AU2012203082A1 - Diaryl-purine, azapurines and -deazapurines as non-nucleoside reverse transcriptase inhibitors for treatment of HIV - Google Patents

Abstract

C-\NRPorbi)CC GS('V1 4M67_ I IOC.-2'/0(/2(12 This application concerns certain 2-phenylamino-6-aryl amino-. 6-aryloxy-. and 6- arylthio purines, -azapurincs and -dcasapurines. These compounds are non-nucICloside reverse 5 transcriptase inhibitors and have potential as anti-HIV treatment.

Description

AUSTRALIA PATENTS ACT 1990 DIVISIONAL APPLICATION NAME OF APPLICANT(S): Ardea Biosciences, Inc. ADDRESS FOR SERVICE: DAVIES COLLISON CAVE Patent Attorneys I Nicholson Street Melbourne, 3000 INVENTION TITLE: Diaryl-purine, azapurines and -deazapurines as non-nucleoside reverse transcriptase inhibitors for treatment of IIIV The following statement is a full description of this invention, including the best method of performing it known to us: (\NR'orbI\Ifl \SCG1317~R I D IO( - h 1//1 CVNR1'onblD( C G\CO II K I - )12 I)IARYL-P'URINES, -AZAIPURINIES AND -DEAZAPURINES AS NON-NUCLEO)SIDE REVERSE TRANSCRIPTASE INHIBITORS FOR TREATMENT OF HIIV 5 Cross-reference to Related Applications This is a divisional of Australian Patent Application No. 2006244195, the entire contents of which are incorporated herein by reference. This application claims priority to U.S. Provisional Application Scr. No. 60/678,667. filed May 5. 2005. the entirety of which is incorporated herein by reference. 10 Field of the Invention This application concerns certain 2-phenylamino-6-aryl amino-. 6-aryloxy-. and 6 arylthio- purines. -azapurines and -deazapurines. These compounds are non-nucIcleoside reverse transcriptase inhibitors and have potential as anti-I-lV treatment. Background of the Invention 15 Human Immunodeficiency Virus (I-IIV) presents a public-health and social catastrophe too well known to require documentation. One therapeutic approach to I1V has been inhibition of the viral RNA-dependent RNA polymerase; this enzyme is frequently referred to as "reverse transcriptase", abbreviated "RT". The first RT inhibitors were nucleoside analogs such as AZT and ddl. Although such nucleoside RT inhibitors were frequently effective 20 against the wild-type virus, any single-drug treatment has been hobbled by the virus's ability to readily produce drug-resistant mutants. This has led to an intense search for non-nucleoside RT inhibitors ("NNRTIs") which are both effective and capable of retaining their effectiveness despite drug-resistance mutations. A recent review of NNRTls can be found Balzarni..1.. 2004. Cur. Top. Med. Chem. 4. 921-44 (Erratum ibid. 4, I825). 25 Four leading NNRTI are: I) Efavirenz (4S)-6-chloro-4-(cyclopropylcthynyl)-l.4 dihydro-4-(trifluoromethyl)-21--3. I -benzoxazin-2-one; 2) Capravirine: Il--Imidazole-2 methanol, 5-((3,5-dichlorophenyl)thio)-4-( I -methylethyl)-I-(4-pyridinylmethyl)-carbamate (ester); 3) Etravirine ('TMC 125): 4-((6-amino-5-bromo-2-((4-cyanophenyl)amino)-4 pyrimidinyl)oxy)-3,5-dimethyl-benzonitrile; and 4) Rilpivirine (TMC-278): 4-([4-[(4-[(/E)-2 30 cyanoethenyl]-2,6-diniethylphenyl)amino]-2-pyrimidinyl)amino Ibenzonitrile. Rilpivirine and Etravirine belong to a subclass of NNRTIs called diarylpyrmidines ("DAPY"). For a review of these DAPY NNRTIs see Ludovici. D.W.. ef al, 2002, Bioorg. Med. Chem. Let.

WO 2006/122003 PCT/US2006/017677 2 11, 2235-9. An extensive patent literature also exists for DAPY. U.S. Patent No. 6,197,779; WO 00/27850; WO 2003/016306; and WO 2004/069812, all assigned to Janssen Pharmaceuticals. Diaryl compounds similar to Etravirine and Rilpivirine where the pyrimidine moiety 5 is replaced by a purine are described in WO 2005/028479, which also is assigned to Janssen. Brief Description of the Invention The invention provides a compound of formula I T Ar B N N H 10 where the dashed line represents a double bond that may be located either between A and B or between B and D, where A is -N=, N(Z) or C(Z); B is CH or =N-; D is CW or =N-, or N(W); 15 T is NH, O or S; Z is H, F, Cl, Br, CH 3 , CH 2 CHa, cyclopropyl, or benzyl, in which the phenyl moiety of the benzyl group is optionally substituted with methyl or methoxy, provided that Z is not F or Cl when A is NZ; W is H, F, Cl, Br, methyl, ethyl, cyclopropyl, allyl, CH 2

CF

3 , cyanomethyl, cyanoethyl, 20 CH=CHCN, or benzyl, in which the phenyl moiety of the benzyl group is optionally substituted with one or two groups selected independently from methoxy and methyl, provided that W is not F or Cl when D is NW; V is F, Cl, CN, SO 2

CH

3 , SO 2

NH

2 , SO 2

NHCH

3 , C=CCH 3 , or CH=CHCN; provided that when D is CW, A is not CZ and further provided that when neither A nor D is 25 CZ or CW, then B is CH; and Ar is selected from (a), (b), (c), and (d) below: WO 2006/122003 PCT/US2006/017677 3 - Q, (a) R 6 - -- R4 Q R 4 (b) R'~ R5 R 5 RP RP 1R 4 (C) R -R7 (d) R6-- | - R5 RP R8 R11 R9 Rio wherein each RP is selected from among methyl, ethyl, propyl, isopropyl, cyclopropylmethyl, or C3.C6 cycloalkyl, cyano, CH=CHCN, C1, Br, I, acetyl and alkylamino; R4, R5, and each R 5 are independently selected from among H, F, C1, Br, CH3, CF3, CH2F, CHF2, isopropyl, cyclopropyl, OCH3, OH, OCF3, NH2 and NHCH3, or R6 and RP on adjacent ring atoms, together with the ring atoms to which they are attached, form an additional fused five membered ring; Q and Q' are independently selected from N and CH; R7 is Cl, Br, I, CH3, CF3, OCH3, isopropyl, cyclopropyl, t-butyl, or cyclobutyl; and R8 - R" are, independently, H 10 or CH43. Compounds of formula I have inhibitory activity against both wild-type and mutated forms of human immunodeficiency virus type I (HIV-1). 15 WO 2006/122003 PCT/US2006/017677 4 Detailed Description of the Invention In one embodiment this invention provides a compound of formula IA, in which the 6-linker T of formula I is T', which may be 0 or S. 5 Ar A N N H IA When T of formula I or T of formula IA is 0, the invention excludes 1) compounds where 10 both RP and V are CH=CHCN or cyano unless at least one of A or D is neither -N= nor NH- and 2) compounds where a) R is CH=CHCN, cyano, or methyl; b) V is cyano or CH=CHCN; and c) A and D are both one of -N= ; N-benzyl or N-(substituted benzyl). In one subgeneric embodiment, the invention provides a compound of formula IA 15 where Ar is selected from 4-cyclopropyl phenyl; 4-cyclopropylmethyl phenyl; 4 bromophenyl; 4 -cyclopropyl-naphth-1 -yl; 2 ,6-dimethyl-4-cyanophenyl; 2,6-dimethoxy-4 cyanophenyl; 2 ,6-dimethyl-4-(2-cyanoethenyl) phenyl; 2,6-dimethoxy-4-(2-cyanoethenyl) phenyl; 2-methyl-4-cyclopropyl phenyl; 2,6-dimethyl-4-cyclopropyl phenyl; 2,6-di trifluoromethyl-4-cyclopropyl phenyl; 2,4,6-trimethyl phenyl; and 2,6-dimethyl-4-acetyl 20 phenyl. In another subgeneric embodiment, the invention contemplates a compound of formula IA where Ar is selected from the following: 5-cyclopropyl-8-quinolyl; 5-isopropyl-8 quinolyl; 5-cyano-8-quinolyl; 5-cyclopropyl-7-trifluoromethyl-8-quinolyl; 5-acetyl-8 25 quinolyl; 5-cyano- 7 -methoxy-8-quinolyl; 5-cyano-7-methyl-8-quinolyl; 5-cyclopropyl-7 trifluoromethoxy-8-isoquinolyl; 5-cyano-8-isoquinolyl; 5-cyano-7-methoxy-8-isoquinolyl; 5 cyano-7-methyl-8-isoquinolyl; 5-cyclobutyl-7-difluoromethyl-8-isoquinoly; 5,7-dimethyl-8 cinnolyl; 5-cyclopropyl-7-methyl-8-cinnolyl; and 5-(2-cyanoethenyl)-7-methyl-8-cinnolyl. 30 In another subgeneric embodiment, the invention provides a compound of formula

IA-I

WO 2006/122003 PCT/US2006/017677 5 Ar O' WN NN z IA-1 where Ar, V, W, and Z are defined as for formula I. 5 In another subgeneric embodiment, the invention provides a compound of formula IA-2 Ar O W N N N H Z 10 IA-2 where Ar, V, W, and Z are defined as for formula I. In another subgeneric embodiment, the invention provides a compound of formula IA-3 15 Ar W I -N N ~ / 'N V z IA-3 where Ar, V, W, and Z are defined as for formula I. 20 In another subgeneric embodiment, this invention provides a compound of formula IA-4 Ar O N INN N/ 25 z IA-4 WO 2006/122003 PCT/US2006/017677 6 where Ar, V, W, and Z are defined as for formula I. In another subgeneric embodiment, this invention provides a compound of formula 5 IA-5 Ar 0 'N -N N IA-5 10 where Ar, V, W, and Z are defined as for formula I. In another subgeneric embodiment, this invention provides a compound of formula IA-6 15 Ar N N / N/ V IA-6 where Ar, V, W, and Z are defined as for formula I. 20 In another subgeneric embodiment, this invention provides a compound of formula IA-7 Ar Ws IA-7 25 where Ar, V, W, and Z are defined as for formula I. In another subgeneric embodiment, this invention provides a compound of formula IA-8 WO 2006/122003 PCT/US2006/O17677 7 Ar S W -N N V /NI N>H--& Z IA-8 where Ar, V, W, and Z are defined as for formula I. 5 In another subgeneric embodiment, this invention provides a compound of formula IA-9 Ar S W N N NN~ N 10 IA-9 where Ar, V, W, and Z are defined as for formula I. In another subgeneric embodiment, this invention provides a compound of formula 15 IA-10 Ar S NN IA-10 where Ar, V, W, and Z are defined as for formula I. 20 In another embodiment, this invention provides a compound of formula IB HN'Ar B N H IB where all substituents are as described above, except that when Ar is (c), this invention 25 excludes compounds in which V is either cyano or CH=CHCN, unless A or D is CZ or CW.

WO 2006/122003 PCT/US2006/017677 8 In one subgeneric embodiment, the invention provides a compound of formula IB where Ar is (c), subject to the exclusion in the immediately preceding paragraph. In a more specific subgeneric embodiment, the invention provides a compound of formula IB where Ar is R 6

R

7 5 P where RP is CN, CH=CHCN, or cyclopropyl; where R 6 and R 7 are either both methyl or both methoxy; and subject to the exclusion described above for formula IB. In another subgeneric embodiment, this invention provides a compound of formula IB-1. Ar HN' W N/ N HV 10 Z IB-1 In another subgeneric embodiment, this invention provides a compound of formula IB-2. Ar HN Ws --- N /N V z 15 IB-2 where Ar, V, W, and Z are as described above for formula IB. In another subgeneric embodiment, the invention provides a compound of formula IB-3.

WO 2006/122003 PCT/US2006/017677 9 Ar HN -N W N V N IB-3 where Ar, W, and Z are as described above for formula IB. In another subgeneric embodiment, the invention provides a compound of formula IB-4. Ar HN' -N - N/ V N 5 Z IB-4 where Ar, V, and Z are as described above for formula IB. In more specific embodiments, the invention provides compounds of any of IA-1, IA 2, IA-3, IA-4, IA-5, IA-6, IA-7, IA-8, IA-9, IA-10, IB-1, IB-2, IB-3, and IB-4, where 10 Ar is (a). In additional more specific embodiments, the invention provides compounds of any of IA-1, IA-2, IA-3, IA-4, IA-5, IA-6, IA-7, IA-8, IA-9, IA-10, IB-1, IB-2, IB-3, and IB-4, where Ar is (b). In additional more specific embodiments, the invention provides compounds of any of 15 IA-1, IA-2, IA-3, IA-4, IA-5, IA-6, IA-7, IA-8, IA-9, IA-10, IB-1, IB-2, IB-3, and IB-4, where Ar is (c). In additional more specific embodiments, the invention provides compounds of any of IA-1, IA-2, IA-3, IA-4, IA-5, IA-6, IA-7, IA-8, IA-9, IA-10, IB-1, IB-2, IB-3, and IB-4, where Ar is (d). 20 In a more specific subgeneric embodiment, this invention provides or contemplates a compound of formula IA-7, IA-8, IA-9, or IA-10, where Ar is 4-cyclopropyl-, 4-acetyl-, 4 methyl-, 4-bromo-, or 4-cyano-2,6-di-substituted phenyl.

WO 2006/122003 PCT/US2006/017677 10 In another more specific subgeneric embodiment, this invention provides or contemplates a compound of formula IA-1, IA-2, IA-3, or IA-4, where Ar is 4 -cyclopropyl-, 4-acetyl-, 4-methyl-, 4-bromo-, or 4-cyano-2,6-di-substituted phenyl. In another more specific subgeneric embodiment, this invention provides or 5 contemplates a compound of formula IA-5 or IA-6, where Ar is 4-cyclopropyl-, 4-acetyl-, 4 methyl-, 4-bromo-or 4-cyano-2,6-di-subsituted phenyl. Synthetic procedures Compounds of this invention which are of the 7-deaza-8-azapurine type can be prepared according to Scheme 1. Scheme 1 NH 2 N-NH NNH N-NH /C H, l H O N

-

H O N C Ho N SH H (1) (2) (3) N-NH NVNH K r; CC N ONN NC- -OH cH NACN~ Podl IN HO cN (5) (4) 10 Compound (1), 2 -mercapto-6-hydroxy-7-deaza-8-aza-purine, can be synthesized by published procedures known to those skilled in the art. Youssif, S., et al., 2003, Bull. Kor. Chen. Soc., 24, 1429-32; Bontems, R.J., et al, 1990, J. Med. Chem. 33, 2174-8; Badger, G.M., & Rao, R.P., 1965, Aust. J. Chein. 18, 1267-71. 15 Alternatively, the 7-deaza-8-azapurines can be synthesized according to Scheme 2, where "PMBCI" is p-methoxy benzyl chloride. The starting material is prepared by published procedures known to those skilled in the art. Seela, F., 1999, Helv. Chim. Act. 82, 105-124; Taylor, E., 1992, Tetrahedron 48, 8089-100; Seela, F., 1986, Helv. Chim. Act. 69, 1602-1613.

WO 2006/122003 PCT/US2006/017677 11 Scheme 2 N-NH N-N PMB N N N PMBOI C N -N CN cI N2 NH 2 Pd(OAc) 2 CN N N (2) (3) N-NH IN5NPMB N FCN SN CN TFA 0N N4 CN N (5) (4) The 8-aza-9-deazapurines of this invention can be synthesized according to Scheme 3. The synthesis of the starting material was described by Lewis, A.F., & Townsend, L.B., 1982, J. Am. Chem. Soc. 104, 1073-78. Scheme 3 N N HO N POCl 3 C N PMBCI PMB' NH O NN 2 l N NH 2 Cl NNH H (1) (2) (3) N N HN N ZCN PMB- N CN -N H H OH 'M N TFA H HMBN CN CN (Pd(OA) 2 5 (6) (5) WO 2006/122003 PUSTU2006/01l7677 12 The 9-deazapurines of this invention can be synthesized by Scheme 4. The synthesis of the starting material is described by Kielich, Klaus, ed., "Synthetic Communications" 2002 vol. 32, pp-3 7 9 7

-

3802 . Scheme 4 HN HN

NH

2 POC CI HN NH 2 PMBClPMB N NH 2 (1) (2) (3) H N C N P M B N P C N ~ I 0 AN ~i OH PMN 0 ~ 0 N~ C.. H TFA CHNA CN CN H Pd(OAc) 2 CN (6) CN (5) (4) 5 The 7-deazapurines of this invention are prepared by the procedure of Scheme 5. The starting material can be synthesized by the condensation of 2,6-diamino-1,2 dihydro[3H]pyrimidin-4-one with chloroacetaldehyde followed by treatment with phosphorus oxychloride, as indicated in Examples I and 3. Scheme 5

NH

2 -n ,Bn / N HN N t-butylnitrite N A C N NH2 TFA, CF 3

CH

2 OH, 1000C 2 HF-pyndine (2) (3) / NH Bn ~N(NH -N~ TFA HN NNH N NH 2 N CN CF 3

CH

2 OH H AICl 3 H 0(4) 10 C:\NRPorb\DCC\SCG\407O082_. DOC 12/23/2011 - 13 The purine compounds of this invention can be synthesized by strategies similar to those provided above, using N 7 -benzyl-2,6-dichloropurine as the starting material. This procedure is illustrated in WO 2005/028479. 5 The reference in this specification to any prior publication (or information derived from it). or to any matter which is known, is not, and should not be taken as an acknowledgment or admission or any form of suggestion that that prior publication (or information derived from it) or known matter forms part of the common general knowledge in the field of endeavour to which this specification relates. 10 Throughout this specification and the claims which follow, unless the context requires otherwise, the word "comprise", and variations such as "comprises" and "comprising", will be understood to imply the inclusion of a stated integer or step or group of integers or steps but not the exclusion of any other integer or step or group of 15 integers or steps. Example I N. 1,. C * 20 Step Al: cl1 NaOIc H + HN CHO NH . o ' NH2 C \NRP rbI\DCC\SCG\407DO0?-1DOC-12/23/2011 - 13a 2-Amino-3,7-dihydro-pyrrolo(2,3-dIpyrim idin- 4 -one. To a mixture of 2,4-diamino-6 hydroxypyrimidine (20.0 g, 159 mmol) and NaOAc (26.0 g, 317 mmol) in H20 (300 mL) at 65 0 C was added a solution of chloroacetaldehyde (22.0 mL, 50% in H 2 0, 173 rnmol) in

H

2 0 (22 mL) dropwise for 90 min. The mixture was stirred at 65 0 C for an additional 2 h 5 and cooled to room temperature. The reaction mixture was concentrated in vacuo to one third of its original volume and stored at 4 0 C for 16 h. The light pink precipitates were filtered, washed with an ice cold H 2 0 (5 mL), and dried under high vacuum for 16 h. The precipitates were placed in Soxhlet extractor and refluxed with methanol (200 mL) for 24 h. The methanol was concentrated to give 13.3 g (56%) of 2-amino-3,7-dihydro 10 pyrrolo[2,3-d]pyrimidin- 4 -one as a light pink solid.

