: a) hydrogen, b) unsubstituted or substituted aryl, unsubstituted or substituted heterocycle, unsubstituted or substituted C 3 -Co 10 cycloalkyl, unsubstituted or substituted C 2 -C 8 alkenyl, unsubstituted or substituted C 2 -C 8 alkynyl, perfluoroalkyl, halo, Ro 10 unsubstituted or substituted CI-C 6 alkoxy, R' RoC(O)NR'o-, (R' 0 2 (RI) 2 NC(O)NR-, CN, NO 2 R 1 -N(R' 0 2 or R'"OC(O)NR'o-, and c) CI-C 6 alkyl unsubstituted or substituted by aryl, cyanophenyl, heterocycle, C 3 -Co 0 cycloalkyl, perfluoroalkyl, F, CI, Br, R 0 R'oC(O)NRo-, (RI 0 2 NC(O)-, (RI 0 2 NC(O)NR 0 CN, R'OOC(O)-, -N(RI 0 2 or R'1OC(O)NRIO-; R 6 and R 7 are independently selected from: H, C 1 -C 6 alkyl, C 3 6 cycloalkyl, heterocycle, aryl, unsubstituted or substituted with: a) C 1 6 alkoxy, b) C I-C 2 0 alkyl c) aryl or heterocycle, 00 d) halogen, or e) HO; R 6 and R 7 may be joined in a ring; R 6 i selected from: C I-C 6 alkyl, C 3 6 cycloalkyl, heterocycle, aryl, aroyl, heteroaroyl, arylsulfonyl, heteroarylsulfonyl, unsubstituted or substituted with: a) C 1 6 alkoxy, IND C I-C 2 0 alkyl c) aryl or heterocycle, d) halogen, or e) HO; R 8 is independently selected from: a) hydrogen, b) unsubstituted or substituted aryl, unsubstituted or substituted heterocycle, unsubstituted or substituted C 3 -C 10 cycloalkyl, unsubstituted or substituted C 2 -C 8 alkenyl, unsubstituted or substituted C 2 -C 8 alkynyl, perfluoroalkyl, halo, R1 0 unsubstituted or substituted C I -C 6 al koxy, R' 11S(O)mn-, R' 0 C(O)NR' 0 (R1 0 2 NC(O), (R1 0 2 NC(O)NR 0 CN, NO 2 R' 0 R' 0 -N(R 0 2 or R"OC(O)NR' 0 and C) C 1 -C 6 alkyl unsubstituted or substituted by aryl, cyanophenyl, heterocycle, C 3 -CI 0 cycloalkyl, perfluoroalkyl, halo, R' 0 R' 0 C(O)NR' 0 (R' 0 2 NC(O)-, 2 ,NC(O)NR' 0 CN, R' 0 R' 0 -N(R 10)2, or R' 0 0C(O)NR' 0 R 9 is selected from: a) hydrogen, b) unsubstituted or substituted aryl, unsubstituted or substituted heterocycle, unsubstituted or substituted C 3 -C 10 cycloalkyl, unsubstituted or substituted C 2 -C 8 alkenyl, unsubstituted or substituted C 2 -Csalkynyl, perfluoroalkyl, halo, R 0 R' 0 C(O)NR' 0 (R' 0 2 (R' 0 2 NC(O)NR' 0 CN, NO 2 R' 0 R' 0 -N(R 0 2 or R' 1 0C(O)NR 1 and C) C 1 -C 6 alkyl unsubstituted or substituted by aryl, heterocycle, C 3 -CiOcycloalkyl, perfluoroalkyl, halo, R' R" R 'C(O)NR' 0 2 NC(O>-, (R' 0 2 NC(O)NR' 0 CN, R' 0 R' 0 -N(R' 0 2 or R''0C(O)NR' 0 R1 0 is independently selected from hydrogen, unsubstituted or substituted C I-C 6 alkyl, perfluoroalkyl, unsubstituted or substituted aralkyl, and unsubstituted or substituted aryl; OD R" is independently selected from unsubstituted or substituted CI-C 6 alkyl and unsubstituted S or substituted aryl; o A is selected from -C(Rla)2-, 0, and S(O)m; 00 Y is heteroaryl; Z is a unsubstituted or substituted group selected from aryl, heteroaryl, arylmethyl, heteroarylmethyl, wherein the substituted group is substituted with one or more of the following: 1. CI-C 6 alkyl, unsubstituted or substituted with: IO0 a) C-6 alkoxy, b) NR6R 7 c) C 3 6 cycloalkyl, d) aryl or heterocycle, e) HO, f) -S(O)mR, or g) -C(O)NR6R 2. unsubstituted or substituted aryl or unsubstituted or substituted heterocycle, 3. halogen, 4. OR 6 NR6R, 6. CN, 7. NO 2 8. CF 3 9. -S(O)mR 6 -C(O)NR 6 R 7 11. C 3 -C 6 cycloalkyl, 12. -OCF 3 or 13. unsubstituted or substituted C 1 6 alkoxy; m is 0, 1 or 2; n is 0, 1,2, 3or 4; p is 0, 1,2, 3or 4; q is 0, 1 or 2; r is 0 to t is 0 to 5; and u is 4 or
260. 311. A method of treating a synucleinopathic subject, the method comprising, administering to a synucleinopathic subject a farnesyl transferase inhibitor compound of the list o comprising. of: 00 (3-chlorophenyl)-4-[ 1-(3 -(3-pyridyloxy)-4-cyanobenzyl)-5-imidazolylmethyl]-2- piperazinone; and I -(2-(n-Butyloxy)phenyl)-4- -((6-methyl-2-pyridyl)oxy)-4-cyanobenzyl)-2-methyl- -iiidazolyl methyl ]-2-pi perazi none; or a stereoisomeric form, or a pharmaceutically acceptable acid or base addition salt form IND thereof, in a therapeutically effective amount.
261. 312. A method of treating a synucleinopathic subject, the method comprising, administering to a synucleinopathic subject a farnesyl transferase inhibitor compound selected from the list consisting of: 1 -(3-chlorophenyl)-4-[ 1-(3-((2-chlorophenyl)oxy)-4-cyanobenzyl)-5-imidazolylmethyl]-2- piperazinone; 1 -(3-chlorophenyl)-4-[ 1-(3-((3-chlorophenyl)oxy)-4-cyanobenzyl)-5- imidazolylmethyl]-2-piperazinone; 1 -(3-chlorophenyl)-4-[ I-(3-((4-chlorophenyl)oxy)-4- -2-piperazinone; 1 -chlorophenyl)-4- [1 bi pheny lylI)oxy)-4-cyanobenzyl)- 5-imidazolylmethyl] -2-piperazi none; 1 -chlorophenyl)-4-[ 1- -(2-hydroxy- 1 -ethoxy)phenyl)oxy)-4-cyanobenzyl)-5-imidazolylmethyl]-2-piperazinone; 1 -(3-chlorophenyl)-4- [1-(3-((4-(benzyloxy)phenyl)oxy)-4-cyanobenzyl)-5 -imidazolylmethyl] 2-piperazinone; and 1 -(2-(n-Butyloxy)phenyl)-4- -(2-hydroxy-l1-ethoxy)phenyl)oxy)-4- cyanobenzyl)-2-methyl-5-imidazolylmethyl]-2-piperazinone or a stereoisomeric form, or a pharmaceutically acceptable acid or base addition salt form thereof, in a therapeutically effective amount.