WO 2006/122003 PCT/US2006/017677 14 Step A2: NH NH N POCI - N

NH

2 C1 N NH 2 5 4-Chloro-7H-pyrrolo(2,3-dlpyrimidin-2-ylamine. To a solution of 2-amino-3,7-dihydro pyrrolo[2,3-d]pyrimidin-4-one (5.00 g, 33.3 mmol), dimethylaniline (4.22 mL, 41.0 mrnol) and benzyltriethylamnimonium chloride (15.2 g, 66.6 mmol) in acetonitrile (25 mL) at room temperature under argon was added POC1 3 (18.6 mL, 200 mmol) dropwise for 30 min. The mixture was refluxed at 85'C for 3 h and cooled to room temperature. The reaction was 10 concentrated in vacuo to brown oil and to the oil was added an ice cold H20 (10 mL). The pH of the solution was adjusted to 5 by the addition of an aqueous NH 4 0H solution. Silica gel chromatography (CH 2

CI

2 :MeOH = 95: 5) yielded 2.53 g (45%) of 4-chloro-7H pyrrolo[2,3-dlpyrimidin-2-ylamine as a light yellow solid. The product was then benzylated at N 7 using standard techniques. 15 Step C: OH Bn NN Bn ZN N 0 NJ NH 2 Ci N NH 2 NaH, NMP 7-benzyl-4-(2,4,6-trimethyl-phenoxy)-7H-pyrrolo2,3-dpyrimidin-2-ylamine. To a solution of 2,4,6-trimethylphenol (161 mg, 1.16 mmol) in 1-methyl-2-pyrridone (2 mL) in a 20 sealed tube was added NaH (46 mg, 1.16 mmol). The reaction mixture was stirred at room temperature for 15 min and a solution of 7-benzyl-4-chloro-7H-pyrrolo[2,3-d]pyrimidin-2 ylamine (100 mg, 0.39 mmol) in 1 -methyl-2-pyrridone (1 mL) was added to the mixture. The mixture was heated at 150 *C for 16 h and cooled to room temperature. The reaction mixture was poured into ice water and extracted with EtOAc (2 x 20 mL). The combined organic 25 solution was washed with H20 (20 mL) and brine (20 mL), dried with Na 2

SO

4 , and WO 2006/122003 PCT/US2006/017677 15 concentrated to dryness. Silica gel chromatography (Hexanes:EtOAc = 75:25) yielded 107 mg (77%) of 7-benzyl-4-(2,4,6-trimethyl-phenoxy)-7H-pyrrolo[2,3-d]pyrimidin-2-ylamine. Step D: Bn N' Bn N HF-pyr N O N NH2 t-butylnitrite ' N F 0N 5 7-benzyl-2-fluoro-4-(2,4,6-trimethyl-phenoxy)-7H-pyrrolo[2,3-dipyrimidine. To 7 benzyl-4-(2,4,6-trimethyl-phenoxy)-7H-pyrrolo[2,3-d]pyrimidin-2-ylamine (105 mg, 0.29 mmol) in a polyethylene flask at -50 *C under argon was added 60% HF in pyridine (12 mL). To the resulting solution tert-butylnitrite (0.052 mL, 0.44 mmol) was added dropwise for 5 10 min. The reaction was warmed to -40 *C and stirred for 30 min at the temperature. The reaction mixture was diluted with CHC1 3 (100 mL) and poured into K 2 C0 3 (3 g) in a beaker. Ice water (50 mL) was carefully added to the mixture. The CHCl 3 layer was separated, washed with aqueous NaHCO 3 solution (20 mL) and brine (20 mL), dried with Na 2

SO

4 , and concentrated to dryness. Silica gel chromatography (Hexanes:EtOAc = 75:25) yielded 72 mg 15 (68%) of 7 -benzyl-2-fluoro-4-(2,4,6-trimethyl-phenoxy)-7H-pyrrolo[2,3-d]pyrimidine as a light yellow solid. Step E: ,Bn Bn O N H 2 N CN O N NaH, NMP 0 N H\ O 20 4

-[

7 -benzyl- 4 -(2,4,6-trimethyl-phenoxy)-7H-pyrrolo[2,3-d]pyrimidin-2-ylamino] benzonitrile. To a solution of 4-aminobenzonitrile (101 mg, 0.86 mmol) in 1-methyl-2 pyrridone (1 mL) was added NaH (34 mg, 0.86 mmol). The reaction mixture was stirred at WO 2006/122003 PCT/US2006/017677 16 room temperature for 15 min and a solution of 7 -benzyl-2-fluoro-4-(2,4,6-trimethyl phenoxy)-7H-pyrrolo[2,3-d]pyrimidine (62 mg, 0.17 mmol) in 1-methyl-2-pyrridone (1 mL) was added to the mixture. The mixture was stirred at room temperature for 1 h, poured into ice water, and extracted with EtOAc (2 x 20 mL). The combined organic solution was 5 washed with H 2 0 (20 mL) and brine (20 mL), dried with Na 2

SO

4 , and concentrated to dryness. Silica gel chromatography (Hexanes:EtOAc = 75:25) yielded 64 mg (82%) of 4-[7 benzyl4-(2,4,6-trimethyl-phenoxy)-7H-pyrrolo[2,3-d]pyrimidin-2-ylamino]-benzonitrile. Step F: NBn H ZNN O N CN A. N CN 0ON HCNJ13 1,2-dichlorobenzene 10 4

-[

4

-(

2

,

4 ,6-Trimethyl-phenoxy)-7H-pyrrolo[ 2

,

3 -dlpyrimidin-2-ylamino]-benzonitrile. To a solution of 4-[7-benzyl-4-(2,4,6-trimethyl-phenoxy)-7H-pyrrolo[2,3-d]pyrimidin-2 ylamino]-benzonitrile (38 mg, 0.083 mmol) in 1,2-dichlorobenzene (1 mL) was added aluminum chloride (55 mg, 0.42 mmol). The reaction mixture was stirred at 160 'C for 4 h and cooled to room temperature. The mixture was poured into ice water and extracted with 15 CH 2

CI

2 (2 x 10 mL). The combined organic solution was washed with brine (10 mL), dried with Na 2

SO

4 , and concentrated to dryness. Silica gel chromatography (Hexanes:EtOAc = 50:50) yielded 15 mg (49%) of 4

-[

4

-(

2

,

4

,

6 -trimethyl-phenoxy)-7H-pyrrolo[2,3-d]pyrimidin 2-ylamino]-benzonitrile as a tan solid. 20 WO 2006/122003 PCT/US2006/017677 17 Example 2 SH Bn N Bn / N'Bn N t-butylnitrite N JN S NZS N F NaH S N NH 2 HF-pyridine C1 N NH 2 NMP 77% 94% (a) (b)

NH

2 (c) NaH CN RT 83% 1h Bn CN N yCN S~ N C ON AICl1 CN S. NIa SN NNHSN Nr H 1,2-dichlorobenzene 40% (d) 5 Step A: SH-B NBn N N S N NH 2 Cl N NH 2 NMP 94% 7-benzyl-4-(2,4,6-trimethyl-phenylsulfanyl)-7H-pyrrolo[2,3-dlpyrimidin-2-ylamine. To a solution of 2,4,6-trimethylbenzene-1-thiol (231 mg, 1.52 mmol) in 1-methyl-2-pyrridone (2 10 mL) was added NaH (58 mg, 1.52 mmol). The reaction mixture was stirred at room temperature for 15 min and a solution of 7-benzyl-4-chloro-7H-pyrrolo[2,3-d)pyrimidin-2 ylamine (131 mg, 0.51 mmol) in 1-methyl-2-pyrridone (2 mL) was added to the mixture. The mixture was heated at 60 *C for 16 h and cooled to room temperature. The reaction was poured into ice water and extracted with EtOAc (2 x 20 mL). The combined organic solution WO 2006/122003 PCT/US2006/017677 18 was washed with H20 (20 mL) and brine (20 mL), dried with Na 2

SO

4 , and concentrated to dryness. Silica gel chromatography (Hexanes:EtOAc = 75:25) yielded 180 mg (94%) of 7 benzyl-4-(2,4,6-trimethyl-phenylsulfanyl)-7H-pyrrolo[2,3-d]pyrimidin-2-ylamine. Step B: B n Bn S NH t-butylnitrite S N NH 2 HF-pyridine S N F 77% 5 7 -benzyl-2-fluoro-4-(2,4,6-trimethyl-phenylsulfanyl)-7H-pyrrolo[2,3-dpyrimidine. To 7 -benzyl- 4

-(

2

,

4

,

6 -trimethyl-phenylsulfanyl)-7H-pyrrolo[2,3-d]pyrimidin-2-ylamine (155 mg, 0.41 mmol) in a polyethylene flask at -50 *C under argon was added 60% HF in pyridine (12 mL). To the solution was added tert-butylnitrite (0.074 mL, 0.62 mmol) dropwise for 5 min. 10 The reaction was warmed to -40 *C and stirred for 30 min at the temperature. The reaction was diluted with CHC1 3 (100 mL) and poured into K 2 C0 3 (3 g) in a beaker. To the mixture was carefully added ice water (50 mL). The CHC1 3 layer was separated, washed with aqueous NaHCO 3 solution (20 mL) and brine (20 mL), dried with Na 2

SO

4 , and concentrated to dryness. Silica gel chromatography (Hexanes:EtOAc = 75:25) yielded 118 mg (77%) of 7 15 benzyl- 2 -fluoro- 4

-(

2 ,4,6-trimethyl-phenylsulfanyl)-7H-pyrrolo[2,3-d]pyrimidine as a yellow solid. Step C: NBn Bn ~~CN S N F NaH 83% S N N CN H - RT

H

2 N-QCN T N 4

-[

7 -benzyl- 4 -(2, 4

,

6 -trimethyl-phenylsulfanyl)-7H-pyrrolo[ 2 ,3-dJpyrimidin-2-ylamino] 20 benzonitrile. To a solution of 4-aminobenzonitrile (184 mg, 1.56 mmol) in 1 -methyl-2 pyrridone (2 mL) was added NaH (62 mg, 1.56 mmol). The reaction mixture was stirred at room temperature for 15 min and a solution of 7-benzyl-2-fluoro-4-(2,4,6-trimetbyl phenylsulfanyl)-7H-pyrrolo[2,3-d]pyrimidine (118 mg, 0.31 mmol) in l-methyl-2-pyrridone (2 mL) was added to the mixture. The mixture was stirred at room temperature for 4 h, then WO 2006/122003 PCT/US2006/017677 19 poured into ice water and extracted with EtOAc (2 x 20 mL). The combined organic solution was washed with H 2 0 (20 mL) and brine (20 mL), dried with Na 2

SO

4 , and concentrated to dryness. Silica gel chromatography (Hexanes:EtOAc = 75:25) yielded 123 mg (83%) of 4 [7-benzyl-4-(2,4,6-trimethyl-phenylsulfanyl)-7H-pyrrolo[2,3-d]pyrimidin-2-ylamino] 5 benzonitrile. Step D: N'A NH N C N CN H AIC1 3 H 1,2-dichlorobenzene 40% 4-[4-(2,4,6-Trimethyl-phenylsulfanyl)-7H-pyrrolo[2,3-d]pyrimidin-2-ylamino] benzonitrile. To a solution of 4 -[7-benzyl-4-(2,4,6-trimethyl-phenylsulfanyl)-7H 10 pyrrolo[2,3-d]pyrimidin-2-ylamino]-benzonitrile (103 mg, 0.21 mmol) in 1,2 dichlorobenzene (2 mL) was added aluminum chloride (87 mg, 0.65 mmol). The reaction mixture was stirred at 160 *C for 1.5 h and cooled to room temperature. The mixture was poured into ice water and extracted with CH 2

CI

2 (2 x 10 mL). The combined organic solution was washed with brine (10 mL), dried with Na 2

SO

4 , and concentrated to dryness. 15 Silica gel chromatography (Hexanes:EtOAc = 50:50) yielded 28 mg (34%) of 4-[4-(2,4,6 trimethyl-phenylsulfanyl)-7H-pyrrolo[2,3-d]pyrimidin-2-ylamino]-benzonitrile as a tan solid.

WO 2006/122003 PCT/US2006/017677 20 Example 3 OH Bn NaOAc N C1 + HN H20 BnBr Et 4 NBr CNNH pock I N NC- 2 yH N Ho H 2 N NH 2 P CN NH2 NaOH CI N NH2 NaH, NMP (a) (b) (c) CN (d) HF-pyr H t-butylnitrite N Bn Bn CN AICl3 H 2 N- CN 1,2-dichlorobenzene 0 H -- -- '''''-O-N-F -j NaH, NMP 0 N (0) (e) CN 5 Steps A and B as in Example 1. Step C: OH Bn ,Bn ZN N B 0 NH2 C NH 2 NaH, NMP CN 10 4-(2-Amino-7-benzyl-7H-pyrrolo[2,3-dlpyrimidin-4-yloxy)-3,5-dimethyl-benzonitrile. To a solution of 4-hydroxy-3,5-dimethylbenzonitrile (1.62 mg, 11.0 mmol) in 1-methyl-2 pyrridone (5 mL) in a sealed tube was added NaH (441 mg, 11.0 mmol). The reaction mixture was stirred at room temperature for 15 min and a solution of 7-benzyl-4-chloro-7H pyrrolo[2,3-d]pyrimidin-2-ylamine (950 mg, 3.67 mmol) in 1-methyl-2-pyrridone (5 mL) was 15 added to the mixture. The mixture was heated at 150 *C for 16 h and cooled to room temperature. The reaction was poured into ice water and extracted with EtOAc (2 x 50 mL). The combined organic solution was washed with H 2 0 (50 mL) and brine (50 mL), dried with Na 2

SO

4 , and concentrated to dryness. Silica gel chromatography (Hexanes:EtOAc = 75:25) WO 2006/122003 PCT/US2006/017677 21 5 yielded 1.12 mg (83%) of 4-(2-amino-7-benzyl-7H-pyrrolo[2,3-d]pyrimidin-4-yloxy)-3,5 dimethyl-benzonitrile. Step D: Bn N' Bn N N N 7N NH2 HF-pyr F t-butylnitrite O N CN CN 4-(7-benzyl-2-fluoro-7H-pyrrolo[2,3-dlpyrimidin-4-yloxy)-3,5-dimethyl-benzonitrile. To 10 4-(2-amino-7-benzyl-7H-pyrrolo[2,3-d]pyrimidin-4-yloxy)-3,5-dimethyl-benzonitrile (70 mg, 0.19 mmol) in a polyethylene flask at -50 *C under argon was added 60% HF in pyridine (12 mL). To the solution was added tert-butylnitrite (0.068 mL, 0.57 mmol) dropwise for 5 min. The reaction was warmed to -40 *C and stirred for 30 min at the temperature. The reaction was diluted with CHC1 3 (100 mL) and poured into K 2 C0 3 (3 g) in a beaker. To the mixture 15 was carefully added ice water (50 mL). The CHC1 3 layer was separated, washed with aqueous NaHCO 3 solution (20 mL) and brine (20 mL), dried with Na 2

SO

4 , and concentrated to dryness. Silica gel chromatography (Hexanes:EtOAc = 75:25) yielded 36 mg (51%) of 4 (7-benzyl-2-fluoro-7H-pyrrolo[2,3-d]pyrimidin-4-yloxy)-3,5-dimethyl-benzonitrile.

WO 2006/122003 PCT/US2006/017677 22 Step E: NBn ,Bn ZNN F H 2 N CN NC O1N F .-- - ---------- _ O H NaH, NMP CN CN 4-[7-benzyl-2-(4-cyano-phenylamino)-7H-pyrrolo[2,3-d pyrimidin-4-yloxy]-3,5 dimethyl-benzonitrile. To a solution of 4-aminobenzonitrile (54 mg, 0.46 mmol) in 1 5 methyl-2-pyrridone (1 mL) was added NaH (18 mg, 0.46 mmol). The reaction mixture was stirred at room temperature for 15 min and a solution of 4-(7-benzyl-2-fluoro-7H-pyrrolo[2,3 d]pyrimidin-4-yloxy)-3,5-dimethyl-benzonitrile (34 mg, 0.091 mmol) in 1-methyl-2 pyrridone (1 mL) was added to the mixture. The mixture was stirred at room temperature for 1 h, poured into ice water, and extracted with EtOAc (2 x 20 mL). The combined organic 10 solution was washed with H20 (20 mL) and brine (20 mL), dried with Na2SO4, and concentrated to dryness. Silica gel chromatography (Hexanes:EtOAc = 75:25) yielded 28 mg (65%) of 4-[7-benzyl-2-(4-cyano-phenylamino)-7H-pyrrolo[2,3-d]pyrimidin- 4 -yloxy]-3,5 dimethyl-benzonitrile. Step F: Bn N NCN O N CN - ON 0- N 7 H \a O AIC13 1,2-dichlorobenzene 15 ON CN 4-[2-(4-Cyano-phenylamino)-7H-pyrrolo[2,3-dpyrimidin-4-yloxy]-3,5-dimethyl benzonitrile. To a solution of 4-[7-benzyl-2-(4-cyano-phenylamino)-7H-pyrrolo[2,3 d]pyrimidin-4-yloxy]-3,5-dimethyl-benzonitrile (28 mg, 0.060 mmol) in 1,2-dichlorobenzene (1 mL) was added aluminum chloride (40 mg, 0.30 mmol). The reaction mixture was stirred 20 at 160 0C for 45 min and cooled to room temperature. The mixture was poured into ice water and extracted with CH 2

CI

2 (2 x 10 mL). The combined organic solution was washed with brine (10 mL), dried with Na 2 SO4, and concentrated to dryness. Silica gel chromatography WO 2006/122003 PCT/US2006/017677 23 (Hexanes:EtOAc = 50:50) yielded 6 mg (27%) of 4

-[

2

-(

4 -cyano-phenylamino)-7H pyrrolo[2,3-dlpyrimidin-4-yloxy]-3,5-dimethyl-benzonitrile as a tan solid. Example 4 5

NH

2 -Bn NBn N nN t-butylnitrite N HN N NH 2 HF-pyrdlne HN N F C N NH 2 (a) -30% (b)

NH

2 (c) CN NaH SNMP Bn H NcN CN - ----------------- HN N N OCN (d) Step A:

NH

2 -Bn / n N HN NINH 2 CI N H 2 10 7 -benzyl-N4-(2,4,6-trimethyl-phenyl)-7H-pyrrolo[2,3-dlpyrimidine-2,4-diamine. To a suspension of 7 -benzyl- 4 -chloro-7H-pyrrolo[2,3-d]pyrimidin-2-ylamine (200 mg, 0.78 mmol) and 2 ,4,6-trimethylaniline (0.44 mL, 3.08 mmol) in 2 ,2,2-trifluoroethanol (4 mL) was added trifluoroacetic acid (0.48 mL, 6.24 mmol). The resulting solution was heated at 100 *C 15 for 2 days and cooled to room temperature. The reaction was concentrated to brown oil and diluted with CH 2

CI

2 (30 mL). The organic solution was washed with aqueous NaHCO 3 WO 2006/122003 PCT/US2006/0 17677 24 solution (20 mL) and brine (20 mL), dried with Na 2

SO

4 , and concentrated to dryness. Silica gel chromatography (CH 2

C

2 :MeOH = 95:5) yielded 251 mg (90%) of 7-benzyl-N4-(2,4,6 trimethyl-phenyl)-7H-pyrrolo[2,3-d]pyrimidine-2,4-diamine. Step B: Bn - Bn HN N t-butylnitrite HN F

H

2 HF-pyridine -30% 5 (7-benzyl-2-fluoro-7H-pyrrolo[2,3-djpyrimidin-4-yl)-(2,4,6-trimethyl-phenyl)-amine. To 7-benzyl-N4-(2,4,6-trimethyl-phenyl)-7H-pyrrolo2,3-d]pyrimidine-2,4-diamine (251 mg, 0.70 mmol) in a polyethylene flask at -50 "C under argon was added 60% HF in pyridine (24 mL). To the solution was added tert-butylnitrite (0.42 mL, 3.5 mmol) dropwise for 10 min. 10 The reaction was warmed to -40 *C and stirred for 30 min at the temperature. The reaction was diluted with CHC1 3 (200 mL) and poured into K 2 C0 3 (6 g) in a beaker. To the mixture was carefully added ice water (100 mL). The CHCl 3 layer was separated, washed with aqueous NaHCO 3 solution (40 mL) and brine (40 mL), dried with Na 2

SO

4 , and concentrated to dryness. Silica gel chromatography (Hexanes:EtOAc = 75:25) yielded 56 mg (22%) of (7 15 benzyl-2-fluoro-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-(2,4,6-trimethyl-phenyl)-amine. Step C: Bn N Bn NaH -N yCN FM HN N N HN F H 2 N-QCN HH 20 4-[7-benzyl-4-(2,4,6-trimethyl-phenylamino)-7H-pyrrolo[2,3-dipyrimidin-2-ylaminol benzonitrile. To a suspension of (7-benzyl-2-fluoro-7H-pyrrolo[2,3-dlpyrimidin-4-yl) (2,4,6-trimethyl-phenyl)-amine (42 mg, 0.12 mmol) and 4-aminobenzonitrile (55 mg, 0.47 mmol) in 2,2,2-trifluoroethanol (4 mL) was added trifluoroacetic acid (0.072 mL, 0.94 mmol). The resulting solution was heated at 90 0C for 16 h, then cooled to room temperature.