262. 313. The method of claim 312, wherein the compound is I-(3-chlorophenyl)-4-[1-(3- ((2-chlorophenyl)oxy)-4-cyanobenzyl)-5 -iminidazolylmethyl] -2-piperazi none.
263. 314. The method of claim 312, wherein the compound is 1-(3-chlorophenyl)-4-[1-(3- -chlorophenylI)oxy) -4-cyanobenzyl)-5 imidazolylmethyl] -2-pi perazi none.
264. 315. The method of claim 312, wherein the compound is 1-(3-chlorophenyl)-4-[1-(3- ((4-chl orophenyl)oxy)-4-cyanobenzyl)- 5 -im idazolyl methyl] -2 -pi perazi none.
265. 316. he method of claim 312, wherein the compound is 1-(3-chlorophenyl)-4-[1-(3- iphenyl yl)oxy)-4-cyanobenzyl)-5 -imidazolyl methyl ]-2-piperazi none. 00 317. The method of claim 312, wherein the compound is 1-(3-chlorophenyl)-4-[1-(3- -(2-hydroxy- 1 -ethoxy)phenyl)oxy)-4-cyanobenzyl)-5 -imidazolylmethyl] -2-piperazinone.
266. 318. The method of claim 312, wherein the compound is 1 -(3-chlorophenyl)-4-[ 1-(3- ((4-(benzyl oxy)phenyl)oxy)-4-cyanobenzyl)-5 imidazolyl methyl -2-pi perazi none.
267. 319. The method of claim 312, wherein the compound is 1 -(2-(n-Butyloxy)phenyl)-4- [1 -(3-((3-(2-hydroxy- I -ethoxy)phenyl)oxy)-4-cyanobenzyl)-2-methyl-5-midazolylmethyl]-2- piperazinone.
268. 320. A method of treating a synucleinopathic subject, the method comprising, administering to a synucleinopathic subject a famnesyl transferase inhibitor compound selected from the list consisting of: 2(S)-Butyl-l1-(2,3-diaminoprop- l-yl)-l -naphthoyl)piperazine; I -(3-Amino-2-(2- naphthylmethylamino)prop-1I-yl)-2(S)-butyl-4-( I-naphthoyl)piperazine; 2(S)-Butyl- 1- (2-naphthylmethyl)]-4,5-dihydroimidazol }methyl-4-( I-naphthoyl)piperazine; 1 1- Benzylimidazol)methyl]-2(S)-butyl-4-( I-naphthoyl)piperazine; 1- 1-(4- nitrobenzyl)] imidazolylmethyl }-2(S)-butyl-4-( 1-naphthoyl)piperazine; 1 Acetamidomethylthio-2(R)-aminoprop-1I-yl)-2(S)-butyl-4-( 1-naphthoyl)piperazine; 2(S)- Butyl-l1-[2-( I-imidazolyl)ethyl]sulfonyl-4-( 1-naphthoyl)piperazine; 2(R)-Butyl- 1- imidazolyl-4-methyl-4-( 1 -naphthoyl)piperazine; 2(S)-Butyl-4-( 1 -naphthoyl)- 1 pyridylmethyl)piperazine; I -2(S)-butyl-(2(R)-(4-nitrobenzyl)amino-3-hydroxypropyl)-4-(1 naphthoyl)piperazine; I -(2(R)-Amino-3 -hydroxyheptadecyl)-2(S)-butyl-4-( I-naphthoyl)- piperazine; 2(S)-Benzyl- 1 -imidazolyl-4-methyl-4-( 1 -naphthoyl)piperazine; 1 -(2(R)-Amino- 3-(3-benzylthio)propyl)-2(S)-butyl-4-( I-naphthoyl)piperazine; 1 -(2(R)-Amino-3-[3-(4- nitrobenzylthio)propyl])-2(S)-butyl-4-( 1-naphthoyl)piperazine; 2(S)-Butyl- 1 imidazolyl)ethyl]-4-( 1 -naphthoyl)piperazine; 2(S)-Butyl- I -[(4-imidazolyl)methyl]-4-( 1- naphthoyl)piperazine; 2(S)-Butyl-l1-[(1 -naphth-2-ylmethyl)- 1H-imidazol-5-yl)acetyl]-4-( 1- naphthoyl)piperazine; 2(S)-Butyl-l1-[(1 -naphth-2-ylmcthyl)- 1H-imidazol-5-yl)ethyl]-4-( 1- naphthoyl)piperazine; I -(2(R)-Amino-3 -hydroypropyl)-2(S)-butyl-4-( I naphthoyl)piperazine; 1 -(2(R)-Amino-4-hydroxybutyl)-2(S)-butyl-4-( 1- INDhy~ieaie (-Aio3-2bnyoyhni~rpl-()btl4(1 naphthoyl)piperazine; I -(2-Amino-3-(2-heyoxyphenyl)propyl)-2(S)-butyl-4-( 1- nahhy0ieaie -2Aio3(-hdoyhnlpoy)2S-uy--I o naphthoyl)piperazine; 1 -[3-(4-imidazolyl)propyl]-2(S)-butyi-4-( I-naphthoyl)-piperazine; 00 2(S)-n-Butyl-4-(2,3-dimethylphenyl)- 1-(4-imidazolylmethyI)-piperazin-5 -one; 2(S)-n- ButyI- 1-r[I -(4-cyanobenzyl)imidazol-5 -yl methyl] -dimethyl pheny I)pi perazin- 1-[ri -(4-Cyanobenzyl)imidazol-5-ylmethyl]-4-(2,3-dimethylphenyl)-2(S)-(2- -one; 2(S)-n-Butyl-4-( 1-naphthoyI)-1-ri 2(S)-n-Butyl-4-( I -naphthoyl)- I 1 1-10 naphthylmethyl)imidazoi-5-ylmethyl]-piperazine; 2(S)-n-Butyl- 1-[i1 C) 10 cyanobenzyl)imidazol-5-ylmethyl]-4-( 1-naphthoyl)piperazine; 2(S)-n-Butyl-i-ri methoxybenzyI)imidazoi-5-ylmethyl]-4-( I-naphthoyl)piperazine; 2(S)-n-Butyl- i-ri-(3- methyl-2-butenyl)imidazol-5-ylmethyl-4-( I -naphthoyl)piperazine; 2(S)-n-ButyI-[ -r fluorobenzyl)imidazol-5-yimethyl]-4-( 1-naphthoyl)piperazine; 2(S)-n-Butyl-i-rI chlorobenzyl)imidazol-5-ylmethyI]-4-( I-naphthoyl)piperazine; i-ri Bromobenzyl)imidazol-5-ylmethyl]-2(S)-n-butyl-4-( 1-naphthoyI)piperazine; 2(S)-n-Butyl- 1 -naphthoyl)- 1 -[1I -(4-trifluoromethyibenzyi)imidazol-5-ylmethyI]-piperazine; 2(S)-n- IButyI I -(4-methylbenzyI)imidazol-5-ylmethyl]-4-( I -naphthoyl)-piperazine; 2(S)-n- Butyl- i-ri-(3-methylbenzyl)imidazol-5-ylmethyl]-4-( 1-naphthoyl)-piperazine; i-ri Phenylbenzyl)imidazol-5-ylmethyl]-2(S)-n-butyl-4-( i -naphthoyl)-piperazine; 2(S)-n-Butyl- i-naphthoyl)- i-ri-(2-phenylethyi)imidazol-5-ylmethyi]-piperazine; 2(S)-n-Butyl-4-( i- naphthoyl)- i-ri-(4-trifluoromethoxy)imidazoi-5-ylmethyl]piperazine; 1-1 [1 i-(4- cyanobenzyi)- I H-imidazol-5-yl]acetyl]-2(S)-n-butyl-4-( I -naphthoyI)piperazine; 1-(3- Chlorophenyl)-4-r 1-(4-cyanobenzyl)-5-imidazolylmethyl]-5-r2-(methanesuifonyi)ethy]-2- piperazinone; 1-(3 -Chlorophenyl)-4-r 1-(4-cyanobenzyi)-5-imidazoiylmethyl]-5-[2- (ethanesul fonyl)ethyl] -2-piperazi none; I-(3-Chlorophenyl)-4-r imidazolylmethyi]-5-r2-(ethanesulfonyi)methyl]-2-piperazinone; i-(3 -Chlorophenyl)-4- [i -(4-cyanobenzyI)-5-imidazolylmethyl]-5 -[N-ethyl-2-acetamido] -2-piperazi none; Butynyl)- 1 -chlorophenyl1)-4-r [1 -(4-cyanobenzyl)-5 -im idazo lyl methyl] -2-pi perazi none; I (3 -C h orophenyi)-4 I -(4-cyanobenzyl)-5 -imidazolyl methyl] -2-pi perazi none; 5(S)-Butyl-4- [1 -(4-cyanobenzyl-2-methyl)-5-imidazolylmethyl]- I-(2,3-dimethylphenyl)-piperazin-2-one; 4-ri -(2-(4-Cyanophenyl)-2-propyi)-5-imidazoiylmethyl]- I -(3-chlorophenyl)-5(S)-(2- methylsulfonylethyl)piperazin-2-one; 5(S)-n-Butyl-4-ri imidazolylmethyl]-(2-methylphenyl)piperazin-2-one; 4-ri im idazo lyl methyI] 5(S)-(2-fl uoroethyl)- 1 -chi orophenyI)piperazi n-2 -one; Cyanobenzyl)pyridin-4-yl]- I -(3-chlorophenyl)-5(S)-(2-methylsulfonylethyl)-piperazin-2- __one; 4- [5 -(4-Cyanobenzyl)- I -i midazo lyl ethyl] 1 -chlorophenyl)pi perazi n-2-one; 4- o (-2-Oxo-2-H-pyridin- 1-yI)benzyl-3-H-imidazol-4-ylmethyl]benzonitrile; 4- {3-[4-3-Methyl- 00 2-oxo-2-H -pyri din- 1 -yl)benzyl -H-i midazol-4-yl methyl] benzonitrilIe; piperidin- 1-yl)benzyl]-3-H-imidazol-4-ylmethyl]benzonitrile; 4- -Methyl-4-(2- oxopiperidin- 1-yl)-benzyl]-3-H-imidizol-4-ylmethyl }-benzonitrile;, (4-f{3 -[4-(2-Oxo- pyrrolidin- 1-yl)-benzyl]-3H-imidizol-4-ylmethyl)}-benzonitrile; 4-1 3-[4-(3-Methyl-2-oxo-2- H-pyrazin- 1-yI)-benzyl-3-H-imidizol-4-ylmethyl }-benzonitrile; 4- {3-[2-Methoxy-4-(2-oxo- 2-H-pyridin- 1-yI)-benzyl]-3-H-imidizol-4-ylmethyl)}-benzonitrile; 4-{(1-[4-(5-Chloro-2- oxo-2H-pyridin-1I-yI)-benzyl]- 1H-pyrrol-2-ylmethyl)}-benzonitrile; 1-(2-Oxo-2H- [1 ,2']bipyridinyl-5 '-ylmethyl)- 1 H-pyrrol-2-ylmethyl]-benzonitrile; 1-(5-Chloro-2-oxo- 2H-[ 1,2']bipyridinyl-5 '-ylmethyl)- IH-pyrrol-2-ylmethyl]-benzonitrile; 4-[3-(2-Oxo- 1- phenyl- 1,2-dihydropyridin-4-ylmethyl)-3H-imidazol-4-ylmethyl]benzonitrile; 1-(3- Chloro-phenyl)-2-oxo- 1 ,2-dihydropyridin-4-ylmethyl]-3H-imidazol-4- ylmethyl }benzonitrile; I 9,20-Dihydro- 19-oxo-5H, 17H- 18,21 -ethano-6, 10:12,16- dimetheno-22H-imidazo[3,4-h] [1,8,11,1 4]oxatriazacycloeicosine-9-carbonitrile; 1 9-Chioro- 22,23-dihydro-22-oxo-5H-21I,24-ethano-6,1 I -metheno-25H-dibenzo[b,e] imidazo[4,3- 1] [1,4,7,10,1 3]dioxatriazacyclononadecine-9-carbonitrile; 22,23-Dihydro-22-oxo-5H-2 1,24- ethano-6, I 0-metheno-25H-dibenzo[b,e]imidazo[4,3- 1] [1,4,7,10,13 ]dioxatriazacyclononadecine-9-carbonitrile; 20-Chloro-23 ,24-dihydro-23 -oxo- 5H-22',25-ethano-6, 10:12,1 6-dimetheno- 1 2H,26H-benzo[b]imidazo[4,3- i] [1,1 7,4,7,1 0]dioxatriazacyclohemicosine-9-carbonitrile; (S)-20-Chloro-23 ,24-dihydro-27- [2-(methylsulfonyl)ethyl]-23-oxo-5H-22,25-ethano-6, 10:12,1 6-dimetheno- I 2H,26H- benzo[b] imidazo[4,3-i] [1,17,4,7,1 0]dioxatriazacyclohemicosine-9-carbonitri le; 19,20- Dihydro- 19-oxo-5H- 18,21 -ethano- 12,1 4-etheno-6,1I -metheno-22H-benzo[d] imidazo[4,3- k] [1,6,9,1 2]oxatriazacyclooctadecine-9-carbonitrile; 19,20-Dihydro-1I9-oxo-5 H- 18,21 ethano- 12,1 4-etheno-6,1I0-metheno-22H-benzo[d]imidazo[4,3- k] 1,6,9,1 2]oxatriazacyclooctadecine-9-carbonitrile; 1 9,20-Dihydro- I 9-oxo-5H- 18,2 1 ethano-1I 2,1 4-etheno-6, 1 0-metheno-22H-benzo[d] imidazo[4,3- k] [1,6,9,1 2]oxatriazacyclooctadecine-9-carbonitrile; 5H, 17H,20H- 18,21 -Ethano-6, 10:12,16- dimetheno-22H-imidazo[3,4-h] 1,8,11,1 4]oxatriazacycloeicosin-20-one; 19,20- Dihydro-3-methyl- 1 9-oxo-5H- 18,21 -ethano- 1 2,1 4-etheno-6, 1 0-metheno-22H- benzo[d] imidazo[4,3 [1,6,9,1 2]oxatriazacyclooctadecine-9-carbonitrile; or 19,20- Dihydro-3-methyl-1I9-oxo-5H- 18,21 -ethano- 12,1 4-etheno-6,1I0-metheno-22H- benzo[d]imidazo[4,3-k] 1,6,9,1 2]oxatriazacyclooctadecine-9-carbonitrile; (Enantiomer A) 1 9,20-Dihydro-3-methyl- 1 9-oxo-5H- 18,2 1 -ethano- 1 2,1 4-etheno-6,1 I -metheno- o 22H-benzo[d] imidazo[4,3-k] [1,6,9,1 