WO 2006/122003 PCT/US2006/017677 25 The reaction was concentrated to produce a brown oil and diluted with CH 2 C1 2 (30 mL). The 5 organic solution was washed with H 2 0 (20 mL) and brine (20 mL), dried with Na 2

SO

4 , and concentrated to dryness. Silica gel chromatography (Hexanes:EtOAc = 75:25) yielded 34 mg (64%) of 4-[7-benzyl-4-(2,4,6-trimethyl-phenylamino)-7H-pyrrolo[2,3-d]pyrimidin-2 ylamino]-benzonitrile. Step D: NBn N NN H N N CN -N CN HN NAN---- N N Nlo H H 10 4-[4-(2,4,6-Trimethyl-phenylamino)-7H-pyrrolo[2,3-dlpyrimidin-2-ylamino] benzonitrile. To a solution of 4-[7-benzyl-4-(2,4,6-trimethyl-phenylamino)-7H-pyrrolo[2,3 d]pyrimidin-2-ylamino]-benzonitrile (34 mg, 0.074 mmol) in 1,2-dichlorobenzene (1 mL) was added aluminum chloride (50 mg, 0.37 mmol). The reaction mixture was stirred at 160 15 *C for 2 h and cooled to room temperature. The mixture was poured into ice water and extracted with CHC 3 (2 x 10 mL). The combined organic solution was washed with brine (10 mL), dried with Na 2

SO

4 , and concentrated to dryness. Silica gel chromatography

(CH

2 C1 2 :Acetone = 90:10) yielded 5 mg (19%) of 4-[4-(2,4,6-trimethyl-phenylamino)-7H pyrrolo[2,3-d]pyrimidin-2-ylamino]-benzonitrile as a tan solid. 20 25 WO 2006/122003 PCT/US2006/017677 26 Example 5 OH Bn Bn N nC N O N t- b u ty ln it rite O N "N NH 2 HF-pyridine Cl N NH 2 (a) (b) ON CN

NH

2 (c) NaH N NMP B n O N CN ANi CN H 1,2-dichlorobenzene (d) CN CN 5 Step A: OH Bn Bn N' ON N N NH 2 C N NH 2 CN 4-(2-Amino-7-benzyl-7H-pyrrolo[2,3-dlpyrimidin-4-yloxy)-3,5-dimethyl benzonitrile. To a solution of 4-hydroxy-3,5-dimethylbenzonitrile (1.62 mg, 11.0 mmol) in 10 1-methyl-2-pyrridone (5 mL) in a sealed tube was added NaH (441 mg, 11.0 mmol). The reaction mixture was stirred at room temperature for 15 min and a solution of 7-benzyl-4 chloro-7H-pyrrolo(2,3-d]pyrimidin-2-ylamine (950 mg, 3.67 mmol) in 1-methyl-2-pyrridone (5 mL) was added to the mixture. The mixture was heated at 150 *C for 16 h and cooled to WO 2006/122003 PCTIUS2006/017677 27 room temperature. The reaction was poured into ice water and extracted with EtOAc (2 x 50 mL). The combined organic solution was washed with H 2 0 (50 mL) and brine (50 mL), dried with Na 2

SO

4 , and concentrated to dryness. Silica gel chromatography (Hexanes:EtOAc = 75:25) yielded 1.12 mg (83%) of 4-(2-amino-7-benzyl-7H-pyrrolo[2,3-d]pyrimidin-4 5 yloxy)-3,5-dimethyl-benzonitrile. Step B: NBn Bn N t-butylnitrite O N 0 N NH 2 HF-pyridine 0 N'F CN CN 10 4-(7-benzyl-2-fluoro-7H-pyrrolo[2,3-dpyrimidin- 4 -yloxy)-3,5-dimethyl-benzonitrile. To 4

-(

2 -amino-7-benzyl-7H-pyrrolo[2,3-d]pyrimidin-4-yloxy)-3,5-dimethyl-benzonitrile (70 mg, 0.19 mmol) in a polyethylene flask at -50 *C under argon was added 60% HF in pyridine (12 mL). To the solution was added tert-butylnitrite (0.068 mL, 0.57 mmol) dropwise for 5 min. 15 The reaction was warmed to -40 *C and stirred for 30 min at the temperature. The reaction was then diluted with CHCl 3 (100 mL) and poured into K 2 C0 3 (3 g) in a beaker. Ice water (50 mL) was carefully added. The CHC1 3 layer was separated, washed with aqueous NaHCO 3 solution (20 mL) and brine (20 mL), dried with Na 2

SO

4 , and concentrated to dryness. Silica gel chromatography (Hexanes:EtOAc = 75:25) yielded 36 mg (51%) of 4-(7 20 benzyl- 2 -fluoro-7H-pyrrolo[2,3-d]pyrimidin-4-yloxy)-3,5-dimethyl-benzonitrile. Step C: N'Bn N ,Bn NaH NMP N CN O F H 2 N--CN N H CN CN WO 2006/122003 PCT/US2006/017677 28 4-[7-benzyl-2-(4-cyano-phenylamino)-7H-pyrrolo[2,3-dpyrimidin-4-yloxyl-3,5 dimethyl-benzonitrile. To a solution of 4-aminobenzonitrile (54 mg, 0.46 mmol) in 1 methyl-2-pyrridone (1 mL) was added NaH (18 mg, 0.46 mmol). The reaction mixture was stirred at room temperature for 15 min and a solution of 4-(7-benzyl-2-fluoro-7H-pyrrolo[2,3 5 d]pyrimidin-4-yloxy)-3,5-dimethyl-benzonitrile (34 mg, 0.091 mmol) in 1-methyl-2 pyrridone (1 mL) was added to the mixture. The mixture was stirred at room temperature for 1 h, poured into ice water and extracted with EtOAc (2 x 20 mL). The combined organic solution was washed with H 2 0 (20 mL) and brine (20 mL), dried with Na 2

SO

4 , and concentrated to dryness. Silica gel chromatography (Hexanes:EtOAc = 75:25) yielded 28 mg 10 (65%) of 4-[7-benzyl-2-(4-cyano-phenylamino)-7H-pyrrolo(2,3-d]pyrimidin-4-yloxy]-3,5 dimethyl-benzonitrile. Step D: NBn. N ~ -CN / N O N N<C N AIC13 O NCN H H H 1,2-dichlorobenzene CN CN 15 4-[2-(4-Cyano-phenylamino)-7H-pyrrolo[2,3-dpyrimidin-4-yloxy-3,5-dimethyl benzonitrile. To a solution of 4-[7-benzyl-2-(4-cyano-phenylamino)-7H-pyrrolo[2,3 d]pyrimidin-4-yloxy]-3,5-dimethyl-benzonitrile (28 mg, 0.060 mmol) in 1,2-dichlorobenzene (1 mL) was added aluminum chloride (40 mg, 0.30 mmol). The reaction mixture was stirred at 160 *C for 45 min and cooled to room temperature. The mixture was poured into ice water 20 and extracted with CH 2 Cl 2 (2 x 10 mL). The combined organic solution was washed with brine (10 mL), dried with Na 2

SO

4 , and concentrated to dryness. Silica gel chromatography (Hexanes:EtOAc =50:50) yielded 6 mg (27%) of 4-[2-(4-cyano-phenylamino)-7H pyrrolo[2,3-d]pyrimidin-4-yloxy]-3,5-dimethyl-benzonitrile as a tan solid. 25 WO 2006/122003 PCT/US2006/017677 29 Example 6 NH N H OTBS 1) ZnCI Pd(PPh) 4 OH N NH 2 N N CN 1) NaH o N KC N 2) TBAF 2) 4-NH 0 C0 Br C NC TFE Br CI N CI OH 5 4-Cyclopropyl-2,6-dimethylphenol. To a suspension of (4-bromo-2,6-dimethylphenoxy) tert-butyldimethylsilane (668 mg, 2.12 mmol) and tetrakis(triphenylphosphine)palladium (122 mg, 0.11 mmol) in THF (20 mL) was added cyclopropyl zinc chloride (28.0 mL, 11.2 mmol). The mixture was heated at 80"C for 24 h and cooled to room temperature. The 10 reaction was passed through a short pad of SiO 2 to remove the catalyst and the solution was concentrated to oil. The resulting oil was diluted in EtOAc (100 mL), washed with brine (100 mL), dried with Na 2

SO

4 , and concentrated to dryness. Silica gel chromatography (Hexanes:EtOAc = 90:10) yielded 370 mg (63%) of tert-butyl(4-cyclopropyl-2,6 dimethylphenoxy)dimethylsilane. To tert-butyl(4-cyclopropyl-2,6 15 dimethylphenoxy)dimethylsilane (320 mg, 1.16 mmol) in THF (10 mL) was added a solution of tetrabutylammonium fluoride (5.0 mL, 1 M in TIF, 5.0 mmol) and acetic acid (0.40 mL). The reaction was stirred at room temperature for 3 h and concentrated to dryness. Silica gel chromatography (Hexanes:EtOAc = 85:15) yielded 175 mg (93%) of 4-cyclopropyl-2,6 dimethylphenol as a light yellow oil. 20 NH N O l WO 2006/122003 PCT/US2006/017677 30 2 -chloro-6-(4-cyclopropyl-2,6-dimethylphenoxy)-9H-purine. To a solution of 4 cyclopropyl-2,6-dimethylphenol (263 mg, 1.62 mmol) in 1-methyl-2-pyrridone (3 mL) at 0*C was added NaH (65 mg, 1.62 mmol). The reaction mixture was stirred at room temperature for 30 min and a solution of 2,6-dichloropurine (102 mg, 0.54 mmol) in 1-methyl-2-pyrridone 5 (2 mL) was added to the mixture. The mixture was heated at 100*C for 16 h and then cooled to room temperature. The reaction was poured into ice water and extracted with CHC1 3 (3 x 20 mL). The combined organic solution was washed with H 2 0 (20 mL) and brine (20 mL), dried with Na 2

SO

4 , and concentrated to dryness. Silica gel chromatography (MeOH:CHCl 3 = 5:95) yielded 114 mg (67%) of 2 -chloro-6-(4-cyclopropyl-2,6-dimethylphenoxy)-9H-purine. 10 NNH o N CN H 4-(6-(4-cyclopropyl-2,6-dimethylphenoxy)-9H-purin-2-ylamino)benzonitrile. To a suspension of 2 -chloro-6-(4-cyclopropyl-2,6-dimethylphenoxy)-9H-purine (28 mg, 0.088 mmol) and 4-aminobenzonitrile (42 mg, 0.35 mmol) in 2,2,2-trifluoroethanol (3 mL) in a 15 sealed tube was added trifluoroacetic acid (0.056 mL, 0.70 mmol). The resulting solution was heated at 90 0 C for 3 days. The reaction was cooled to room temperature and concentrated to dryness. Silica gel chromatography (CH2Cl 2 :Acetone = 80:20) yielded 7 mg (20%) of 4-(6-(4-cyclopropyl-2,6-dimethylphenoxy)-9H-purin-2-ylamino)benzonitrile as a light yellow solid. 20 Example 7 OH NH NH 2 NH NH t-butylnitrite NH N SbC1 3 N 0 C ciN N H c7i N HiNc NaH .- TFA . C N NH2 C N CI H 25 WO 2006/122003 PCT/US2006/017677 31 NH NK CI N CI 2,4-dichloro-7H-pyrrolo[2,3-dlpyrimidine. To a suspension of 4-chloro-7H-pyrrolo[2,3 d]pyrimidin-2-ylamine (500 mg, 2.97 mmol) in 1,2-dichloroethane (40 mL) at -10*C under 5 argon was added antimony chloride (750 mg, 3.29 mmol). After stirring for 5 min, tert butylnitrite (2.50 mL, 20.8 mmol) was added to the solution. The reaction was stirred at -10*C for 3 h. The reaction was diluted with CHCl 3 (100 mL) and poured into ice water (50 mL). The CHCl 3 layer was separated, washed with brine (20 mL), dried with Na 2

SO

4 , and concentrated to dryness. Silica gel chromatography (Hexanes:EtOAc = 50:50) yielded 10 239 mg (43%) of 2,4-dichloro-7H-pyrrolo[2,3-d]pyrimidine as a tan solid. NH o N C1 2 -chloro-4-(4-cyclopropyl-2,6-dimethylphenoxy)-7H-pyrrolo{2,3-d]pyrimidine. To a solution of 4-cyclopropyl-2,6-dimethylphenol (259 mg, 1.60 mmol) in T-F (3 mL) at 0*C 15 was added NaH (64 mg, 1.60 mmol). The reaction mixture was stirred at room temperature for 30 min and a solution of 2,4-dichloro-7H-pyrrolo[2,3-d]pyrimidine (100 mg, 0.53 mmol) in THEF (2 mL) was added to the mixture. The mixture was heated at 80 0 C for 16 h and cooled to room temperature. The reaction was poured into ice water and extracted with CHC1 3 (3 x 20 mL). The combined organic solution was washed with H20 (20 mL) and brine 20 (20 mL), dried with Na 2

SO

4 , and concentrated to dryness. Silica gel chromatography (Hexanes:EtOAc = 75:25) yielded 79 mg (48%) of 2-chloro-4-(4-cyclopropyl-2,6 dimethylphenoxy)-7H-pyrrolo[2,3-d]pyrimidine as a tan solid.

WO 2006/122003 PCT/US2006/017677 32 / NH O N" N , CN H 4

-(

4

-(

4 -cyclopropyl-2,6-dimethylphenoxy)-7H-pyrrolo [2,3-d]pyrimidin-2 ylamino)benzonitrile. To a suspension of 2-chloro-4-(4-cyclopropyl-2,6-dimethylphenoxy) 7H-pyrrolo[2,3-d]pyrimidine (75 mg, 0.24 mmol) and 4-aminobenzonitrile (113 mg, 0.96 5 mmol) in 2,2,2-trifluoroethanol (4 mL) in a sealed tube was added trifluoroacetic acid (0.15 mL, 1.92 mmol). The resulting solution was heated at 90*C for 3 days. The reaction was diluted with EtOAc (50 mL), washed with NaHCO 3 (20 mL) and brine (20 mL), dried with Na 2

SO

4 , and concentrated to dryness. Silica gel chromatography (CH 2 C1 2 :Acetone = 90:10) yielded 15 mg (16%) of 4

-(

4

-(

4 -cyclopropyl-2,6-dimethylphenoxy)-7H-pyrrolo[2,3 10 d]pyrimidin-2-ylamino)benzonitrile as a tan solid. Example 8 15 Scheme I

H

2

SO

4 2 N N DMFOM N 1. DMF DMA II 0 NNH 2 HO o NH 2. BnBr 0 N 2. Na 2

S

2 0 4 o H Hn Bn N\ 1. 3M NaOH 2. Pd/C, NH 4

CO

2 Hj H N 0 NH 2 Scheme 1 illustrate the synthesis of 9-deazaguanine by starting with commercially available 2 -amino- 6 -methylpyrimidin-4(3H)-one and nitrated with nitric acid followed by 20 treatment of the nitrated product with NN-dimethylformamide dimethyl acetal (DMF-DMA) to afford the corresponding 2-(dimethylamino)methyleneimino derivative. It was then benzylated to produce 3 -benzyl- 2 -[(dimethylamino)methyleneimino]-5-nitro-6 methylpyrimidin-4-one by treating with benzyl bromide and converted to benzylated-2,6-bis dimethylaminomethylene derivative with DMF-DMA. Reductive cyclization with sodium WO 2006/122003 PCT/US2006/017677 33 hydrosulfite followed by de-protection with 3M NaOH and de-benzylation with Pd/C and

NH

4

CO

2 H afforded 9-deazaguanine. Scheme 2 HN>. Bn-N N SbCl 3 Bn-N N pathway 3 H N 0 N NH 2 POC3 C N NH 2 CI N Ci CI N CI H OH OH H pathway I pathway 2 NaH NaH NaH NC Bn-N Bn-O C HN C 0 NINH 2 0 NICI 0 N C 2N 2

~NH

2 0 N C HF-PyrT 1. TFA, ITA NC CN C 0 Bn OHCO H.NHN N Al F O 0 NIN HH NC .NaH, \/ N2 ~ . AIC 3 0 HN? CN 0 -NN'j H NC 5 Scheme 2 illustrates the 3 different pathways which provide the various substituted 9 deazapurines. Other products are synthesized by analogous methods, which a person skilled in the art could formulate, based on the reaction sequences given above. In certain cases, the person skilled in the art would see that protecting groups might be necessary. The synthetic 10 scheme can be summarized as follows. Benzylation of 9-deazaguanine followed by chlorination with POC1 3 gives the chlorinated 9-deazapurine product. This chlorinated intermediate can either be coupled with R2 (pathway 1) followed by diazotization with t-butyl nitrite; displaced with F; coupled with 15 R3 and de-benzylated to give the product; or it can undergo pathway 2, which is diazotization WO 2006/122003 PCT/US2006/017677 34 with t-butyl nitrite in the presence of antimony chloride followed by coupling with R2 and R3, followed by de-benzylation to afford the final product. Alternatively, pathway 3 provides for de-benzylation of the dichloro-9-deazapurine followed by the coupling with R2 and R3 respectively to provide the various substituted 9-deazapurine. 0 2 N 0 N NH 2 5 H 2-Amino-6-methyl-5-nitropyrimidin-4(3H)-one To a mixture of 2-amino-6-methylpyrimidin-4(3H)-one (50 g, 0.4 mol) in 250 mL of

H

2

SO

4 at 0 *C was added 40 mL of HN0 3 with an additional funnel. After being stirred at room temperature for 3 h, the reaction mixture was slowly poured into 3.6 L of diethyl ether 10 and stirred for 15 min. Decant the ether solution and added 1.0 L of ethyl acetate to the solid and stirred for 10 h. The solid (54.8 g, 81% yield) was filtered and used for next step without any further purification. 0 2 N N H \-N (E)-N,N-Dimethyl-N'-(4-methyl-5-nitro-6-oxo-1,6-dihydropyrimidin-2 15 yl)formimidamide To a suspension of 2-Amino-6-methyl-5-nitropyrimidin-4(3H)-one (54.8 g, 0.32 mol) in CH 2 Cl 2 (461 mL) was added DMF-dimethylacetal (103.1 mL, 0.77 mol) and stirred at room temperature for 1.5 h. The reaction mixture was filtered, washed with CH 2 Cl 2 , and used for the next step without further purification (31.9 g, 44% yield). 20 0 2 N / N O N N Bn N (E)-N'(1-benzyl-4-methyl-5-nitro-6-oxo-1,6-dihydropyrimidin-2-y)-N,N dimethylformimidamide To a suspension of (E)-NN-Dimethyl-N'-(4-methyl-5-nitro-6-oxo-1,6 25 dihydropyrimidin-2-yl)formimidamide (53.4 g, 0.24 mmol) in DMF (690 mL) was added DBU (44.6 mL, 0.30 mol) and benzyl bromide (44.4 mL, 0.29 mol) and stirred at room WO 2006/122003 PCT/US2006/017677 35 temperature for 1 h. The excess of DBU was neutralized with HCl, and the mixture was concentrated in vacuo. The residue was dissolved in methylene chloride and extracted twice with 2M HCI and water, then dried over Na 2

SO

4 and concentrated. Trituration with ethanol afforded the crystalline product which was washed with ethanol to give the product (64.7 g, 5 86% yield) and used in the next step without further purification.

N

0 2 N N ON N (E)-N'-(1-benzyl-4-((E)-2-(dimethylamino)vinyl)-5-nitro-6-oxo-1,6-dihydropyrimidin-2 yl)-N,N-dimethylformimidamide To a solution of (E)-N'(1 -benzyl-4-methyl-5-nitro-6-oxo- 1,6-dihydropyrimidin-2-yl) 10 NN-dimethylformimidamide (64.7 g, 0.2 mol) in DMF (254 mL) was added DMF dimethylacetal (54.5 mL, 0.41 mol). The reaction mixture was stirred for 3 h at 65 *C, cooled, and the solvent was removed under reduced pressure. The residue was triturated with ethanol, and the solid was collected by vacuum filtration (69.2 g, 91%) and used in the next step without further purification. H N ON BA N 15 \ (E)-N'-(3-benzyl-4-oxo-4,5-dihydro-3H-pyrrolo[3,2-d]pyrimidin-2-yI)-N,N . dimethylformimidamide To a mixture of (E)-N'-(1-benzyl-4-((E)-2-(dimethylamino)vinyl)-5-nitro-6-oxo-1,6 dihydropyrimidin-2-yl)-N,N-dimethylformimidamide (43.0 g, 0.12 mol) in THF (151 mL) 20 was added an aqueous saturated solution of Na 2

S

2 0 4 and stirred at room temperature overnight. Upon completion of the reaction, the solid was filtered and washed with THF to afford the product (21.2 g, 62% yield) which was used in the next step without further purification.

WO 2006/122003 PCT/US2006/017677 36 H N N N') NH2 Bn 2-Amino-3-benzyl-3H-pyrrolo[3,2-dlpyrimidin-4(51)-one To a mixture of (E)-N'-(3-benzyl-4-oxo-4,5-dihydro-3H-pyrrolo[3,2-d]pyrimidin-2 yl)-N,N-dimethylformimidamide (21.2 g, 0.07 mol) in MeOH (382 mL) was added 3M 5 NaOH (276 mL) and heated at 100 *C for 5 h. After completion of the reaction, the reaction mixture was cooled to 0 *C. The solid was filtered (15.8 g, 91%) and used in the next step without further purification. H N N

NH

2 H 2-Amino-3H-pyrrolo[3,2-dlpyrimidin-4(5H)-one 10 To a mixture of 2-amino-3-benzyl-3H-pyrrolo[3,2-d]pyrimidin-4(5H)-one (10 g, 0.04 mol) in MeOH (334 mL) was added 10% Pd/C (2 g), ammonium formate (13.2 g, 0.21 mmol) and heated at 75*C for 4 h. After completion of the reaction, the reaction mixture was cooled and filtered through a pad of Celite with hot 1:1 DMF/MeOH. The filtrate was concentrated in vacuo to provide the product as an off-white solid (6.2 g, 99%). 15 Bn-N N o N NH 2 H 2-Amino-5-benzyl-3H-pyrrolo[3,2-d]pyrimidin-4(5H)-one To a suspension of 2-amino-3H-pyrrolo[3,2-d]pyrimidin-4(5H)-one (336.7 mg, 2.0 mmol) in CH 2

C

2 (14.3 mL) was added benzyl bromide (0.26 mL, 2.2 mmol) and TBABr 20 (644 mg, 2.0 mmol). The reaction mixture was cooled to 0 *C, and to it was added 50% NaOH (1.7 mL). The resulting mixture was stirred for 2 h as it warmed from 0 *C to room temperature. Water was then added, and the solution was washed with CHCl 3 . The combined organic layers were washed with brine, dried over Na 2

SO

4 , filtered, and concentrated in vacuo. Purification by column chromatography, eluting with 25 CH 2 Cl 2 /Acetone (5:1-1:1), afforded the product as a tan solid (423 mg, 82%) WO 2006/122003 PCT/US2006/017677 37 Bn-N / N CI N NH 2 5-benzyl-4-chloro-5H-pyrrolo 3,2-djpyrimidin-2-amine A mixture of 2-amino-5-benzyl-3H-pyrrolo[3,2-d]pyrimidin-4(5H)-one (1.1 g, 7.4 mmol) and POC1 3 (7 mL, 74 mmol) was heated at 116 *C for 3 h. Upon completion of the 5 reaction, the reaction mixture was poured into ice and extracted three times with ethyl acetate. The combined organic layers were washed with brine, dried over Na 2

SO

4 , filtered, and concentrated in vacuo. Purification by column chromatography, eluting with

CH

2

CI

2 /Acetone (3:1), afforded the product as a white solid (490 mg, 40%). Bn-N / N 0 N NH 2 10 5-benzyl-4-(mesityloxy)-5H-pyrrolo[3,2-d]pyrimidin-2-amine To a stirred suspension of NaH (56 mg, 2.33 mmol) in dry NMP (2 mL) was added 2,4,6-trimethyl phenol (317 mg, 2.33 mmol). The mixture was stirred at room temperature for 30 min under argon. The reaction mixture was added to a solution of 5-benzyl-4-chloro-5H 15 pyrrolo[3,2-d]pyrimidin-2-amine (200 mg, 0.78 mmol) in dry NMP (1.5 mL) and the resulting solution was heated at 90 'C for 16 h. After completion of the reaction, the reaction mixture was diluted with water and washed with EtOAc. The combined organic layers were washed with water, 2% NaOH, and brine and dried over Na 2

SO

4 , filtered, and concentrated in vacuo. The crude product was purified by column chromatography, eluting 20 with hexanes/ethyl acetate (3:1) to give the product as a white solid (140 mg, 50%). Bn-N N O N F 5 -benzyl-2-fluoro-4-(mesityloxy)-5H-pyrrolo[3,2-dipyrimidine WO 2006/122003 PCT/US2006/017677 38 A solution of 5-benzyl-4-(mesityloxy)-5H-pyrrolo(3,2-d]pyrimidin-2-amine (139.9 mg, 0.39 mmol) in pyridine (1.6 mL) was cooled to -50 *C and HF-pyr (8 mL) and t-butyl nitrite (0.19 rmL, 1.56 mmol) was added dropwise. The reaction mixture was stirred at 50 "C to -30 *C for 1.5 h. Upon completion of the reaction, the reaction mixture was poured into 5 K 2 C0 3 (5 g), slowly added water and washed with CHC1 3 x 3. The combined organic layers were washed with brine, dried (Na 2

SO

4 ), filtered and concentrated in vacuo. The crude product was purified by silica gel column chromatography, eluting with hexanes/ethyl acetate (2:1) to give the product as a white solid (116 mg, 82%). Bn.-N N CN O N N H 10 4-(5-benzyl-4-(mesityloxy)-5H-pyrrolo [3,2-dlpyrimidin-2-ylamino)benzonitrile A stirred suspension of NaH (63.8 mg, 2.66 mmol) in dry NMP (1.5 mL) was added 4-aminobenzylnitrile (188 mg, 2.66 mmol) and stirred at room temperature for 30 min under argon. The reaction mixture was added to a solution of 5-benzyl-2-fluoro-4-(mesityloxy) 15 5H-pyrrolo[3,2-d]pyrimidine (115 ng, 0.32 mmol) in dry NMP (1.7 mL) and stirred at room temperature for 2 h. After completion of the reaction, the resulting mixture was diluted with water and washed with EtOAc 3 times. The combined organic layers were washed with water, NH 4 Cl, water x 2, and brine, dried over Na 2

SO

4 , filtered, and concentrated in vacuo. The crude product was purified by column chromatography, eluting with 1% MeOH:CH 2

CI

2 , 20 which afforded the product as a tan solid (120 mg, 80%). HN N CN O N N H 4-(4-(Mesityloxy)-5H-pyrrolo[3,2-djpyrimidin-2-ylamino)benzonitrile To a suspension of 4-(5-benzyl-4-(mesityloxy)-5H-pyrrolo[3,2-d]pyrimidin-2 ylamino)benzonitrile (150 mg, 0.33 mmol) in 1,2-dichlorobenzene (13 mL) was added AlCl 3 25 (436 mg, 3.27 mmol). The reaction mixture was heated at 160 *C for 1.5 h during which the WO 2006/122003 PCT/US2006/017677 39 reaction mixture became dark and homogeneous. Upon completion of the reaction, the reaction mixture was cooled and washed with NH 4 C. The combined organic layers were washed with brine, dried over Na 2

SO

4 , filtered, and concentrated in vacuo. The crude product was purified by column chromatography, eluting with Hexanes:Ethyl acetate (5:1 5 1:1) provided the product as a tan solid (27.8 mg, 23%). Example 9 Bn-N N o N NH 2 CN 10 4-(2-Amino-5-benzyl-5H-pyrrolo[3,2-dpyrimidin-4-yloxy)-3,5-dimethylbenzonitrile To a stirred suspension of NaH (155 mg, 6.47 mmol) in dry NMP (4 mL) was added 4-hydroxy-3,5-dimethylbenzonitrile (570 mg, 3.88 mmol), and the mixture was stirred at room temperature for 30 min under argon. The reaction mixture was added to a solution of 5 benzyl-4-chloro-5H-pyrrolo[3,2-d]pyrimidin-2-amine (400 mg, 1.55 mmol) in dry NMP (4 15 mL) and heated at 160 *C for 16 h. After completion of the reaction, the resulting mixture was diluted with water and washed with EtOAc. The combined organic layers were washed with water, 2% NaOH, brine, dried over Na 2

SO

4 , filtered, and concentrated in vacuo. The crude product was purified by column chromatography, eluting with hexanes/ethyl acetate (2:1-1:4) to give the product as a light yellow solid (342 mg, 60%). 20 Bn-N / N O N F CN 4-(5-benzyl-2-fluoro-5H-pyrrolo[3,2-dlpyrimidin-4-yloxy)-3,5-dimethylbenzonitrile A solution of 4-(2-amino-5-benzyl-5H-pyrrolo[3,2-d]pyrimidin-4-yloxy)-3,5 dimethylbenzonitrile (319.4 mg, 0.87 mmol) in pyridine (3 mL) was cooled to -50 *C and WO 2006/122003 PCT/US2006/017677 40 HF-pyr (15 mL) and t-butyl nitrite (0.42 mL, 3.46 mmol) were added dropwise. The reaction mixture was stirred at -50 *C to -20 *C for 1.5 h. Upon completion of the reaction, the mixture was poured into K 2 C0 3 (8 g), diluted with water and washed with CHC1 3 x 3. The combined organic layers were washed with brine, dried. (Na 2

SO

4 ), filtered, and concentrated 5 in vacuo. The crude product was purified by silica gel column chromatography, eluting with hexanes/ethyl acetate (2:1-1:1) which same the product as a light yellow solid (314 mg, 97%). Bn-N N CN O N N H CN 10 4-(5-benzyl-2-(4-cyanophenylamino)-5H-pyrrolo[3,2-d]pyrimidin-4-yloxy)-3,5 dimethylbenzonitrile To a stirred suspension of NaH (101 mg, 4.21 mmol) in dry NMP (4 mL) was added 4-aminobenzylnitrile (299 mg, 2.53 mmol) and stirred at room temperature for 30 min under argon. The reaction mixture was added to a solution of 4-(5-benzyl-2-fluoro-5H-pyrrolo[3,2 15 d]pyrimidin-4-yloxy)-3,5-dimethylbenzonitrile (314 mg, 0.84 mmol) in dry NMP (4.4 mL) and stirred at room temperature for 2 h. After completion of the reaction, the resulting mixture was diluted with water and washed with EtOAc x 3. The combined organic layers were washed with water, NH 4 CI, water x 2, brine, dried over Na 2

SO

4 , filtered, and concentrated in vacuo. The crude product was purified by column chromatography, eluting 20 with 1% MeOH:CH 2 Cl 2 , producing the product as a tan solid (320 mg, 80%). HN N CN O N N H CN 4-(2-(4-Cyanophenylamino)-5H-pyrrolo[3,2-d]pyrimidin-4-yloxy)-3,5 dimethylbenzonitrile WO 2006/122003 PCT/US2006/017677 41 To a suspension of 4-(5-benzyl-2-(4-cyanophenylamino)-5H-pyrrolo[3,2-d]pyrimidin 4-yloxy)-3,5-dimethylbenzonitrile (240 mg, 0.51 mnmol) in 1,2-dichlorobenzene (20 mL) was added AlCl 3 (681 mg, 5.1 mmol). The reaction mixture was heated at 160 *C for 1.5 h, during which time the reaction mixture became dark and homogeneous. Upon completion of 5 the reaction, the reaction mixture was cooled and washed with NH 4 C. The combined organic layers were washed with brine, dried over Na 2

SO

4 , filtered and concentrated in vacuo. The crude product was purified by preparative TLC TLC eluting with Hexanes:Ethyl acetate (2.5:1) and produced the product as a pink solid (51 mg, 26%). 10 Example 10 Bn-N N S N NH 2 5-benzyl-4-(mesitylthio)-5H-pyrrolo[3,2-d]pyrimidin-2-amine To a stirred suspension of NaH (48 mg, 2 mmol) in dry NMP (2 mL) was added 2,4,6 15 trimethyl-benzene-1-thiol (191 mg, 1.2 mmol) The mixture was and stirred at room temperature for 30 min under argon. The reaction mixture was then added to a solution of 5 benzyl-4-chloro-5H-pyrrolo[3,2-d]pyrimidin-2-amine (103 mg, 0.4 mmol) in dry NMP (2.5 mL) and heated at 60 *C for 16 h. After completion of the reaction, the resulting mixture was diluted with water and washed with EtOAc. The combined organic layers were washed with 20 water, 2% NaOH, and brine; dried over Na 2

SO

4 ; filtered; and concentrated in vacuo. The crude product was purified by column chromatography, eluting with hexanes/ethyl acetate (2:1-1:3) to give the product as a light yellow solid (131 mg, 88%). Bn-N / N S N F 5-benzyl-2-fluoro-4-(mesitylthio)-5H-pyrrolo[3,2-dpyrimidine WO 2006/122003 PCT/US2006/017677 42 A solution of 5-benzyl-4-(mesitylthio)-5H-pyrrolo[3,2-djpyrimidin-2-amine (131 mg, 0.35 mmol) in pyridine (1.6 mL) was cooled to -50 *C and added HF-pyr (8 mL) and t-butyl nitrite (0.17 mL, 1.4 mmol) dropwise. The reaction mixture was stirred at -50 "C to -40 "C for 1.5 h. Upon completion of the reaction, the reaction was poured into K 2 C0 3 (5 g), slowly 5 added water and washed with CHC1 3 x 3. The combined organic layers were washed with brine, dried (Na 2

SO

4 ), filtered and concentrated in vacuo. The crude product was purified by silica gel column chromatography, eluting with hexanes/ethyl acetate (5:1-1:1) to give the product as an off-white solid (94 mg, 71%). Bn-N N ON S N N H 10 4-(5-benzyl-4-(mesitylthio)-5H-pyrrolo[3,2-d]pyrimidin-2-ylamino)benzonitrile To a stirred suspension of NaH (30 mg, 1.25 mmol) in dry NMP (1.5 mL) was added 4-aminobenzylnitrile (87.4 mg, 0.74 mmol) and stirred at room temperature for 30 min under argon. The reaction mixture was added to a solution of 5-benzyl-2-fluoro-4-(mesitylthio) 15 5H-pyrrolo[3,2-d]pyrimidine (93 mg, 0.25 mmol) in dry NMP (1 mL) and stirred at room temperature for 2 h. After completion of the reaction, the resulting mixture was diluted with water and washed with EtOAc x 3. The combined organic layers were washed with water,

NH

4 Cl, water x 2, brine, dried over Na 2

SO

4 , filtered, and concentrated in vacuo. The crude product was purified by preparative TLC TLC, eluting with Hexanes:Ethyl acetate (1.5:1) 20 afforded the product as a tan solid (12.6 mg, 11%). HN N CN S N N' H 4