2]oxatriazacyclooctadecine-9-carbonitrile; (Enantiomer 00 B) 1 9,20-Dihydro- I 9,22-dioxo-5H- 18,2 1 -ethano- 1 2,1 4-etheno-6, 1 O-metheno-22H- benzo[d]imidazo[4,3-k] [1,6,9,1 2]oxatriazacyclooctadecine-9-carbonitrile; 325 18,19- dihydro-1I9-oxo-5H, 1 7H-6, 10:12, 1 6-dimetheno-lIH-imidazo[4,3- c] [1,l1,4]dioxaazacyclononadecine-9-carbonitrile; 17,1 8-dihydro- 1 8-oxo-5H-6, 10:12,16- dimetheno- I 2H,20H-imidazo[4,3-c] 1, 1 1,4]dioxaazacyclooctadecine-9-carbonitrile; IND17,18,1 9,20-tetrahydro- I 9-phenyl-5H-6, 10:12,1 6-dimetheno-2 1 H-imidazo[3,4- h] [1,8,11 ]oxadiazacyclononadecine-9-carbonitrile; 21 ,22-dihydro-5H-6, 10:12,16- dimetheno-23H-benzo[g] imidazo[4,3- 1] [1,8,11I ]oxadiazacyclononadecine-9-carbonitrile; 22,23-dihydro-23 -oxo-5H,2 1H-6, 10:12,1 6-dimetheno-24H-benzo g] imidazo[4,3- m] [1,8,1 2]oxadiazaeicosine-9-carbonitrile; 22,23-dihydro-5H,2 1H-6, 10:12,1 6-dimetheno- 24H-benzo[g]imidazo[4,3-m] [1,8,11 ]oxadiazaeicosine-9-carbonitrile; 1 tri fluoromethoxyphenyl)-4- [1-(4-cyano-3 -methoxybenzyl)-5-imidazolyI methyl] -2- piperazinone; or a pharmaceutically acceptable salt, stereoisomer or optical isomer thereof. Specific examples of a farnesyl -protein transferase inhibitor are 1-(3-Chlorophenyl)-4-[1 (4-cyanobenzyl)-5-imidazolylmethyl]-2-piperazinone; 1-(3-Chlorophenyl)-4-[l1-(4- cyanobenzyl)-5-imidazolylmethyl]-5-[2-(ethanesulfonyl)methyl]-2-piperazinone; Chloro-2-oxo-2H-[1I,2']bipyridinyl-5 '-ylmethyl)- 1H-pyrrol-2-ylmethyl]-benzonitrile; and I- 1 -(4-cyanobenzyl)-5-imidazolylmethyl)-N-(4-cyanobenzyl)amino]-4- (phcnoxy)benzene; 19,20-Dihydro- 19-oxo-5H- 18,21 -ethano- 12, 1 4-etheno-6, metheno-22H-benzo[d]imidazo[4,3-k] [1,6,9,1 2]oxatriaza-cyclooctadecine-9-carbonitrile; 1- (3 -tri fluoromethoxyphenyl)-4- [1-(4-cyano-3 -methoxybenzyl)-5-imidazolyI methyl] -2- piperazinone; 3-(biphenyl-4-ylmethoxy)-4-imidazol-1I-ylmethyl-benzonitrile; 3-(biphenyl-4- yl-2-ethoxy)-4-imidazol-1I-ylmethylbenzonitrile; 3-(biphenyl-3-ylmethoxy)-4-imidazol- 1- ylmethyl-benzonitrile; 2-(biphenyl-4-ylmethoxy)-4-imidazol- 1-ylmethyl-benzonitrile; 2- (biphenyl-4-yl-2-ethoxy)-4-imidazol-1I-ylmethyl-benzonitrile; I -tert-butoxycarbonyl-4-(3- chlorophenyl)-2(S)-[2-(2-cyano-5-imidazol- 1-ylmethyl-phenoxy)ethyl]piperazine; 2-(3- chlorophenoxy)-4-imidazol- 1 -ylmethyl-benzonitrile; 2-(4-chlorophenyl-2-ethoxy)-4- imidazol-1I-ylmethyl-benzonitrile; 2-(3-chlorophenyl-2-ethoxy)-4-imidazol-1I-ylmethyl- benzonitrile; 2-(2-chlorophenyl-2-ethoxy)-4-imidazol- 1-ylmethyl-benzonitrile; 2-(phenyl-2- ethoxy)-4-imidazol- 1 -ylmethyl-benzonitrile; 2-(3-chlorobenzyloxy)-4-imidazol- 1 -ylmethyl- benzonitrile; 2-(4-chlorobenzyloxy)-4-imidazol-1I-ylmethyl-benzonitrile; 2-(2,4- 448 dichlorobenzyloxy)-4-imidazol- 1 -ylmethyl-benzonitrile; 2-(benzyloxy)-4-imidazol- 1 ylmethyl-benzonitrile; 2-(biphenyl-2-ylmethoxy)-4-imidazol- 1-ylmethyl-benzonitrile; 2- o (phenyl-4-butoxy)-4-imidazol- 1 -ylmethyl-benzonitrile; 2-(phenyl-3-propoxy)-4-imidazol- 1 00 ylmethyl-benzonitrile; 2-(biphenyl-4-yl-2-ethoxy)-4-( 1,2,4-triazol- I -yI)methyl-benzonitrile; 2-(biphenyl-4-yl-2-ethoxy)-4-(2-methyl-imidazol- I -yl)methyl-benzonitri le; 2-(biphenyl-4- yI-2-ethoxy)-4-benzimidazol- I -yl)methyl-benzonitri le; 4-imidazol- 1 -ylmethyl-2- (naphthalen-2-yloxy)-benzonitrile; 2-(3 -cyanophenoxy)-4-imidazol- I -ylmethyl- benzonitrile; 2-(3 -bromophenoxy)-4-imidazol- 1-ylmethyl-benzonitrile; 2-(biphen-3-yloxy)- IND 4-imidazol- 1 -ylmethyl-benzonitrile; 2-(biphen-4-yloxy)-4-imidazol- I -ylmethyl- benzonitrile; 2-(3-acetylphenoxy)-4-imidazol- 1-ylmethyl-benzonitrile; 2-(2-acetylphenoxy)- 4-imidazol-1I-ylmethyl-benzonitrile; 2-(3-trifluoromethylphenoxy)-4-imidazol- 1-ylmethyl- benzonitrile; 2-(3-methylphenoxy)-4-imidazol- 1-ylmethyl-benzonitrile; 2-(2- methylphenoxy)-4-imidazol- 1 -ylmethyl-benzonitrile; 2-(4-methylphenoxy)-4-imidazol- 1 ylmethyl-benzonitrile; 2-(3-methoxyphenoxy)-4-imidazol- 1-ylmethyl-benzonitrile; 2-(2- methoxyphenoxy)-4-imidazol- 1-ylmethyl-benzonitrile; 2-(4-methoxyphenoxy)-4-imidazol- 1 -ylmethyl-benzonitrile; 2-(3,5-dimethylphenoxy)-4-imidazol- 1-ylmethyl-benzonitrile; 2- (3,4-dimethylphenoxy)-4-imidazol-1 -ylmethyl-benzonitrile; 2-(3,5-dimethoxyphenoxy)-4- imidazol- 1 -ylmethyl-benzonitrile; 2-(l1 -naphthyloxy)-4-imidazol- 1 -ylmethyl-benzonitrile; 2-(2,4-dichlorophenoxy)-4-imidazol- 1-ylmethyl-benzonitrile; 2-(3-fluorophenoxy)-4- imidazol- 1-ylmethyl-benzonitrile; 2-(3-t-butylphenoxy)-4-imidazol-1I-ylmethyl- benzonitrile; 2-[3-(N,N-diethylamino)phenoxy]-4-imidazol- 1-ylmethyl-benzonitrile; 2-(3-n- propylphenoxy)-4-imidazol- 1-ylmethyl-benzonitrile; 2-(2,3 -dimethoxyphenoxy)-4- imidazol- 1-ylmethyl-benzonitrile;, 2-(2,3-dimethylphenoxy)-4-imidazol- I-ylmethyl- benzonitrile; 2-(3 ,4-dirnethoxyphenoxy)-4-imidazol- 1 -ylmethyl-benzonitri le; 2-(2,5- dimethoxyphenoxy)-4-imidazol-1I-ylmethyl-benzonitrile; 2-(3 ,4-dichlorophenoxy)-4- imidazol- I -ylmethyl-benzonitrile; 2-(2,4-dimethylphenoxy)-4-imidazol- 1 -ylmethyl- benzonitrile; 2-(4-chloro-2-methylphenoxy)-4-imidazol- 1-ylmethyl-benzonitrile; chloro-2-m-ethylphenoxy)-4-imidazol-1I-ylmethyl-benzonitrile; 2-(2-chloro-4,5- dimethylphenoxy)-4-imidazol- 1 -ylmethyl-benzonitrile; 2-(5-hydroxymethyl-2- methoxyphenoxy)-4-imidazol- I -ylmethyl-benzonitrile; 4-imidazol- 1 -ylmethyl-2-(3- phenylamino-phenoxy)-benzonitrile; 4-imidazolI- I -yl methyl-2- [3 -methyl phenyl amino)- phenoxy]-benzonitrile; 4-imidazol- 1-ylmethyl-2-(3-phenoxy-phenoxy)-benzonitrile; 2-(2- benzoyl-phenoxy)-4-imidazol- 1-ylmethyl-benzonitrile; 1 -(5-chloro-2-methoxy-phenyl)-3 [3-(2-cyano-5-imidazol- 1-ylmethyl-phenoxy)-phenyl]-urea; 1 -(2,5-dimethoxy-phenyl)-3-[3- -imidazol- 1-ylmethyl-phenoxy)-phenyl]-urea; 2-(3 -benzyloxy-phenoxy)-4- imidazol- 1 -ylmethyl-benzonitrile; 2-(4-benzyloxy-phenoxy)-4-imidazol- I -ylmethyl- o benzonitrile; 2-(2-benzyl-phenoxy)-4-imidazol- 1-ylmethyl-benzonitrile; 2-(3-ethynyl- 00 phenoxy)-4-imidazol- 1-ylmethyl-benzonitrile; 2-(4-acetyl-3 -methyl-phenoxy)-4-imidazol- 1 -ylmethyl-benzonitri le; 4-imidazol- 1 -ylmethyl-2-( I H-indazol-6-yloxy)-benzonitrile; 4- imidazol- 1-ylmethyl-2-(5,6,7,8-tetrahydro-naphthalen-1I-yloxy)-benzonitrile; 4-imidazol- 1- ylmethyl-2-(8-oxo-5,6,7,8-tetrahydro-naphthalen- I -yloxy)-benzonitrile; 4-imidazol- 1 ylmethyl-2-( I H-indol-7-yloxy)-benzonitrile; 4-imidazol- 1 -ylmethyl-2-(3 -oxo-indan-4- INDyloxy)-benzonitrile; 4-imidazol- 1-ylmethyl-2-( IH-indol-4-yloxy)-benzonitrile; hydroxy-ethoxy)-phenoxy]-4-imidazol- 1 -ylmethyl-benzonitrile; 4-imidazol- I -ylmethyl-2- (4-imidazol- I -yl-phenoxy)-benzonitrile; 4-(2-cyano-5-imidazol- I -ylmethyl-phenoxy)- biphenyl-4-carbonitrile; N-[3-(2-cyano-5-imidazol-I -ylmethyl-phenoxy)-phenyl]- acetamide; 4-imidazol- 1-ylmethyl-2-(9-oxo-9H-fluoren-4-yloxy)-benzonitrile; 3-(2-cyano- 5-imidazol-1I-ylmethyl-phenoxy)-Nphenyl-*benzamide; 3-(2-cyano-5-imidazol-1I-ylmethyl- phenoxy)-N-ethyl-N-phenyl-benzamide; 3 -(2-cyano-5 -imidazol- 1-ylmethyl-phenoxy)-N- cyclopropylmethyl-N-phenyl-benzamide; 2-(5-chloro-pyridin-3-yloxy)-4-imidazol- 1 ylmethyl-benzonitrile; N-[3-(2-cyano-5-imidazol-1I-ylmethyl-phenoxy)-phenyl]- benzenesulfonamide; 4-imidazol- 1-ylmethyl-2-(indan-5-yloxy)-benzonitrile; 3-(9H- carbazol-2-yloxy)-4-imidazol- 1 -ylmethyl-benzonitrile; 4-imidazol- 1 -ylmethyl-2-(5,6,7,8- tetrahydro-naphthalen-2-yloxy)-benzonitrile; 4-imidazol- I -ylmethyl-2-(2-methoxy-4- propenyl-phenoxy)-benzonitrile; 4-imidazol- 1-ylmethyl-2-[4-(3-oxo-butyl)-phenoxy]- benzonitrile; 2-(3-chlorophenoxy)-5-imidazol- 1-ylmethyl-benzonitrile; 2-(4- chlorophenoxy)-4-imidazol- 1-ylmethyl-benzonitrile; 2-(3 ,5-dichlorophenoxy)-4-imidazol- I -ylmethyl-benzonitrile; 2-(pyridin-3-yloxy)-4-imidazol- 1-ylmethyl-benzonitrile; 2-(2- chilorophenoxy)-4- im idazol -I -ylmethyl-benzonitri le; 2-(3-chlorophenoxy)-5-(4-phenyl- imidazol- 1 -ylmethyl)-benzonitrile; 2-(biphen-2-yloxy)-4-imidazol- 1 -ylmethyl-benzonitrile; 2-(phenoxy)-4-imidazol- 1 -ylmethyl-benzonitrile; 2-(2-chloro-4-methoxyphenoxy)-4- imidazol- 1 -ylmethyl-benzonitrile; 2-(2-chlorophenylsulfanyl)-4-imidazol- 1 -ylmethyl- benzonitrile; 4-imidazol- 1-ylmethyl-2-(naphthalen-2-ylsulfanyl)-benzonitrile; 2-(2,4- dichlorophenylsulfanyl)-4-imidazol- 1-ylmethyl-benzonitrile; 2-(2,4-dichloro- benzenesulfinyl)-4-imidazol-1I-ylmethyl1-benzonitrile; 2-(2,4-dichloro-benzenesulfonyl)-4- imidazol- 1 -ylmethyl-benzonitrile; 2-(2-methyl-pyridin-3-yloxy)-4-imidazol- 1 -ylmethyl- benzonitrile; 2-(2,4-dimethyl-pyridin-3-yloxy)-4-imidazol- 1-ylmethyl-benzonitrile; 2-(4- chloro-2-methoxyphenoxy)-4-imidazol-1I -ylmethyl-benzonitrile; 2-(2-chlorophenoxy)-4-(5- 450 methyl-imidazol- 1-ylmethyl)-benzonitrile; 2-(2-chlorophenoxy)-4-(4-methyl-imidazol- 1- ylmethyl)-benzonitrile; 