-(

4 -(mesitylthio)-5H-pyrrolo[3,2-dlpyrimidin-2-ylamino)benzonitrile To a suspension of 4-(5-benzyl-4-(mesitylthio)-5H-pyrrolo[3,2-d]pyrimidin-2 25 ylamino)benzonitrile (9.2 mg, 0.03 mmol) in 1,2-dichlorobenzene (1 mL) was added AiC1 3 WO 2006/122003 PCT/US2006/017677 43 (26 mg, 0.3 mmol). The reaction mixture was heated at 160 "C for 1.5 h, which the reaction mixture became dark and homogeneous. Upon completion of the reaction, the reaction mixture was cooled and washed with NH 4 CI. The combined organic layers were washed with brine, dried over Na 2

SO

4 , filtered, and concentrated in vacuo. The crude product was 5 purified by preparative TLC TLC, eluting with Hexanes:Ethyl acetate (2.5:1) produced the product as a pink solid (7.7 mg, 20%). Example 11 Bn-N / N 10 CI N CI 5-benzyl-2,4-dichloro-5H-pyrrolo[3,2-dpyrimidine To a suspension of 5-benzyl-4-chloro-5H-pyrrolo[3,2-d]pyrimidin-2-amine (641 mg, 2.5 mmol) in 1,2-dichloroethane (35 mL) was cooled to -10 *C SbCl 3 (850 mg, 3.7 mmol) was added. The reaction mixture was stirred for 5 min. t-butyl nitrite (2.1 mL, 17.4 mmol) 15 was added dropwise and the stirred mixture was from -10 *C to room temperature for 5 h. Upon completion of the reaction, the reaction mixture was poured into ice water and washed with CH 2 Cl 2 . The combined organic layers were washed with brine, dried over Na 2

SO

4 , filtered and concentrated in vacuo. The crude product was purified by silica gel column chromatography eluting with Hexanes:Ethyl acetate (9:1-1:1), and gave the product as an off 20 white solid (528 mg, 77%). HN N CI N CI 2,4-Dichloro-5H-pyrrolo[3,2-dpyrimidine To a suspension of 5-benzyl-2,4-dichloro-5H-pyrrolo[3,2-d]pyrimidine (177 mg, 0.64 25 mmol) in 1,2-dichlorobenzene (20 mL) was added AlC1 3 (852 mg, 6.4mmol). The reaction mixture was heated at 160 *C for 1.5 h, during which the reaction mixture became dark and homogeneous. Upon completion of the reaction, the reaction mixture was cooled, added

CHC

3 and washed with NH 4 Cl. The combined organic layers were washed with brine, dried over Na 2

SO

4 , filtered, and concentrated in vacuo. Added Hexanes and filtered off the WO 2006/122003 PCT/US2006/017677 44 product as purple solids (100 mg, 80%) and used for the next step without further purification. HN 0 N CI 5 2-Chloro-4-(4-cyclopropyl-2,6-dimethylphenoxy)-5H-pyrrolo[3,2-dpyrimidine To a stirred suspension of NaH (25 mg, 0.64 mmol) in dry NMP (1.5 mL) was added 4-cyclopropyl-2,6-dimethylphenol (103 mg, 0.64 mmol) and the resolution mixture was stirred at room temperature for 30 min under argon. The reaction mixture was added to a solution of 2,4-dichloro-5H-pyrrolo[3,2-dlpyrimidine (120 mg, 0.64 mmol) in dry NMP (1.7 10 mL) and heated at 90 *C for 16 h. After completion of the reaction, the resulting mixture was diluted with water and washed with EtOAc. The combined organic layers were washed with water, brine, dried over Na 2

SO

4 , filtered, and concentrated in vacuo. The crude product was purified by column chromatography, eluting with hexanes/ethyl acetate (4:1-2:1), to give the product as a light yellow solid (20.2 mg, 8%). 15 HN N CN 0 N N H 4-(4-(4-Cyclopropyl-2,6-dimethylphenoxy)-5H-pyrrolo[3,2-dlpyrimidin-2 ylamino)benzonitrile In a sealed tube was placed 2-chloro-4-(4-cyclopropyl-2,6-dimethylphenoxy)-5H 20 pyrrolo(3,2-d]pyrimidine (20 mg, 0.064 mmol), 4-aminobenzonitrile (31 mg, 0.26 mmol), TFE (0.21 mL) and TFA (0.04 mL, 0.51 mmol). The reaction mixture was stirred at 90 *C for 16 h. Upon completion of the reaction, the resulting mixture was diluted with water and washed with EtOAc. The combined organic layers were washed with NaHCO 3 , brine, dried WO 2006/122003 PCT/US2006/017677 45 over Na 2

SO

4 , filtered, and concentrated in vacuo. The crude product was purified by preparative TLC TLC, eluting with 5 % Acetone/CH 2

CI

2 to give the product as a light yellow solid (10.5 mg, 45%). 5 Example 12 -N N 0 N CI 2-Chloro-4-(mesityloxy)-5-methyl-5H-pyrrolo[3,2-dJpyrimidine To a stirred suspension of NaH (8.9 mg, 0.22 mmol) in dry NMP (1.0 mL) was added 10 2,4,6-trimethyl phenol (30.2 mg, 0.22 mmol) and stirred at room temperature for 30 min under argon. The reaction mixture was added to a solution of 2,4-dichloro-5-methyl-5H pyrrolo[3,2-d]pyrimidine (44.6 mg, 0.22 mmol) in dry NMP (1.0 mL) and heated at 90 *C for 16 h. After completion of the reaction, the resulting mixture was cooled, diluted with water and washed with EtOAc. The combined organic layers were washed with water, brine, dried 15 over Na 2

SO

4 , filtered, and concentrated in vacuo. The crude product was purified by column chromatography, eluting with hexanes/ethyl acetate (5:1-2:1), to give the product as a light yellow solid (52.7 mg, 80%). -N CN 0 N N H 20 4-(4-(Mesityloxy)-5-methyl-5H-pyrrolo[3,2-dlpyrimidin-2-ylamino)benzonitrile In a sealed tube was added 2-chloro-4-(mesityloxy)-5-methyl-5H-pyrrolo[3,2 d]pyrimidine (52.7 mg, 0.18 mmol), 4-aminobenzonitrile (83 mg, 0.70 mmol), TFE (1.0 rmL) and TFA (0.11 mL, 1.44 mmol). The reaction mixture was stirred at 90 0C for 48 h. Upon completion of the reaction, the resulting mixture was cooled, diluted with water and washed WO 2006/122003 PCTIUS2006/017677 46 with EtOAc. The combined organic layers were washed with NaHCO 3 , brine, dried over Na 2

SO

4 , filtered, and concentrated in vacuo. The crude product was purified by preparative TLC, eluting with hexanes:ethyl acetate (5:1-2:1), to give the product as a light yellow solid (65.7 mg, 95%). -N N 5 CN 4-(2-Chloro-5-methyl-5H-pyrrolo[3,2-d]pyrimidin-4-yloxy)-3,5-dimethylbenzonitrile To a stirred solution of NaH (42.1 mg, 1.05 mmol) in dry NMP (2.5 mL) was added 4-hydroxy-3,5-dimethylbenzonitrile (154.7 mg, 1.05 mmol) and stirred at room temperature 10 for 30 min under argon. The reaction mixture was added to a solution of 2,4-dichloro-5 methyl-5H-pyrrolo[3,2-d]pyrimidine (211.3 mg, 1.05 rmol) in dry NMP (2.7 mL) and heated at 160 *C for 16 h. After completion of the reaction, the resulting mixture was diluted with water and washed with EtOAc. The combined organic layers were washed with water, brine, dried over Na 2

SO

4 , filtered, and concentrated in vacuo. The crude product was 15 purified by column chromatography, eluting with hexanes/ethyl acetate (3:1-1:1), to give the product as a light yellow solid (294 mg, 85%). O N C N H CN 4-(2-(4-Cyanophenylamino)-5-methyl-5H-pyrrolo[3,2-d]pyrimidin-4-yloxy)-3,5 20 dimethylbenzonitrile In a sealed tube was added 4-(2-chloro-5-methyl-5H-pyrrolo[3,2-d]pyrimidin-4 yloxy)-3,5-dimethylbenzonitrile (294 mg, 0.94 mmol), 4-aminobenzonitrile (455 mg, 3.77 mmol), TFE (3.1 mL) and TFA (0.58 mL, 7.52 mmol). The reaction mixture was stirred at 90 *C for 48 h. Upon completion of the reaction, the resulting mixture was cooled, diluted WO 2006/122003 PCT/US2006/017677 47 with water and washed with EtOAc. The combined organic layers were washed with NaHCO 3 , brine, dried over Na 2

SO

4 , filtered, and concentrated in vacuo. The crude product was purified by preparative TLC, eluting with hexanes:ethyl acetate (4:1-1:2), to give the product as an off-white solid (133 mg, 40%). 5 Example 13 Bn-N N 0O CI 02 10 1-( 4 -(5-benzyl-2-chloro-5H-pyrrolo[3,2-d]pyrimidin-4-yloxy)-3,5 dimethylphenyl)ethanone To a stirred solution of NaH (31 mg, 0.78 mmol) in dry NMP (2 mL) was added 1-(4 hydroxy-3,5-dimethylphenyl)ethanone (127 mg, 0.78 mmol) and stirred at room temperature for 30 min under argon. The reaction mixture was added to a solution of 5-benzyl-2,4 15 dichloro-5H-pyrrolo[3,2-dlpyrimidine (216 mg, 0.78 mmol) in dry NMP (2.4 mL) and heated at 160 *C for 16 h. After completion of the reaction, the resulting mixture was diluted with water and washed with EtOAc. The combined organic layers were washed with water, 2% NaOH, brine, dried over Na 2

SO

4 , filtered, and concentrated in vacuo. The crude product was purified by column chromatography, eluting with hexanes/ethyl acetate (4:1-2:1), to give the 20 product as a light yellow solid (111 mg, 35%). Bn-N N CN ON N H 0 WO 2006/122003 PCT/US2006/017677 48 4-(4-(4-Acetyl-2,6-dimethylphenoxy)-5-benzyl-5H-pyrrolo[3,2-djpyrimidin-2 ylamino)benzonitrile In a sealed tube was added 1-(4-(5-benzy- 2 -chloro-5H-pyrrolo[3,2-d]pyrimidin-4 yloxy)-3,5-dimethylpheny1)ethanone (111 mg, 0.27 mmol), 4-aminobenzonitrile (129 mg, 1.1 5 mmol), TFE (1.7 mL) and TFA (0.2 mL, 2.16 mmol). The reaction mixture was stirred at 90 *C for 16 h. Upon completion of the reaction, the resulting mixture was cooled, diluted with water, and washed with EtOAc. The combined organic layers were washed with NaHCO 3 and brine; dried over Na 2 SO4; filtered; and concentrated in vacuo. The crude product was purified by silica gel column chromatography, eluting with hexanes:ethyl acetate (9:1-100 % 10 EtOAc), to give the product as an off-white solid (68 mg, 51%). HN N CN O N N H 0 4

-(

4

-(

4 -Acetyl-2,6-dimethylphenoxy)-5H-pyrrolo[3,2-djpyrimidin-2 ylamino)benzonitrile To a suspension of 4

-(

4

-(

4 -acetyl-2,6-dimethylphenoxy)-5-benzyl-5H-pyrrolo[3,2 15 d]pyrimidin-2-ylamino)benzonitrile (65 mg, 0.13 mmol) in 1,2-dichlorobenzene (5.3 mL) was added AIC1 3 (178 mg, 1.3 mmol). The reaction mixture was heated at 160 "C for 1.5 h, after which time the reaction mixture became dark and homogeneous. Upon completion of the reaction, the reaction mixture was cooled, CHC1 3 was added, and the mixture was washed with NH 4 Cl. The combined organic layers were washed with brine, dried over Na 2

SO

4 , 20 filtered, and concentrated in vacuo. The crude product was purified by silica gel column chromatography, eluting with hexanes:ethyl acetate (3:1), to give the product as a brown solid (41 mg, 77%). Example 14 25 WO 2006/122003 PCT/US2006/017677 49 Bn-N N 0 N C1 N 1-(4-(5-benzyl-2-5H-pyrrolo[3,2-d]pyrimidin-4-yloxy)-3,5-dimethylphenyl)-N,N dimethylmethanamine 5 To a stirred solution of NaH (80.4 mg, 1.0 mmol) in dry NMP (3 mL) was added 4 ((dimethylamino)methyl)-2,6-dimethylphenol (216.4 mg, 1.0 mmol) and the mixture was stirred at room temperature for 30 min under argon. The reaction mixture was added to a solution of 5-benzyl-2,4-dichloro-5H-pyrrolo[3,2-d]pyrimidine (216 mg, 0.78 mmol) in dry NMP (2.6 mL) and heated at 120 *C for 16 h. After completion of the reaction, the resulting 10 mixture was diluted with water and washed with EtOAc. The combined organic layers were washed twice with water, washed with, brine, dried over Na 2

SO

4 , filtered, and concentrated in vacuo. The crude product was purified by silica gel column chromatography, eluting with MeOH/CH 2 Cl 2 (10%-30%), to give the product as a tan solid (71 mg, 17%). Bn-N CN ON N H N 15 4-(5-benzyl-4-(4-((dimethylamino)methyl)-2,6-dimethylphenoxy)-5H-pyrrolo[3,2 dJpyrimidin-2-ylamino)benzonitrile In a sealed tube was added 1-(4-(5-benzyl-2-5H-pyrrolo[3,2-d]pyrimidin-4-yloxy) 3,5-dimethylphenyl)-N,N-dimethylmethanamine (70.7 mg, 0.17 mmol), 4-aminobenzonitrile 20 (78.9 mg, 0.67 mmol), TFE (1.1 mL) and TFA (0.1 mL, 1.3 mmol). The reaction mixture was stirred at 90 *C for 16 h. Upon completion of the reaction, the resulting mixture was cooled, diluted with water, and washed with EtOAc. The combined organic layers were washed with NaHCO 3 solution and with brine, dried over Na 2

SO

4 , filtered, and concentrated WO 2006/122003 PCT/US2006/017677 50 in vacuo. The crude product was purified by silica gel column chromatography, eluting with MeOH/CH2CI2 (20%-40%), to give the product as a tan solid (17 mg, 20%). HN N CN H N 5 4-(4-(4-((dimethylamino)methyl)-2,6-dimethylphenoxy)-5H-pyrrolo[3,2-djpyrimidin-2 ylamino)benzonitrile The benzyl group was removed according to the same procedure as described for example 13. 10 Example 15 Bn-N N 0 N CI

NO

2 5-benzyl-2-chloro4-(2,6-dimethyl-4-nitrophenoxy)-5H-pyrrolo[3,2-dipyrimidine 15 To a stirred solution of NaH (61.9 mg, 2.6 mmol) in dry NMP (4.7 mL) was added 2,6-dimethyl-4-nitrophenol (258.9 mg, 1.55 mmol) and stirred at room temperature for 30 min under argon. The reaction mixture was added to a solution of 5-benzyl-2,4-dichloro-5H pyrrolo[3,2-d]pyrimidine (431 mg, 1.55 mmol) in dry NMP (4 mL) and heated at 90 *C for 16 h. After completion of the reaction, the resulting mixture was diluted with water and 20 washed with EtOAc. The combined organic layers were washed twice with water, washed with brine, dried over Na 2

SO

4 , filtered, and concentrated in vacuo. The crude product was purified by silica gel column chromatography, eluting with hexanes:ethyl acetate (3:1-1:1), to give the product as a white solid (598 mg, 94%).

WO 2006/122003 PCT/US2006/017677 51 Bn-N N CN 0 N N H

NO

2 4-(5-benzyl-4-(2,6-dimethyl-4-nitrophenoxy)-5H-pyrrolo[3,2-djpyrimidin-2 ylamino)benzonitrile 5 In a sealed tube was added 5-benzyl-2-chloro-4-(2,6-dimethyl-4-nitrophenoxy)-5H pyrrolo[3,2-d]pyrimidine (598 mg, 1.46 mmol), 4-aminobenzonitrile (691 mg, 5.85 mnol), TFE (9.1 mL) and TFA (1.97 mL, 11.7 mmol). The reaction mixture was stirred at 90 'C for 16 h. Upon completion of the reaction, the resulting mixture was cooled, diluted with water and washed with EtOAc. The combined organic layers were washed with NaHCO 3 , brine, 10 dried over Na 2

SO

4 , filtered, and concentrated in vacuo. The crude product was purified by silica gel column chromatography, eluting with hexanes:ethyl acetate (3: 1-1:1), to give the product (442 mg, 60%). Example 16 15 CI HN N CN o NAN H 0 4-(4-(4-Acetyl-2,6-dimethylphenoxy)-7-chloro-5H-pyrrolo[3,2-d]pyrimidin-2 ylamino)benzonitrile To a solution of 4-(4-(4-acetyl-2,6-dimethylphenoxy)-5H-pyrrolo[3,2-d]pyrimidin-2 20 ylamino)benzonitrile (13 mg, 0.03 mmol) in CH 2

C

2 (1 mL) was added NCS (4.4 mg, 0.03 mmol) and the mixture refluxed for 16 h. After the completion of the reaction, the solvent was concentrated and purified by preparative TLC eluting with hexanes: ethyl acetate (2:1) to give the product (4.2 mg, 30%).