2-(3-chloro-5-trifluoromethyl-pyridin-2-yloxy)-4-imidazol- 1- C) 00 benzonitrile; N-[3-(2-cyano-5-imidazol- 1-ylmethyl-phenoxy)-phenyl]-benzamide; cyano-5 -imidazol- 1 -ylmethyl-phenoxy)-phenyl]-N-phenyl-acetamide; 4-imidazol- 1 ylmethyl-2-(quinolin-6-yloxy)-benzonitrile; 4-imidazol- 1-ylmethyi-2-(2-oxo- 1,2-dihydro- quinolin-6-yloxy)-benzonitrile; N-[3-(2-cyano-5-imidazol- 1-ylmethyl-phenoxy)-phenyl]-2- phenyl-acetamide; 5-(2-cyano-5-imidazol-1I-ylmethyl-phenoxy)-N-cyclohexyl- INDnicotinamide; N-(3-chloro-phenyl)-5-(2-cyano-5-imidazol-1I-ylmethyl-phenoxy)- C) 10 nicotinamide; 2-(2,3-dimethoxyphenoxy)-4-(2,4-dimethyl-imidazol- I -ylmethyl)- benzonitrile; 4-(2-methyl-imidazol- 1-ylmethyl)-2-(naphthalen-2-yloxy)-benzonitrile; 1- imidazol- l-yI-l -methyl-ethyl)-2-(naphthalen-2-yloxy)-benzonitrile; 1 -[4-iodo-3- (naphthalen-2-yloxy)-benzyl] -1H-imidazole; acetic acid 3 -(2-chloro-phcnoxy)-4-cyano- benzyl]-3 H-imidazol-4-ylmethyl ester; 2-(2-chloro-phenoxy)-4-(5-hydroxymethyl- imidazol- 1 -ylmethyl)-benzonitrile; 4-(5-aminomethyl-imidazol- 1 -ylmethyl)-2-(2-chloro- phenoxy)-benzonitrile; N- {3-[4-cyano-3-(2,3-dimethoxy-phenoxy)-benzyl]-3 H-imidazol-4- ylmethyl }-2-cyclohexyl-acetamide; 2-(3 -chiloro-phenoxy)-4- [(4-chloro-phenyl)- imidazol- 1 yl-methyl]-benzonitrile; 2-(3-chloro-phenoxy)-4-[ I-(4-chloro-phenyl)-2-hydroxy- 1- i midazolI- 1 -yl -ethyl] -benzonitri le; 2-(3-chloro-phenoxy)-4-[(4-chloro-phenyl)-hydroxy-(3 H- imidazol-4-yI)-methyl]-benzonitrile; 2-(2,4-dichloro-phenylsulfanyl)-4-[5-(2-morpholin-4- yl-ethyl)-imidazol-1I-ylmethyl]-benzonitrile; 2-(2,4-dichloro-phenoxy)-4-[5-(2-morpholin-4- yl-ethyl)-imidazol- 1-ylmethyl]-benzonitrile; 4-[hydroxy-(3-methyl-3 H-imidazol-4-yl)- methyl]-2-(naphthalen-2-yloxy)-benzonitrile; 4-[amino-(3-methyl-3 H-imidazol-4-yl)- methyl] -2-(naphthalen-2-yloxy)-benzonitri le; 4-[1I -hydroxy- 1 -methyl-3 H-imidazol-4-yl)- ethyl] -2-(naphthalen-2-yloxy)-benzonitrile; 4-[l 1-amino- I -(3-methyl-3 H-imidazol-4-yl)- ethyl] -2-(naphthalen-2 -yloxy)-benzonitri le hydrochloride; 3- 2-cyano-5-[ 1-amino-i1 methyl-3H-imidazol-4-yl)-ethyl]-phenoxy} -N-ethyl-N-phenyl-benzamide; 3- {2-cyano-5-[I hydroxy- I-(3-methyl-3 H-imidazol-4-yl)-ethyl]-phenoxy} -N-ethyl-N-phenyl-benzamide; 4- [I -hydroxy-lI-(3-methyl-3H-imidazol-4-yl)-ethyl]-2-(3-phenylamino-phenoxy)-benzonitrile; 1-hydroxy-l1-(3-methyl-3 H-imidazol-4-yl)-ethyl]-2-(3-phenoxy-phenoxy)-benzonitrile; 2-(3 -benzoyi-phenoxy)-4-[I1 -hydroxy- 1 -methyl -3H- imidazo I-4-yi) -ethyl] -benzonitri le; 2- (3-tert-butyl-phenoxy)-4- [1-hydroxy-l1-(3 -methyl-3H-imidazol-4-yl)-ethyl] -benzonitrile; 2- (3-diethylamino-phenoxy)-4-[ I-hydroxy-l1-(3-methyl-3H-imidazol-4-yl)-ethyl]- benzonitrile; 2-(5-chloro-2-oxo-2H-[1I,2']bipyridinyl-5 '-ylmethoxy)-4-imidazol-1I-ylmethyl- IeNDtie -mdzl ylehl2[-2oo2-yii- y)peoy-ezntie __ezorie 4-Imidazol- -ylmethyl-2-[-(2-oxo-2H- pyridin- -yl)-phenoxy]-benzonitrile;dz- 4-mdzl ymtyl2[-2oo2-prdi-I.)-hnx]bnzntie -mdzl o 1I -ylrnethyl-2-[4-(2-oxo-2H- pyridin- I -yl)-phenoxy]-benzonitrile; 4-imidazol- I -ylmethyl- 002[C2oopprdn y)peoy-ezoirl;4iiao-1-lehl2[-2oo 2[-o-piperidin- -yl)-phenoxy] -benzonitrile; 4-imidazol- -ylmethyl-2-[[-3-mty-2-oxo- 5piperidin-1I-yl)-phenoxy]-benzonitrile; 4-imidazol- 1-ylmethyl-2-[(3-mrphl-4-yl- phenoxy)-benzonitrile; 4-imidazol-1I-ylmethyl-2-(3 -piperidin-1I-ylmethyl-phenoxy)- benzonitrile; 2-[2-(3,3-dimethyl-2-oxo-piperidin- 1-yl)-phenoxy] -4-imidazol- 1-ylmethyl- IND benzonitrile; 2-[3-(3-ethyl- 1 -methyl-2-oxo-azepan-3-yl)-phenoxy]-4-imidazol- 1 -ylmethyl- benzonitrile; 2- [3 -ethyl- I -methyl-2-oxo-azepan-3 -yl)-phenoxy]-4-(2-methyl-imidazol- 1 yl)methyl-benzonitrile; 2- [3 -ethyl- I -methyl-2-oxo-azepan-3 imidazol- 1-yl)methyl-benzonitrile; 2- [3 -ethyl- I -methyl-2-oxo-azepan-3 -yl)-phenoxy] -4- (2,5-dimethyl-imidazol-1I-yI)methyl-benzonitrile; 2- [3 -ethyl- 1 -methyl-2-oxo-azepan-3 yl)-phenoxy]-4-[ 1,2,4]triazol-4-ylmethyl-benzonitrile; 2-[3-(3-ethyl- I-methyl-2-oxo- azepan-3-yl)-phenoxy]-4-[ 1,2,4]triazol-1I-ylmethyl-benzonitrile; 4-imidazol-1I-ylmethyl-2- I -methyl-2-oxo-azepan-3-yl)-phenoxy]-benzonitrile; 4-imidazol- 1 -ylmethyl-2-[3-( I- methyl-2-oxo-azocan-3-yl)-phenoxy]-benzonitrile; 4-imidazol- 1-ylmethyl-2-[3 -(1-methyl- 2-oxo-piperidin-3-yl)-phenoxy]-benzonitrile; 4-imidazol- 1 -ylmethyl-2- [3 -ethyl- 1 methyl-2-oxo-piperidin-3-yI)-phenoxy] -benzonitrile; 4-imidazol- 1-ylmethyl-2-[3-(2-oxo- azepan-3-yl)-phenoxy]-benzonitrile; 2-[3-(3-hydroxymethyl-lI-methyl-2-oxo-azepan-3 -yl)- phenoxyl-4-imidazol-1I-ylmethyl-benzonitrile; 2-[3-(3-cyclopropylmethyl-l1-methyl-2-oxo- azepan-3 -yl)-phenoxy] -4-imidazol-1I-ylmethyl-benzonitrile; 2-[4-bromo-3-(3- cyclopropylmethyl-l1-methyl-2-oxo-azepan-3-yl)-phenoxy]-4-imidazol-1I-ylmethyl- benzonitrile; 2-[3-(3-methoxymethyl-l1-methyl-2-oxo-azepan-3-yl)-phenoxy]-4-imidazol- 1- ylmethyl-benzonitrile; 2- [3-(3-ethyl-2-oxo-azepan-3-yl)-phenoxy]-4-imidazol- 1-ylmethyl- benzonitrile; 2-[3-(3-ethyl-azepan-3-yl)-phenoxy]-4-imidazol-1I-ylmethyl-benzonitrile; 2-[3- (1 -acetyl-3 -ethyl-azepan-3 -yl)-phenoxy]-4-imidazol-1I-ylmethyl-benzonitrile; 3 1 -ylmethyl-phenoxy)-phenyl]-3-ethyl-azepane- 1 -carboxylic acid-tert- butyl ester; 4- [5 -(2-amino-ethyl)-2-methyl-imidazol- 1 -ylmethyl] [3 -ethyl- I -methyl-2- oxo-azepan-3-yl)-phenoxy]-benzonitrile; 2-[3-(3-ethyl-lI-methyl-2-oxo-azepan-3-yl)- phenoxy]-4-[2-methyl-5-(2-morpholin-4-yl-ethyl)-imidazol- I -ylmethyl]-benzonitrile; N-[2- {4-cyano-3-[3-(3 -ethyl- I -methyl-2-oxo-azepan-3-yl)-phenoxy]-benzy I -2-methyl-3 H- imidazol-4-yl)-ethyl]-acetamide; 3-ethyl-3-[3-(3-imidazol-1I-ylmethyl-phenoxy)-phenyl]- 1- methyl-azepan-2-one; 2-[3-(3-ethyl-l1-methyl-2-oxo-azepan-3-yl)-phenoxy]-4-(3-methyl-3 452 INDdzl4ymty)bezntie (-ehli-ehl2ooazpn3-l-hnx] __4H-imidazol-4-ylmethyl)-benzonitrile; 2- [3 -ethyl- I -methyl-2-oxo-azepan-3 -yi)-hnx] 4-3-mdz04ymty)bnoirl;2[-3ehllmty--x-zpn3y) o phenoxy]-4-[hydroxy-(3-methyl-3-H-imidazol-4-yI)-methyl]-benzonitrile; 4-[amino-(3- 00 methyl H -imidazoi1-4-yl)-methyl [3 -ethyl-I1 -methyl-2-oxo-azepan-3 -yl)-phenoxy] benzonitrile; 2-[3 -ethyl- 1 -methyl-2-oxo-azepan-3-yI)-benzyl] -methyl-3 H- imidazoie-4-carbonyl)-benzonitrile; 2-[3 -(3-ethyl- I -methyl-2-oxo-azepan-3 -yl)-phenoxy] -4- (hydroxy-pyridin-3 -yl-methyl)-benzonitri le; 2- [3-(3-ethyl- 1 -methyl-2-oxo-azepan-3 -yl)- phenoxy]-4-pyridin-3-ylmethyl-benzonitrile; 2-[3-(3-ethyl-l1-methyl-2-oxo-azepan-3 IND phenoxy]-4-pyridin-2-ylmethyl-benzonitrile; 2-[3 -ethyl- 1 -methyl-2-oxo-azepan-3-yI)- phenoxy] 1-hydroxy-l1-(3-methyl-3H-imidazol-4-yl)-ethyl]-benzonitrile; 2-[3 -(3-ethyl-i- methyi-2-oxo-azepan-3-yl)-phenoxy]-4-[ 1-amino- I -(3-methyl-3H-imidazol-4-yl)-ethyl]- benzonitrile; 1 I-(4'-Cyanobenzyl) imidazol-5-ylmethyl]-4-[ 1-phenyl- 1- cyclopentylcarbonyl]piperazine; 1-ri -(4'-Cyanobenzyl) imidazol-5-ylmethyl]-4- [Cyclohexylphenyiacetyl]piperazine; I-[i -(4'-Cyanobenzyl).imidazol-5-ylmethyl]-4-[ 1-(3- methoxyphenyl)-l1-cyclopentylcarbonyl]piperazine; I-ri -(4'-Cyanobenzyl) ylmethyl]-4-[ 1-(3-phenoxyphenyl)-l1-cyclopentylcarbonyl]piperazine; i-[i -(4'-Cyano-3- fluorobenzyl) imidazol-5 -yimethyi] 1-(3-hydroxyphenyl)-1I- cyclohexylcarbonyllpiperazine; 1 -(4'-Cyanobenzyl) imidazol-5-yimethyl]piperazine-4- carboxylic acid-(2,6-dimethoxy)benzyl ester; 1-[i1 -(4'-Cyanobenzyl) ylmethyl]piperazine-4-(DL-2-hydroxy-2-(o-methoxyphenyl)) acetamide; 1 1 Cyanobenzyl) imidazol-5-ylmethyl]-4-[ 1-(2,6-dimethylbenzyioxycarbonyljpiperazine; 1-[i (4'-Cyanobenzyl) imidazol-5-ylmethyi] -4-ri -(2-methoxyphenyl)- 1- cyclopentylcarbonyl]piperazine; i-ri -(4'-Cyanobenzyl) imidazol-5-ylmethyl]-4-r 1- (bicyclo[3.1 .O]hex-3-yl)- I-(3-methoxyphenyl)-carbonyi]piperazine; (RJS) 2 [4- ((Phenyl)methyloxycarbonyl- I -piperazine)]-2-[ 1-(4'-cyanobenzyl)-2-methyl-5- imidazol]acetonitrile; i-ri -(4'-methylbenzyl) imidazol-5-ylmethyl]-4-[ 1-(2,6- dimethylbenzyloxycarbonyl]piperazine; 1 -(4'-Cyanobenzyl) ylmethyl] piperazine-4-carboxylic acid-(4-nitro)phenyl ester; 1 -(4-Cyanobenzyl) imidazol-5-ylmethyl]-4-[3-(4-fluorophenyl)-3-(tricyclo[3 .3.1 .13 7 ]dec-2-yl)- propionyljpiperazine; 1-(4'-cyanobenzyl)imidazol-5-yl-2-[4-(phenylmethyloxy carbonyl)piperazin- 1-yl]acetamide; 1 -(4'-cyanobenzyl) imidazol-5-ylmethyl]-4-[ 1-(2- i-ri -(4'-cyanobenzyl) ylmethyi] -4-ri -(pentafluororobenzyloxycarbonyl]piperazine; 1-[I '-cyanobenzyl) imidazol-5-ylmethyl]-4-[ 1-(2-ethoxybenzyloxycarbonyljpiperazine; 1-ri -(4'-cyanobenzyi) imidazol-5-ylmethyl]-4- 1-[(2-methoxypyridin-3 -yl)methyloxycarbonyl] }piperazine; 1 (4'-cyanobenzyl) imidazol-5-ylmethyl]-4-[1-(2- otrifluoromethoxybenzyloxycarbonyl]piperazine; 1- '-cyanobenzyl) 00 ylmethyl]-4-[ 1-(2,3-methylenedioxybenzyloxycarbonyl]piperazine- 1 -(4'-Cyanobenzyl) imidazol-5-ylmethyl]piperazine-4-carboxylic acid benzyl ester; 14[1 -(4'-Cyanobenzyl) -ylmethyl]-piperazine-3 -carboxylic acid-4-carboxylic acid benzyl ester; 1 Cyanobenzyl) imidazol-5-ylmethyl]-3 -methyl carboxy-piperazine-4-carboxyl ic acid, or a stereoisomeric form, or a pharmaceutically acceptable acid or base addition salt form thereof, in a therapeutically effective amount.