WO 2006/122003 PCT/US2006/017677 52 Example 17 CI HN N CN S N N' H 5 4-(7-Chloro-4-(mesitylthio)-5H-pyrrolo[ 3

,

2 -dlpyrimidin-2-ylamino)benzonitrile To a solution of 4 -(4-(mesitylthio)-5H-pyrrolo[3,2-d]pyrimidin-2 ylamino)benzonitrile (10 mg, 0.02 mmol) in CH 2

CI

2 (5 mL) was added NCS (2.8 mg, 0.02 mmol) and the resolution mixture refluxed for 16 h. After the completion of the reaction, the solvent was concentrated and purified by preparative TLC, eluting with hexanes:ethyl acetate 10 (3:1), to give the product (8.8 mg, 88%). Example 18 Br HN N CN S N Na H 15 4 -(7-bromo-4-(mesitylthio)-5H-pyrrolo[3,2-dpyrimidin-2-ylamino)benzonitrile To a solution of 4-(4-(mesitylthio)-5H-pyrrolo[3,2-d]pyrimidin-2 ylamino)benzonitrile (22.7 mg, 0.06 mmol) in CH 2 C1 2 (10 mL) was added NBS (10.5 mg, 0.06 mmol) and the resultant mixture was refluxed for 16 h. After completion of the reaction, 20 the solvent was concentrated and purified by reversed phase HPLC to give the product as a white solid (6.4 mg, 23%). Example 19 WO 2006/122003 PCT/US2006/017677 53 CI O N CN 0 N 'N'a H 4-(7-chloro-4-(mesityloxy)-5-methyl-5H-pyrrolo[3,2-d]pyrimidin-2-ylamino)benzonitrile To a solution of 4-(4-(mesityloxy)-5-methyl-5H-pyrrolo[3,2-d]pyrimidin-2 5 ylamino)benzonitrile (17.3 mg, 0.05 mmol) in CH 2 C1 2 (5 mL) was added NCS (6.03 mg, 0.05 mmol) and the resultant mixture was refluxed for 16 h. After completion of the reaction, the solvent was concentrated and purified by preparative TLC, eluting with hexanes:ethyl acetate (3:1), to give the product as an off-white solid (3.4 mg, 6%). 10 Example 20 CI -N N CN O N N H CN 4

-(

7 -Chloro-2-(4-cyanophenylamino)-5-methyl-5H-pyrrolo[3,2-d]pyrimidin-4-yloxy) 3,5-dimethylbenzonitrile 15 To a solution of 4

-(

2

-(

4 -cyanophenylamino)-5-methyl-5H-pyrrolo[3,2-d]pyrimidin-4 yloxy)-3,5-dimethylbenzonitrile (21.5 mg, 0.06 mmol) in CH 2 C1 2 (3 mL) was added NCS (7.3 mg, 0.06 mmol) and the resultant mixture was refluxed for 16 h. After completion of the reaction, the solvent was concentrated and purified by preparative TLC, eluting with Hexanes:Ethyl acetate (3:1), to give the product as a light yellow solid (13.2 mg, 56%). 20 Example 21 WO 2006/122003 PCT/US2006/017677 54 Br N CN O N N" H CN 4-(7-Bromo-2-(4-cyanophenylamino)-5-methyl-5H-pyrrolo[3,2-d]pyrimidin-4-yloxy) 3,5-dimethylbenzonitrile 5 To a solution of 4-(2-(4-cyanophenylamino)-5-methyl-5H-pyrrolo[3, 2 -d]pyrimidin- 4 yloxy)-3,5-dimethylbenzonitrile (58 mg, 0.15 mmol) in CH 2 Cl 2 (8 mL) was added NBS (29 mg, 0.16 mmol) and the resultant mixture was refluxed for 16 h. After completion of the reaction, the solvent was concentrated and purified by preparative TLC, eluting with hexanes:ethyl acetate (2:1), to give the product as a yellow solid (40 mg, 57%). 10 Example 22 CI HN N CN 0 N N H CN 4-(7-Chloro-2-(4-cyanophenylamino)-5H-pyrrolo[3,2-djpyrimidin-4-yIoxy)-3,5 15 dimethylbenzonitrile To a solution of 4-(2-(4-cyanophenylamino)-5H-pyrrolo[3,2-d]pyrimidin-4-yloxy) 3,5-dimethylbenzonitrile (28.1 mg, 0.07 mmol) in CH 2

C

2 (4 mL) was added NCS (9.9 mg, 0.07 mmol) and the resultant mixture was refluxed for 16 h. After completion of the reaction, the solvent was concentrated and purified by preparative TLC eluting with hexanes:ethyl 20 acetate (2:1), to give the product as a pink solid (20 mg, 65%).

WO 2006/122003 PCT/US2006/017677 55 Biological Activity Inhibition of HIV-1 Reverse Transcriptase 5 Numerous compounds were screened for inhibitory activity against human immunodeficiency virus type I (HIV-1) using a high throughput cell-based assay using HIV 1 expressing firefly luciferase as a reporter gene and pseudotyped with vesicular stomatitis virus envelope glycoprotein (VSV-G). Experimental procedures were essentially as described 10 by Connor et al. in Journal of Virology (1996), 70: 5306-5311 (Characterization of the functional properties of env genes from long-term survivors of human immunodeficiency virus type 1 infection), and Popik et al. in Journal of Virology (2002), 76: 4709-4722 (Human immunodeficiency virus type 1 uses lipid raft-co-localized CD4 and chemokine receptors for productive entry into CD4+ T cells). It should be particularly appreciated that the virus 15 contains two introduced mutations in the RT gene (KI03N and Y181C, created by PCR mutagenesis) that render the virus highly resistant to current non-nucleoside HIV-I drugs. Virus stocks were generated by cotransfection of plasmid DNA encoding VSV-G with vector pNL4-3Env(-)Luc(+) into 293T cells. Sixty-four hours after transfection, virus-containing medium was collected by centrifugation and stored frozen at -80* C. 20 HeLa cells were infected with the VSV-G pseudotyped virus in the presence of screening compounds in a 384-well microtiter plate format. Forty-eight hours after initial infection, lysis buffer and Luciferase Assay Reagent (Promega) was added to the cells and luciferase activity was determined by counting the resultant luminescence using a LJL 25 luminometer. Since the luciferase gene is carried in the virus genome, its expression level directly reflects the virus replication level in the presence of a compound. To evaluate the activity of the compounds against wild type HIV-1, the HeLa-JC53 cell line that expresses high levels of CD4 and CCR5 (see e.g., Platt et al. in Journal of 30 Virology (1998), 72: 2855-2864: Effect of CCR5 and CD4 cell surface concentrations on infection by macrophagetropic isolates of human immunodeficiency virus type 1) was modified by isolation of a stable cell line that expresses luciferase under the control of the HIV-1 promoter (long terminal repeat, i.e., LTR). HIV-1 infection of this cell line stimulates the transcription of luciferase from the HIV-1 promoter and the luciferase gene expression 35 level is proportional to the level of virus replication (Harrington et al. in Journal of Virology WO 2006/122003 PCT/US2006/017677 56 Methods (2000), 88: 111-115: Direct detection of infection of HIV-1 in blood using a centrifugation-indicator cell assay; and Roos et al. in Virology (2000), 273: 307-315: LuSIV cells: a reporter cell line for the detection and quantitation of a single cycle of HIV and SIV replication). Procedures for virus infection, compound testing and luciferase activity determination were the same as for the VSV-G pseudotyped HIV-1. Two approaches were used to evaluate the cytotoxicity of the positive compounds discovered in the HIV-1 virus assays. The first approach employed another modified HeLa JC53 cell line that constitutively expresses high level of luciferase without virus infection. The level of luciferase expression in these cells served as an indicator for cell replication in the presence of the compounds. Procedures for compound testing and luciferase activity determination were the same as for the virus infection tests. The other toxicity assay utilized HeLe-JC53 cells and a commercially available MTS assay kit (Promega) that measures the mitochondria function of the cells. Results The results are listed in Table A as EC50 (nM) and IC50 (nM). Table legend: A is < 10, B is between 10 and 100, C is > 100, ND is not determined. Note that many compounds of this invention exhibit activities on wild-type (WT) and resistant mutants below 10 nM. Table A EC6 0 ECro EC 6 o ECao Structure WT Y181C (nM) Y188L (nM) L1001. Cpd (nM) KIO3N (nM) OA B B B CLogP: 6.31119 NH 2 ap A B B C CLgP:7.1942 pr A A A A S I L9:5259___________________________________ WO 2006/122003 PCT/US2006IO 17677 57 ECs 0 ECs 0 ECs 0 ECSO Structure WTf YIBIC (rM) Y188L (nM) 11 001 Cpd (nM) KI 03N (nM) crcN HNA BBB N 05 'c A A A A CL~ogP: 5.71888 NC CrogP: 8.67519 NC CLogP: 5.8598M 8 J/po B C C C 8~gp .36008 9N CNA C C C NYcLogp-. s.a1219 10 'N JCN A BBB N 1 ~ N N CN A B A B 8~UP .5232 NHI 12 0Nk B C C C C,: ogP: 4.4398 WO 2006/122003 PCTIUS2006/01 7677 58

EC

5

'

0 Ecso EC 50 ECso Structure WT- YIBiC (nM) YI8BL (nM) 11001 Cpd(nM) KIO03N (nM) 13 §'rWZJ A A A A 1 CLooP:5 18 14 ~ J~~'o~e C C

N

Ci~gP. 6.24839 15 0-11 NH Bc C c ' cLogP: 4.67978 16 C CC CLooP: 8.01359 17 AFH B A B CL~gR 4.79382 18 BC C C C4.o9VP: 7.04473 19 AC A AB CLoaP: 6.16M8 20 1NN A B C C 88~g: .7838 21 A B BC l ?CLogP,. 6.1088 WO 2006/122003 PCT/US2006/O 17677 59 EC'so EC 80 ECSD EC 6 0 Structure WT Y181C (nM) Y188L (nM) LI 001 Cpd (nM) K103N (nM) a-NH 22_ A c c C 22 H~N N a N R.iI 7.1203 23 HN N , 0 A A A IB CLogP: 6.5"=3 24 B c c C HN N Y CogPA464848 /I-NH 25 NY,~(S A B 'IVCLQP 4.55288 26 N CN A B B C CLoqP: 5.71308 27 #-NH CNA B B B HN N' CLOgP: 7.17134 28 H8N N aC A A B B NH 29 1N CI C A C C ( j CLogP: 5.01638 30 HN N 'JOCN HN~C C C C CLogP: 5.42083 WO 2006/122003 PCT/US2006/01 7677 60 EC~o EC 5 0 EC.5o EC 5 0 Structure WT YI8IC (nM) VI 881 (nM) LIOOI-* Cpd (nM) KIO03N (nM) N crc 3-1 N C A B A -B N' C ; ngP: 6.34288 _________ 32 b.. ,i AAac B CC o NH 8LQP .87638 33 A B BH NN CLW: 0.75519 34fN Fc A A B B -N CLogP: 8.41174 35 pH A B C c CLogP: e.1 8285 d-NH 36 NA B C C 0 NN Ctog P: 5.71888 37 OrNA A A A 0N ClogP: 8.52119 38 N'kO~F B C C C CLMgP: 7.18147 /iNH 39AO.C C C C C CLIoCP: 7.1847 WO 2006/122003 PCT/US2006/017677 61

EC

6 o ECso ECSo ECso Structure WT Y181C (nM) Y188L (nM) L1001 Cpd (nM) KI 03N (nM) 40 B B C B N CLogP: 8.60982 41 N A A B B CLogP: 7.16208 42 HN CN A A A A 0 N CLegP: 8.4519 43 C B B C B 44 I B C C C I ClogP:.M9878 N 45 CN A A A B CLogP: 5.46143 46 C C C C Cl8gP: 8.2_ _7 47 CN B B C C N CtgP: 8857208 WO 2006/122003 PCT/US2006/0 17677 62 EC'so EC6 0 Ecso EC 50 Structure WTf YI8IC (nM) Y188L (nM) LI 001 Cpd .(nM) K103N (nM) 4 8 QN t c B B C C s aC -CCLOgP. 9.11123 CI 49 S, NCN A A A A 0N M CtogP: 8.18873 50 N -Ia NA A B C N' CtogP. 4.02888 51 K? CN A A A B. S N CLogP: 7.4042 52 1NA A A A CLogP: O.98519 CI 53 5 K~ CN A B BC N CLogP:&13777 A CI 54 CNA B B C N CtP: 9.83084 Br 55 ~ C A B B C S N4 CLogP: 8.28777 WO 2006/122003 63PCTJUS2006IO 17677 ECso ECrio ECS 50

EC

5 o CdStructure WT Y181C (nM) Y188L (nM) 11001 Cpd(nM) KIO03N (nM) 56 N CN~ B B B B CLogP-. 7.8818 O N C NCLogP: 6.46008 58 Q.NNJJ-NBB C c

N

CILoP. 8.59208 al 59 Ja "B B B B 0 N CL-ogP: 7.17908 60 Q- N ~CN A ABB N C~ucgP: 7.188 61 aNCN A A A A 0N N CtogP: 5.46119 62 -N~j jCN A A A A CLogP: 7.39368 63B B C C 8-IP .4"208 WO 2006/122003 PCT/US2006/01 7677 64 ECro ECso ECs 0

ECS

0 Structure WT YI8IC (nM) VI 881 (nM) LIOOI Cpd (nM) KIO03N (nM) A B C C 64 -:r CL~gp.8.&Uwe A A A C 65N 66 HN~ CN A A A A 0 1N CLogP: 6.73519 67 -NA A B A CLOOR. &19473 0 68 -2 o ~CN A A A A 69 ~ dN CN A A A A 4WP 6.111388 er 70 - ~~CN A A A A qCLagP: 6.26M8 71 ~ CN A A A A "~ICLOP: 8.86919 WO 2006/122003 PCT/US2006/O 17677 65 Contemplated Compounds and Prophetic Examples In addition to the examples listed above, this invention provides or contemplates many compounds, examples of which are shown in the tables that follow. 5 Table I Contemplated Compounds of Formula IA-I Ar N -N / N V 10 IA-i SAr V WZ 1. oo'-diCH 3 0-p-(GH=CHCN)phenyI CN H -CH 3 2. o'o'-diCH 3 0-p-(CH=CHCN)pheny1 CN benzyl GH 3 - 3. oo'-diCH 3 0-p-(CH=CHCN)phenyI CN benzyl H - 4. o,o'-diCH 3 0-p-(CH=CHCN)phenyI GN 3-Me-benzyl CH 3 5. oo'-diCH 3 O-p-(CH-CHCN)phenyl CN 4-Me-benzyl H 6. oo'-diCH 3 0-p-(CH=CHCN)phenyl CN 3-MeO-benzyl H 7. oo'-diCH 3 0-p-(CH--CHCN)phenyl CN 4-MeO-benzyl CH 8. o,o'-diCH 3 O-p-(CH=CHCN)phenyI CN H H 9. oo'-diCH 3 0-p-(CH=CHCN)phenyI CN H -Br 10. oo'-diCH 3 O-p-(CH=CHCN)phenyl CN cyclopropyl CH 2

CH

3 i i. oo'-diCH 3 0-P-(CH=CHCN)phenyI CN C1H 2

CF

3

CH

2

CH

3 12. o,o'-diCH 3 0-p-(CH=CHCN)phenyl CH=CHGN H CH 3 13. oo'-diCH 3 O-p-(CH=CHCN)phenyI GH=CHCN benzyl CH 3 14. o,o'.-diCH 3 O-p-(CH=CHCN)phenyI CH=CHCN benzy] H 15. 0,0 -diCH 3 0-p-(CH=CHCN)phenyl CH=CHCN 3-Me-benzyl cycl2Roroyl 16. 0,0 -diCH 3 0-p-(CH=CHCN)phenyl CHGCHCN 3-MeO-benzyl benzyl 17. o,o'-diCH 3 0-p-(CH=CHCN)phenyI CH=GHCN H H 18. oo'-diCH 3 O-p-(CH=CHCN)phenyl

C=-CCH

3

CH

2

CH

3

CH

3 19. 0,0 -diCH 3 O-p-(CH=CHCN)phenyl Cl CH 2 cH-CH2 H 20. oo'-diCH 3 O-P-(CH=CHCN)phenyl SO 2

CH

3

CH

2

CH=CH

2 H 2-1. oo'-diCH 3 O-p-(CH=CHCN)pbenyI C1 GH 2

CH

3

CH

2

CH

3 22. oo'diCH 3 0-p-(CH=CHCN)pheny1 Cl HH 23. 4-cyc opropylnaphth-I-yl CN H CH 3 24. 4-cyclopropylnaphth-l-yl CN benzyl CH 3 25. 4-cyclopropylnaphth-1-yl CN benzyl H 26. 4-cyclogropylnaphth-1-yl CN H H 27. 4-cyclopropylnaphth-1-yl CH=CHCN H CH 3 28. _4-cyclopropylnaphth-1-yl CH=CHCN benzyl CH 3 29. 4-ccLopropylnaphth-1-yl CH=CHCN benzyl H 30. 4-cyclopropylnaphth-l-yl CH=CHCN H H 31. 14-cyclopropylnaphth-1-yl I SO 2

NHCH

3 I CH 2 CN F WO 2006/122003 PCT/US2006/01 7677 66 SAr V W Z 32. 4-cyclopropylnaphth-1-yl SO 2

NHCH

3 cyclopropyl cl 33. oo'-di-CH 3 O-p-CN-phenyl SO 2

NH

2

CH

2 cH 2 CN Br 34. o,o'-di-CH 3 O-p-CN-phenyl SO 2

NH

2

CH

2 CN benzyl 35. o,o' -di-CH 3 0-p-CN-phenyl C=CCH 3 3-MeO-benzyl F 36. oo'-di-CH 3 O-p-CN-phenyl F 3-Me-benzyl Cl 37. oo'-di-CH 3 O-p-CN-phenyl CN H CH 3 38. oo'-di-CH 3 O-p-CN-phenyl CN benzyl CH 3 39. oo'-di-CH 3 O-p-CN-phenyl CN benzyl H 40. oo'-di-CH 3 O-p-CN-phenyl CN H H 41. o,o'-di-CH 3 O-p-CN-phenyl CH=CHCN H CH 3 - 42. oo'-di-CH 3 O-p-CN-phenyl CH=CHCN benzyl CH 3 43. o,o'-di-CH 3 O-p-CN-phenyl CH=CHCN benzyl H 44. oo'-di-CH 3 O-p-CN-phenyl CH=CHCN H H 45. 0,0 o -di-CH 3 -p-CN-phenyl CN H CH 3 - 46. oo'-di-CH 3 -p-CN-phenyl CN benzyl CH 3 3,5-di MeO S47. oo'-di-CH 3 -p-CN-phenyl CN benzyl CH 3 48. oo'-di-CH 3 -p-CN-phenyl CN benzyl H 49. o,o'-di-CH 3 -p-CN-_phenyl CN H H 50. 0,0 '-di-CH 3 -p-CN-phenyl CH=CHGN H CH 3 - 51. o,o'-di-CH 3 -p-CN-phenyl CH=CHCN benzyl CH 3 52. o,o'-di-CH 3 -p-GN-phenyl CH=CHCN benzyl H 53. o, o -di-CH 3 -p-CN-phenyl CH=CHCN H H 54. oo'-diCH 3 O-p-(CH=CHCN)phenyl CN H F 55. oo'-diCH 3 -p-(CH=CHCN)phenyl CN benzyl F 56. 0, o'-diCH 3 O-p-(CH=CHCN)phenyl CH=CHCN benzyl F 57. oo'-diCH 3 0-p-(CH=CHCN)phenyl CH=CHGN H F 58. 4-cyclopropylnaphth-1-yl CN H F 59. 4-cyclopropylnaphth-1-yl CN benzy F s0. 4-cyclopropylnaphth-1-yl CH=CHCN H F 61. 4-cyclopropylnaphth-1-yl CH=CHCN benzyl F 62. 0,0 o di-CH 3 O-p-CN-phenyl CN H F 63. oo'di-CH 3 O.-p-CN-phenyl CN benzyl F 64. oo'-di-CH 3 O-p-CN-phenyl CH=CHCN H F 65. o,o'-di-CH 3 07p-CN-phenyl CH=CHCN benzyl F 66. oo'.di-CH 3 -p-CN-phenyl CN H F 67. o,o'-di-CH-P-CN-phenyl CN benzyl F 68. 0,0 '-di-CH 3 -p-CN-phenyl CH=CHCN H F 69. oo'-di-CH 3 -p-CN-phenyl CH=CHCN benzyl F 70. o,o -diCH 3 0-p-(CHCHCN)phenyl SO 2