269. 321. The method according to claim 320, wherein the compound is selected from: I1- (3 -Chlorophenyl)-4- [1I-(4-cyanobenzyl)- 5-i midazolylmethyl]I-2-piperazi none; 1 Chlorophenyl)-4-[ 1-(4-cyanobenzyl)-5-imidazolylmethyl]-5-[2-(ethanesulfonyl)methyl]-2- piperazinone; I-(5-Chloro-2-oxo-2H-[ 1 ,2']bipyridinyl-5 '-ylmethyl)- I H-pyrrol-2-ylmethyl]- benzonitrile and 1 I -(4:-cyanobenzyl)-5-imidazolylmethyl)-N-(4-cyanobenzyl)amino] -4- (phenoxy)benzene or a stereoisomeric form, or a pharmaceutically acceptable acid or base addition salt form thereof, in a therapeutically effective amount.
270. 322. The method of treating a synucleinopathic subject, the method comprising, administering to a synucleinopathic subject a farnesyl transferase inhibitor compound selected from the compounds listed in US Pat No. 5,919,785 and US Pat No. 5,859,012 or a stereoisomeric form, or a pharmaceutically acceptable acid or base addition salt form thereof, in a therapeutically effective amount.
271. 323. he method of treating a synucleinopathic subject, the method comprising, administering to a synucleinopathic subject a farnesyl transferase inhibitor compound of the formula: 454 0 Cl O o N 0 N (N 0 N or a stereoisomeric form, or a pharmaceutically acceptable acid or base addition salt form thereof, in a therapeutically effective amount.
272. 324. The method of any of the preceding claims, wherein the synucleinopathic subject has a synucleinopathy selected from the group consisting of: Parkinson's disease, diffuse Lewy body disease, and multiple system atrophy disorder.
273. 325. The method of claim 321, wherein the subject is a human.
274. 326. The method of claim 322, wherein the effective amount comprises about of body weight to about 1000mg/kg of body weight at a frequency of administration from once a day to once a month.
275. 327. The method of claim 323, further comprising administering to the subject an amount of one or more non-farnesyl transferase inhibitor compounds effective to treat a neurological disorder.
276. 328. The method of claim 324, wherein each non-farnesyl transferase inhibitor compound is selected from the group consisting of: dopamine agonist, DOPA decarboxylase inhibitor, dopamine precursor, monoamine oxidase blocker, cathechol 0-methyl transferase inhibitor, anticholinergic, and NMDA antagonist. 455 ID S329. The method of claim 324, wherein each non-famesyl trasferase inhibitor compound is selected from the group consisting of Memantine, Aricept, and other O acetylcholinesterase inhibitors. 00
277. 330. An article of manufacture comprising packaging material and a farnesyl transferase inhibitor compound of any of the previous claims, wherein the article of manufacture further comprises a label or package insert indicating that the farnesyl transferase inhibitor compound can be administered to a subject for treating a synucleinopathy. (N 0 10 331. The article of manufacture of claim 327, wherein the synucleinopathy is selected from the group consisting of: Parkinson's disease, diffuse Lewy body disease, and multiple system atrophy disorder.
278. 332. The article of manufacture of claim 327, further comprising one or more non- farnesyl transferase inhibitor compounds effective to treat a neurological disorder.
279. 333. The article of manufacture of claim 327, wherein each non-famesyl transferase inhibitor compound is selected from the group consisting of: dopamine agonist, DOPA decarboxylase inhibitor, dopamine precursor, monoamine oxidase blocker, cathechol 0-methyl transferase inhibitor, anticholinergic, and NMDA antagonist.
280. 334. A method of treating a synucleinopathic subject, the method comprising, administering to a synucleinopathic subject a farnesyl transferase inhibitor in a therapeutically effective amount.
281. 335. The use of a farnesyl transferase inhibitor for the manufacture of medicament for treating a synucleinopathic subject. Date: 18 October 2006