NH

2 H CH 3 71. 0,0 rdiCH 3 0-P-(CHCHCN)phenyl SO 2

NH

2 benzyl CH 3 72. oo'-diCH 3 -p-(CH=CHCN)phenyl SO 2

NH

2 benzyl H 73. oo'-diCH 3 0-p-(CH=CHCN)phenyl SO 2

NH

2 H H 74. oo'-diCH 3 O-p-(CH=CHCN)phenyl SO 2

NH

2 H CH 3 75. o,o'-diCH 3 0-p-(CH=CHCN)phenyl F benzyl CH 3 76. 1o,o'-diCH 3 O-P-(CH=CHCN)phenyl F benzyl H 77 ~'dC 3 -p-(CH'=CHCN)phenyl F I H H WO 2006/122003 PCT/US2006/017677 67 Ar V W z 78. 4-cyclopropylnaphth-1-yl SO 2

NH

2 H CH 3 79. 4-cyclopropylnaphth-1-yl SO 2

NH

2 benzyl CH3 80. 4-cyclopropyinaphth-1-yl SO 2

NH

2 benzyl H 81. 4-cyclopropylnaphth-1-yl SO 2 NH2 H H 82. 4-cyclopropylnaphth-1-yl F H CH 3 83. 4-cyclopropylnaphth-1-yl F benzyl CH 3 84. 4-cyclopropylnaphth-1-yl F benzyl H 85. 4-cyclopropylnaphth-1-yl F H H 86. o,o'-di-CH 3 0-p-CN-phenyl SO 2

NH

2 H CH3 87. o,o'-di-CH 3 0-p-CN-phenyl SO 2

NH

2 benzyl CH 3 88. o,o'-di-CH 3 0-p-CN-phenyl SO 2

NH

2 benzyl H 89. o,o'-di-CH 3 0-p-CN-phenyl SO 2

NH

2 H H 90. o,o'-di-CH 3 0-p-CN-phenyl F H CH3 91. o,o'-di-CH 3 0-p-CN-phenyl F benzyl CH3 92. o,o'-di-CH 3 0-p-CN-phenyl F benzyl H 93. o,o'-di-CH 3 0-p-CN-phenyl F H H 94. o,o'-di-CH 3 -p-CN-phenyl SO 2

NH

2 H CH 3 95. o,o'-di-CH 3 -p-CN-phenyl SO 2

NH

2 benzyl CH3 96. o,o'-di-CH 3 -p-CN-phenyl SO 2

NH

2 3-Me-benzyl CH3 97. o,o'-di-CH 3 -p-CN-phenyl SO 2

NHCH

3 benzyl H 98. o,o'-di-CH 3 -p-CN-phenyl S0 2

NH

2 benzyl H 99. o,o'-di-CH 3 -p-CN-phenyl SO 2

NH

2 H H 100. o,o'-di-CH 3 -p-CN-phenyl F H CH3 101. o,o'-di-CH 3 -p-CN-phenyl F benzyl CH3 102. o,o'-di-CH 3 -p-CN-phenyl F benzyl H 103. o,o'-di-CH 3 -p-CN-phenyl F H H 104. o,o'-diCH 3 0-p-(CH=CHCN)phenyl SO 2

NH

2 H F 105. o,o'-diCH 3 0-p-(CH=CHCN)phenyl SO 2

NH

2 benzyl F 106. o,o'-diCH 3 0-p-(CH=CHCN)phenyl F benzyl F 107. o,o'-diCH 3 0-p-(CH=CHCN)phenyl F H F 108. 4-cyclopropylnaphth-1-yl SO 2

NH

2 H F 109. 4-cyclopropylnaphth-1-yl SO 2

NH

2 benzyl F 110. 4-cyclopropylnaphth-1-yl F H F 111. 4-cyclopropyinaphth-1-yl F benzyl F 112. o,o'-di-CH 3 0-p-CN-phenyl SO 2

NH

2 H F .113. o,o'-di-CH 3 0-p-CN-phenyl SO 2

NH

2 benzyl F 114. o,o'-di-CH 3 0-p-CN-phenyl F H F 115. o,o'-di-CH 3 0-p-CN-phenyl F benzyl F 116. o,o'-di-CH 3 -p-CN-phenyl SO 2

NH

2 H F 117. o,o'-di-CH 3 -p-CN-phenyl' SO 2

NH

2 benzyl F 118. o,o'-di-CH 3 -p-CN-phenyl F H F 119. o,o'-di-CH 3 -p-CN-phenyl F benzyl F 120. 2,4,6-trimethyl phenyl CN H CH3 121. 2,4,6-trimethyl phenyl CN benzyl CH3 122. 2,4,6-trimethyl phenyl CN benzyl H 123. 2,4,6-trimethyl phenyl CN H -H 124. 2,4,6-trimethyl phenyl CH=CHCN H CH3 WO 2006/122003 PCT/US2006/0 17677 68 _ _Ar V W Z 125. 2,4,6-trimethyl phenyl CH=CHCN benzyl CH 3 126. 2,4,6-trimethyl phenyl CH=CHCN benzy H 127. 2,4,6-trimethyl phenyl CH=CHGN H H 128. 2,4,6-trimethyl phenyl CN H F 129. 2,4,6-trimethyl phenyl GN benzyl F 130. 2,4,6-trimethyl phenyl CH=CHCN H F 131. 2,4,6-trimethyl phenyl CH=CHCN bnzyl F 132. 2,4,6-trimethyl phenyl S0 2 N11 2 H CH 3 133. 2,4,6-trimethyl phenyl

SO

2

NH

2 benzyl CH 3 134. 2,4,6-trimethyl phenyl SO 2

NH

2 benzyl H 135. 2,4,6-trimethyl phenyl SO 2

NH

2 H H -136. 2,4,6-trimethyl phenyl F H CH 3 -137. 2,4,6-trimethyl phenyl F benzyl GH 3 138. 2,4,6-trimethyl phenyl F benzyl H -139. 4-cyclopropyl phenyl F H H -140. 4-cyclopropyl phenyl SO 2

NH

2 H F -141. 4-cyclopropyl phenyl SO 2

NH

2 benzyl F 142. _4-cyclopropyl phenyl F H F 143. 4-cyclopropyl phenyl F benzylF 144. o, o -dimethyl-p-cyclopropyl phenyl CN H CH 3 145. o, o -dimethyl-p-cyclopropyl phenyl CN benzyl Gil 3 146. oo'-dimethyl-p-cyclopropyl phenyl GN benzyl H 147. o, o -dimethyl-p-cyclopropyl phenyl CN H H 148. oo'-dimethyl-p-cyclopropyl phenyl CH=GHGN H Gil 3 149. o, o -dimethyl-p-cyclopropyl phenyl GH=CHGN benzyl Gil 3 150. oo'-dimethyl-p-cyclopropyl phenyl GH=GHGN benzyl H 151. o, o -dimethyl-p-cyclopropyl phenyl CH=CHCN H H 152. oo'-dimethyl-p-cyclopropyl phenyl CN HF 153. oo'-dimethyl-p-cyclopropyl phenyl GN benzyl F 154. o, o -dimethyl-p-cyclopropyl phenyl GH=CHGN H F 155. o,o'-dimethyl-p-cyclopropyl phenyl CH=GHGN benzyl F 156. 0,0 -dimethyl-p-cyclopropyl phenyl SO 2

NH

2 H CH 3 157. o, o '-dim ethyl-p-cyclopropyl phenyl S0 2

NH

2 benzyl Gil 3 158. o,o'-dimethyl-p-cyclopropyl phenyl SO 2

NH

2 benzyl H 159. o, o -dimethyl-p-cyclopropyl phenyl SO 2

NH

2 H H 160. o,o'-diniethyl-p-cyclopropyl phenyl F H Gil 3 161. o,o'-dimethyl-p-cyclopropyl phenyl F benzyl CH 3 162. o, o -dimethyl-p-cyclopropyl phenyl F benzy] H 163. o,o'-dimethyl-p-cyclopropyl phenyl F H H 164. o, o -dimethyl-p-cyclopropyl phenyl SO 2

NI{

2 H F 165. o~o'-dimethyl-p-cyclopropyl phenyl SO 2

NIH

2 benzyl F 166. o, o'-dimethyl-p-cyclopropyl phenyl F H F 167. oo'-dimethyl-p-cyclopropyl phenyl F benzyl F 168. o,o'-diCH 3 O-p-(CH=CHCN)phenyl CN CH 3

CH

3 169. 0,0 '-diCH3O-p-(GH=CHGN)phenyl CN cyclopropyl GH 3 170. o,o'-diCH 3 0-p-(CH=CHCN)phenyl GN cyclopropyl H 171. o,o'-diGH 3 O-p-(GW=GHGN~phenyl GN Gil 3

H

WO 2006/122003 PCT/US2006/017677 69 Ar V W Z 172. o,o'-diCH 3 0-p-(CH=CHCN)phenyl CN CH 3 CH3 173. o,o'-diCH 3 0-p-(CH=CHCN)phenyl CH=CHCN cyclopropyl CH3 174. o,o'-diCH 3 0-p-(CH=CHCN)phenyl CH=CHCN cyclopropyl H 175. o,o'-diCH 3 0-p-(CH=CHCN)phenyl CH=CHCN CH 3 H 176. 4-cyclopropylnaphth-1-yI CN CH 3

CH

3 177. 4-cyclopropy naphth-1-yl CN cyclopropyl CH 3 178. 4-cyclopropylnaphth-1-yl CN cyclopropyl H 179. 4-cyclopropyinaphth-1-yl CN CH 3 H 180. 4-cyclopropylnaphth-l-yl CH=CHCN CH 3

CH

3 181. 4-cyclopropylnaphth-1-yl CH=CHCN cyclopropyl CH3 182. 4-cyclopropylnaphth-1-yl CH=CHCN cyclopropyl H 183. 4-cyclopropylnaphth-1-yl CH=CHCN CH 3 H 184. o,o'-di-CH 3 0-p-CN-phenyl CN CH 3

CH

3 185. o,o'-di-CH 3 0-p-CN-phenyl CN cyclopropyl CH3 186. oo'-di-CH 3 0-p-CN-phenyl CN cyclopropyl H 187. o,o'-di-CH 3 0-p-CN-pheny1 CN CH 3 H 188. o,o'-di-CH 3 0-p-CN-phenyl CH=CHCN CH 3

CH

3 189. o,o'-di-CH 3 0-p-CN-phenyl CH=CHCN cyclopropyl CH3 190. o,o'-di-CH 3 0-p-CN-phenyl CH=CHCN cyclopropyl H 191. o,o'-di-CH 3 0-p-CN-phenyl CH=CHCN CH 3 H 192. o,o'-di-CH 3 -p-CN-phenyl CN CH 3 CH3 193. o,o'-di-CH 3 -p-CN-phenyl CN cyclopropyl CH 3 194. o,o'-di-CH-p-CN-phenyl CN cyclopropyl H 195. o,o'-di-CH 3 -p-CN-phenyl CN CH 3 H 196. oo'-di-CH 3 -p-CN-phenyl CH=CHCN CH 3

CH

3 197. o,o'-di-CH 3 -p-CN-phenyl CH=CHCN cyclopropyl CH 3 198. oo'-di-CHrp-CN-phnyl CH=CHCN cyclopropyl H 199. o,o'-di-CH 3 p-CN-phenyl CH=CHCN CH 3 H 200. o,o-diCH 3 0-p-(CH=CHCN)phenyl CN CH 3 F 201. o,o'-diCH30-p-(CH=CHCN)phenyl CN cyclopropyl F 202. o,o'-diCH 3 0-p-(CH=CHCN)phenyl CH=CHCN cyclopropy] F 203. o,o'-diCH 3 0-p-(CH=CHCN)phenyl CH=CHCN CH 3 F 204. 4-cyclopropylnaphth-1-yl CN CH 3 F 205. 4-cyclopropylnaphth-1-yl CN cyclopropyl F 206. 4-cyclopropylnaphth-1-yl CH=CHCN CH 3 F 207. 4-cyclopropylnaphth-1-yl CH=CHCN cyclopropyl F 208. o,o'-di-CH 3 0-p-CN-phenyl CN CH 3 F 209. o,o'-di-CH 3 0-p-CN-phenyl CN cyclopropyl F 210. o,o'-di-CH 3 0-p-CN-phenyl CH=CHCN CH 3 F 211. o,o'-di-CH 3 0-p-CN-phenyl CH=CHCN cyclopropyl F 212. o,o'-di-CH 3 -p-CN-phenyl CN CH 3 F 213. o,o'-di-CH 3 -p-CN-phenyl CN cyclopropyl F 214. o,o' -di-CHrp-CN-phenyl CH=CHCN CH 3 F 215. o,o'-di-CH 3 -p-CN-phenyl CH=CHCN cyclopropyl F 216. 0,0'-diCH 3 0-p-(CH-CHCN)phenyl SO2NH 2

CH

3

CH

3 217. o,o'-diCH 3 0-p-(CH=CHCN)phenyl SO 2

NH

2 cyclopropyl CH 3 218. o,o'-diCH 3 0-p-(CH=CHCN)phenyl SO 2

NH

2 cyclopropyl H WO 2006/122003 PCT[US2006/0 17677 70 ___Ar V W Z 219. o,o'-diCH 3 O-p-(CH=CHCN)phenyl SO 2 NHi 2

CH

3 H 220. oo'-diGH 3 O-P-(CHGCHGN)phenyl SO 2

NHCH

3 Gil 3

CH

3 221. o,o'-diCH 3 O-p-(CHGCHCN)phenyl F _ cyclopropyl -CH 3 222. o,o'-diCH 3 0-p-(CHGCHCN)phenyl F cyclopropyl H 223. oo'-diCH 3 O-p-(CH=CHCN~phenyl F GH 3 H 224. 4-cyclopropylnaphth-1-yI S0 2

NH

2

CH

3

CH

3 225. 4-cyclgpropynaphth-1-yl S0 2 N11 2 ycprylCH 3 226. 4-cyclopropylnaphth-1-yI S0 2 N11 2 cyclopropyl H 227. 4-cyclopropylnaphth-1-yi S0 2 N11 2

GH

3 H 228. 4- c dopropylaphth-I-yl FCH 3

CH

3 229. 4-cyclopropylnaphth-1-y F CYClOPTOpyl CH 3 230.__ _"c____________-1yl cyclopropyl H 231.___ ___________pht-1-l CH 3 H 23. o d-C30pCNphnCH 3

C

3 234. oo'-di-CH 3 0-p-CN-phenyl SO 2

NH

2 cyclopropyl Gil 3 235. 0,0 '-di-CH 3 0-p-CN-phenyl ___________ cyclopropyl H 236. 0,0 -di-CH 3 0-p-CN-phenyl __________ CH 3 H -237. 0,o'-di-CH 3 0-p-CN-henyl _________ Gi 3

-CH

3 238. 0,0 -di-CH 3 O-p-CN-phenyl F________ cyclopropyl Gil 3 239. 0,oo-di-CH3O-p-CN-phenjyl Fcyclopropyl H 240. 0,0 '-di-CH 3 0-p-CN-ghenyl FCH 3 H -241. o, a -di-C11 3 -p-GN-phenyl GilH C 3

CH

3 242. 0,0 -di-C11 3 -p-CN-phenyl ____________ cyclopropyl Gil 3 243. 0,0 -di-CH 3 -p-CN-phenyl S0N2cyclopropyl H 244. 0,0 -di-GH 3 -p-GN-phenyl ___________ Gi 3 H 245. 0,0 '-di-Cil 3 -p-GN-phenyl FCH 3

CH

3 246. 0,0 '-di-CH 3 -p-CN-phenyl Fcyclopropyl CH 3 247. 0,0 -di-CH 3 -p-CN-phenyl Fcyclopropyl H 248. oo'-di-CH 3 -p-CN-phenyl F Gil 3 H 249. o,o'-diCH 3 0-p-(CH=CHCN)phenyl SO 2

NH

2

CH

3 F 250. o,o'-diCH 3 0-p-(CH=CHCN)phenyl SO 2

NH

2 cyclopropyl F 251. o,o'-diCH 3 O-p-(GHGCHGN)phenyl F cyclopropyl F 252. oo'-diCH 3 0-p-(CH=CHCN)phenyj F CH 3 F 253. 4-cyclopropylnaphth-1-yl SO 2

NH

2 Gil F 264. 4-cyclopropylnaphth-1-yl SO 2

NH

2 cyclopropyl F 255. "ryclopropylnaphth-1-yl F Gil 3 F 256. 4-cyclopropylnaphth-1-yl F cyclopropyl F 257. oo'-di-GH 3 O-p-CN-phenyl SO 2

NH

2 Gil 3 F 258. 0,0 '-di-CH 3 0-p-CN-phenyl SO 2

NH

2 cyclopropyl F 259. o,o'-di-CH 3 O-p-CN-phenyl F Gil 3 F 260. oo'-di-G11 3 0-p-GN-phenyl F cyclopropyl- F 261. o,o'-di-GH 3 -p-CN-phenyl SO 2

NH

2 Gil 3 F 262. 0,0 '-di-GH 3 -p-GN-phenyl S0 2

NH

2 cyclopropyl F 263. o,o'-di-GH 3 -P-CN-phenyl F Gil 3 F 264. 0,0 -di-GH 3 -p-CN-phenyl F cyclopropyl F 26.4cclopropyl phenyl GN Gl H WO 2006/122003 71PCTJUS2006/0 17677 Ar V W Z 266. 2,4,6-trimethyl phenyl CN cyclopropyl CH 3 267. 2,4,6-trimetby phenyl CN cyclopropyl -H 268. 2,4,6-trimethyl phenyl CN CH 3 H 269. 2,4,6-trimethy p henyI CH=CHCN CH 3

CH

3 270. 2,4,6-trimethiyl phenyl CH=CHCN cyclopropyl CH 3 271. 2,4,6-trimethyl phenyl CH=CHCN cyclopropylH 272. 2,4,6-trimethyl phenyl CH=CHCN CH 3 H 273. 2,4,6-trimethyl phenyl CN CH 3 F 274. 2,4,6-trimethyl phenyl CN cyclopropyl F 275. 2,4,6-trimethyl phenyl CH=CHCN CH 3 F 276. 2,4,6-trimethyl phenyl CH=CHCN cyclopropyl F 277. 2,4,6-trimethy I henyI SO 2

NH

2

CH

3

CH

3 278. 2,4,6-timethyl phenyl SO 2

NH

2 _ cyclopropyl CH 3 279. 2,4,6-trimethyl phenyl S0 2 N11 2 cyclopropyl H 280. 2,4,6-trimethyl phenyl SO 2

NH

2

CH

3 H 281. 2,4,6-trimethyl phenyl F CH 3

CH

3 282. 2,4,6-trimethyl phenyl F cyclopropyl CH 3 283. 2,4,6-trirnethyl phenyl F cyclopropyl H 284. 4-cyclopropyl phenyl F CH 3 H 285. 4-cyclopropyl phenyl S0 2

NH

2

CH

3 F 286. 4-cyclogropy phenyl SO 2

NH

2 cyclopropyl F 287. 4-cyclopropyl phenyl F CH 3 F 288. 4-cyclopropyl phenyl F cyClopropy F -289. 2,4,6-trirnethyl phenyl CN CH 3 - -CH 3 290. oo'-dimethyl-p-cyclopropyl phenyl CN cyclopropyl C 3 291. o, o -dimethyl-p-cyclopropyl phenyl CN cyclopropyl H 292. o, o -dimethyl-p-cyclopropyl phenyl CN CH 3 H -293. o, o -dimethyl-p-cyclopropyl phenyl CH=CHCN c 3

CH

3 294. o, o -dimethyl-p-cyclopropyl phenyl CH=CHCN cyclopropyl CH 3 295. 0,0 o -dimethyl-p-cyclopropyl phenyl CH=CHCN cyclopropyl H -296. o, o -dimethyl-p-cyclopropyl phenyl CH=CHCN CH 3 H 297. o, o -dimethyl-p-cyclopropyl phenyl CN c 3 F 298. o, o -dimethyl-p-cyclopropyl phenyl CN _ cyclopropyl F 299. o, o -dimethyl-p-cyclopropyl phenyl CH=CHCN CH 3 F. 300. o, o -dimethyl-p-cyclopropyl phenyl CH=CHCN cyclopropyl F 301. o, o '-dimethyl-p-cyclopropyl phenyl SO 2

NH

2 c 3

CH

3 302. o, o 'dimethyl-p-cyclopropyl phenyl S0 2 N11 2 cyclopropyl CH 3 303. o, o '-dimethyl-p-cyclopropyl phenyl SO 2

NH

2 cyclopropyl -H 304. o,0 o-dimethyl-p-cyclopropyl phenyl SO 2

NH

2

CH

3 H 305. 0,0 o -dimethyl-p-cyclopropyl phenyl F CH 3 H 306. 0,0 '-dimethyl-p-cyclopropyl phenyl F cyclopropyl CH 3 307. 0,0 '-dimethyl-p-cyclopropyl phenyl F cyclopropyl H 308. 2,4,6-trimethyl phenyl F CH 3 H 309. 2,4,6-trimethyl phenyl SO 2

NH

2

CH

3 F 310. 2,4,6-trimethy p henyl S0 2

NH

2 cyclopropyl F 311. 2,4,6-trimethyl phenyl F CH 3 F 312. 2,4,6-triniethyl phenyl F cyclopropyl F WO 2006/122003 PCTJUS2006IO1 7677 72 ___r _ _ _ _ _ _V w z 313. o,o -di-CH 3 - -acetyl-phenyI CN CH 3 H 314. o,o'-di-CH 3 -p-acetyl-phenyl CN II H 315. o,o'-di-CH 3 -p-acetyl-phenyl CN CH 3 Cl 316.1 o,o'-i-CH 3 -p-acetl-phenyl CN H ci WO 2006/122003 PCT/US2006/O 17677 73 Table 2 Contemplated Compounds of Formula IA-2 Ar W N- N /N ~N'T V Ar V W z 1. oo'-diCH 3 O-p-(CH=CHCN)-phenyl CN F OH 3 2. o o-diCH- 3 0-p-(CH=CHCN)-phenyI CN berizyl CH 3 3. oo'--diCH 3 0-p-(CH=CHCN)-phenyI CN benzyl H 4. oo'--diCH 3 0-p-(CH=CHcN)-phenyI CN FH 5. o,o '-diCH 3 O-p-(CH=CHCN)-pheny1 CH=CHCN Cl CH 3 6. o,6'-diCH 3 0-p-(CH=CHCN)-phenyI CH=CHGN benzyl CH 3 7. o,o'-diCH 3 0-p-(CH=CHCN)-phenyI GH=CHCN benzyl H 8. 0,0 -diCH 3 O-p-(CH=CHCN)-phenyI CH-CHCN Cl H 9. 4-cyclopropylnaphth-1-yl O=-CCH 3 allyl ethyl 10. 4-cyclopropylnaphth-1-yl ON allyl ethyl 11. 4-cyclopropylnaphth-1-yl CN benzyl H 12. 4-cyclopropylnaphth-1-yl ON benzyl H 13. 4-cyclopropylnaphth-1-yl C=-OCH 3 allyl ethyl 14. 4-cyclopropylnaphth-1-yl CH=CHCN allyl ethyl 3-MeO 15. 4-cyclopropylnaphth-1-yl CH=CHCN benzyl H 16. 4-cyclopropylnaphth-1-yl CH=CHCN benzyl H 17. o, o -di-CH 3 0-p-CN-phenyl SO 2

NHCH

3 CH=CHCN CH 3 18. o,o'-di-CH 3 0-p-CN-phenyl ON CH=CHCN CH 3 19. oo -di-CH 3 0-p-CN-phenyl ON 3-Me-benzyl H 20. 1 o,o'-di-CH 3 0-p-CN-phenyl ON benzyl H 21. o,o'-di-CH 3 0-p-CN-phenyl OHOCHCN OHOCHON CH 3 22. oo'-di-CH 3 0-p-CN-phenyl OHOCHCN OH 2

OH

2 ON OH 3 23. oo'-di-CH 3 0-p-CN-phenyl CHOCHCN CH 2

CH

2 CN H 24. oo'di-CH 3 0-p-CN-henyl OH=OHON benzyl H 25. oo'-di-CH 3 0-P-(CH=CHCN)-phenyI ON OH 3 H 26. oo'-di-CH 3 0-.P-(CH=CHCN)-phenyI ON OH 3 benzyl 27. oo'-di-CH 3 0-p-(CH=CHCN)-phenyI ON H benzyI 28. oo'-di-CH 3 0-g-(CH=CHCN)-phenyI ON H H 29. oo 'di-CH 3 -p-(CH=CHCN)-phenyI CH=CHCN OH 3 H 30. oo 'di-CH 3 -p-(CH=CHCN)-phenyI CH=CHCN OH 3 benzyl 31. oo 'di-CH 3 Q-p-(CH-CHCN)-phenyI CH=CHCN H benzy] 32. oo'di-CH 3 0-p-(CH=CHCN)-phenyl CH=CHCN H H 33. 4-cyclopropylnaphth-1-yl ON OH 3 H 3.4-cyclopropylnaphth-1-yl ON OH 3 I benzy] 3.4-cyclopropylnaphith-I yl ON H benzyl 3.4-cyclopropylnaphth-1-yl ON H H WO 2006/122003 PCT/US2006/01 7677 74 Ar V Wz 37. 4-cyclopropyinaphth-1-yl CH=CHCN CH 3 H 38. 4-cyclopropylnaphth-1-yl CH=CHCN CH 3 benzyl 39. 4-cyclopropylnaphth-1-yl CH=CHCN H benzy] 40. 4-cyclopropylnaphth-1-yl CH=CHCN H H 41. oo'-di-CH 3 0-p-CN-phenyl CN CH 3 H 42. oo'-di-CH 3 0-p-CN-phenyl CN CH 3 benzyl 43. o, 0 -di-CH 3 O-p-CN-phenyl CN H benzy 44. o, o -di-CH 3 0-p-CN-phenyl CN H H 45. oo'.di-CH 3 O-p-CN-phenyl CH=CHCN CH 3 H 46. 6,o'-di-CH 3 0-p-CN-phenyl CH=CHCN CH 3 benzyl 47. oo'-di-CH 3 0-p-CN-phenyl CH=CHCN H benzyl 48. o,o'-di-C11 3 0-p-CN-phenyl CH=CHGN H H 49. o,o'-di-CH 3 -p-CN-phenyl GN CH 3 H 50. o,o'-di-CH 3 -p-CN-phenyl CN CH 3 benzyl 51. oo'-di-CH 3 -p-CN-phenyl CN H benzyl 52. oo .di-CH 3 -p-CN-phenyl CN H H 53. oo'-di-CH 3 -p-CN-phenyl CH=CHCN CH 3 H 54. 1 oo'-di-CH 3 -p-CN-phenyl CH=CHCN GH 3 be Iy 55. o,o'-di-CH 3 -P-CN-phenyl CH=CHCN H benzyl 56. oo'-di-CH 3 -p.-CN-phenyl CHGCHCN H H 57. oo'-di-CH 3 0-P-(CH=CHCN)-phenyl CN F H 58. oo'di-CH 3 0-p-(CH=CHCN)-phenyl CN F benzyl 59. oo'-di-CH 3 O-p-(CH=CHCN)-phenyl CH=CHCN F benzyl 60. 1 oo'-di-CH 3 O- p-(CH=CHCN)-phenyI GH=CHCN F H 61. 4-cyclopropylnaphth-1-yl CN F H 62. 4-cyclopropylnaphth-1-yl CN F benzyl 63. 4-cyclopropylnaphth-1-yl CHGCHGN F H 64. 4-cyclopropylnaphth-1-yl I CH=CHCN F benzyl 65. oo'-di-CH 3 O-p-CN-phenyl CN F H 66. oo'-di-C11 3 0-p-CN-phenyl CN F benzyl 67. o, o -di-CH 3 0-p-CN-phenyl CH=CHCN F H 68. oo'-di-C11 3 0-p-CN-phenyl CIH=CHCN F benzyl 69. oo'-di-CH 3 -p-CN-phenyl CN F H 70. 1 o,o'-di-CH 3 -p-CN-phenyl CN F benzyl 71. o,o'-di-CH 3 -p-CN-phenyl CH=CHGN F H 72. o, o -di-CH 3 -p-CN-phenyl CH=CHGN F benzyl 73. 0,0 '-diCH 3 0-p-(CH=CHCN)-phenyl S0 2 NHi 2

CH

3 H 74. o,o'-diCH 3 0-p-(CH=CHCN)-phenyl SO 2

NH

2

CH

3 benzI 75. 1 o,o'.-diCH 3 0-p-(CH=CHCN)-phenyl SO 2

NH

2 H benzy1 76. o,o'.diCH 3 0-p-(CH=CHCN)-phenyl S0 2 N11 2 H H 77. o,o'.diCH 3 0-p-(CH=CHCN)-phenyl SO 2

NH

2

CH

3 H 78. oo'-diCH 3 07-p-(CH=CHCN)-phenyl F CH 3 benzyl 79. oo'diCH 3 0-p-(CH=CHCN}.phenyl F H benzyl 80. o,o'-diCH 3 O-p-(CH=CHCN)-phenyl F H H 81. 4-cyclopropylnaphth-1-yl SO 2

NH

2

CH

3 H 82. 4-cyclopropylnaphth-1-yl S0 2 N11 2

CH

3 benzyl 83. 4-cyclopropylnaphth-1-yl SO 2

NH

2 H enzvl WO 2006/122003 PCT/US2006/O 17677 75 _ _Ar V W Z 84. 4-cyclopropylnaphth-1-yl

SO

2

NH

2 H' H 85. 4-cyclopropylnaphth-1-yl F CH 3 H 86. 4-cyclopropylnaphth-1-yl F CH 3 benzyl 87. 4-cyclopropylnaphth-1-yl F H benzyl 88. 4-cyclopropylnaphth-1-yl F H H 89. oo'-di-CH 3 0-p-CN-Phenyl

SO

2

NH

2

CH

3 H 90. o,o'-di-CH 3 O-p-CN-phenyl

SO

2

NH

2

CH

3 berig 91. oo'-di-CH 3 0-p-CN-phenyl

SO

2

NH

2 H - -benzy1 92. oo'-di-CH 3 0:p-CN-phenyl

SO

2

NH

2 H H 93. o,o'-di-CH 3 O-p-CN-phenyl F CH 3 H 94. oo'-di-CH 3 O-p-CN-phenyl F CH 3 benzyl 95. oo'-di-CH 3 O-p-CN-phenyl F H benzyl 96. oo'-di-CH 3 O-p-CN-phenyl F H H 97. oo'-di-CH 3 ]p-CN-phenyl S0 2 N11 2

CH

3 H 98. o,o'-di-CH 3 -p-CN-phenyl

SO

2

NI{

2

CH

3 be 99. oVo-di-CH 3 -P-CN-phenyl

SO

2

NH

2 H benzy 100. oo'-di-CH 3 -P-CN-phenyl

SO

2

NH

2 H H 101. 0,0 -di-CH 3 -p-CN-Phenyl F CH 3 H 102. oo'-di-CH 3 - -CN-phenyl F CH 3 benzy 103. o, o -di-CH 3 -p-CN-phenyl F .H be 1A 104. o,o'-di-CH3-p-CN-phenyl F H H 105. oo'.diCH30-p-(CH=CHCN)-phenyl

SO

2

NH

2 F H 106. oo -diCH 3 O-p-(CH--CHCN)-phenyl S0 2 N1 2 F be 1y 107. oo'.diCH 3 O-P-(CH=CHCN)-phenyl F F benzI 108. oo'.diCH3O-p-(CH=C C -phenyl F F H 109. 4-cyclopropylnaphth-1-yl

SO

2

NH

2 F H 110. 4-cyclopropylnaphth-1-yl

SO

2

NH

2 F benzyl i1l. 4-cyclopropylnaphth-1-yl F F H 112. 4-cyclopropylnaphth-17yI F F benzyl 113. oo'-di-GH 3 0-p-CN-phenyl

SO

2

NH

2 F H 114. o o'di-CH 3 0-p-MN-henyl

SO

2

NH

2 F benzy] 115. oo-i-CH 3 O-p-CN-phenyl F F H 116. oo-i-CH30-p-CN-phenyl F F benzyl 117. o,o'-i-CH 3 -p-CN-phenyl

SO

2

NH

2 F H 118. o, o -di-CH 3 -p-CN-phenyl

SO

2

NH

2 F benzyl 119. o,o'.di-CH 3 -p-CN-phenyl F F H 120. oo'-i-CH 3 -p-CN-phenyl F F benzyl 121. 4-cyclopropyl phenyl CN CHf 3 H 122. 4-cyclopropyl phenyl CN CH3 benzyl 123. 4-cyclopropyl phenyl CN H -benzyl 124. 4-cycdopropy phenyl CN H H 12. 2,4,6-trimethyl phenyl CH=CHCN CH 3 H 126. 2,4,6-trimethyl phenyl CH=CHCN CH 3 benzy] 127. 2,4,6-trimethiyl phenyl CH=CHCN H benzy] 1l28 2,4,6-trimethiyl phenyl CH=CHCN H H 1 29 2,4,6-trimethyl phenyl CNFH 130. 2,4,6-trimethy p henyl CN F benzI WO 2006/122003 PCTIUS2006IO1 7677 76 Ar V W Z 131. 2,4,6.-trimethyl phenyl CH=CHCN F H 132. 2,4,6-trimethyl phenyl CH=CHCN F benz1 133. 2,4,6-trimethyl phenyl SO 2

NH

2

CH

3 H 134.1 2,4,6-triinethyl phenyl SO 2

NH

2

CH

3 benzyl 135. 2,4,6-trimethyl phenyl SO 2

NH

2 H benzyl 136. 2,4,6-trimethyl phenyl SO 2

NH

2 H H 137. 2,4,6-trimethyl phenyl F CH 3 H 138. 2,4,6-trimethyl phenyl F CH 3 benzyl 139.1 2,4,6-trimethyl phenyl F H benzyl 140. 4-cyclopropyl phenyl F H H 141. 4-cyclopropyl phenyl SO 2

NH

2 F H 142. 4-cyclopropyl phenyl S0 2 N11 2 F benzyl 143. 4-cyclopropyl phenyl F F H 144. 4-cyclopropyl phenyl F F benzyl 145.1 o, o -diinethyl-p-cyclopropyl phenyl CN CH 3 H 146. oo'-dmethyl-p-cyclopropyl phenyl 'CN CU 3 benzyl 147. o, o'-imethyl-p-cyclopropyl phenyl CN H ben 1 148. oo'-dimethyl-p-cyclopropyl phenyl CN H H 149., o,o'-dimethyl-p-cyclopropyl phenyl CH=CHCN CH 3 H 150.1 o, o -dimethyl-p-cyclopropyl phenyl CH=CHCN CH 3 -benzyl 151.1 o,o'-diniethyl-p-cyclopropyl phenyl CH=CHCN H benzyl 152. oo'-dimethyl-p-cyclopropyl phenyl CH=CHCN H H 153. o, o -dimethyl-p-cyclopropyl phenyl CN F H 154. 0,0 '-diimethyl-p-cyclopropyl phenyl CN F benzyl 155. o, o -dimethyl-p-cyclopropyl phenyl CH=CHCN F H 156. oo'-dimethyl-p-cyclopropyl phenyl CH=CHCN F benzyl 157. o,o'-dimethyl-p-cyclopropyl phenyl SO 2

NH

2

CU

3 H 158. oo'-dimethyl-p-cyclopropyl phenyl SO 2

NH

2

CH

3 benzyl 159. o,o'-dimethyl-p-cyclopropyl phenyl SO 2

NH

2 H benzy] 160., oo'-dimethyl_-p-cyclopropyl phenyl SO 2

NH

2 H H 161. oo'-dimethyl-p-cyclopropyl phenyl' F CH 3 H 162. o,o'-dimethyl-p-cyclopropyl phenyl F CH 3 benzyl -1i63. o,0 o -dimethyl-p-cyclopropyl phenyl F H benzyl 164. o,o'-dimethyl-p-cyclopropyl phenyl F H H 1 65.1 oo'-dimethyl-p-cyclopropyl phenyl S0 2 N11 2 F H 166. o, o -dimethyl-p-cyclopropyl phenyl SO 2

NH

2 F benzy] 167. 2-methyl-4-cyclopropyl phenyl F FH 168. 2-methyl-4-cyclopropyl phenyl F F benzyl 169. oo'-diCH 3 0-p-(CH=CHCN)-phenyl CN CU 3

CU

3 170.1 o,o '-diCH 3 O-p-(CH=CHCN)-phenyl CN CH 3 -cyclopropyl 171.1 o,o -diCH 3 0-p-(CH=CHCN)-phenyl CN H cyclopropyl 172.1 o,oLdiCH 3 0-P-(CH=CHCN)-phenyl CN H CU 3 173.1 o,o LdiCH 3 O0p-(CH=CHCN)-phenyl CH=CHCN CH 3

CU

3 174.1 o,o '-diCH 3 O-p-(CH=CHCN)-plienyl CH=CHCN CU 3 cyclopropyl 175. o,o0 'diCH 3 O-p-(CH=CHCN)-phenyl CH=CHCN H cyclopropyl 176. o,o'-diCH 3 0-p-(CH=CHCN)-phenyl CH=CHCN H CU 3 177. 4-cyclopropylnaphth I-yl CN CH 3

CH

3 WO 2006/122003 PCTLJS2006IO 17677 77 __ _Ar V W Z 178. 4-cyclopropylnaphth-1-yl CN Gil 3 cyclopropyl 179. 4-cyclopropylnaphth-1-yl CN H _ cyclopropyl 180. 4-cyclopropylnaphth-1-yl CN H CH 3 181. 4-cyclopropylnaphth-1-yl GHGCHCN CH 3 Gil 3 182.1 4-cyclopropylnaphth-1-yl CH=CHCN CH 3 cyclopropyl 183.1 4-cyclopropylnapht-1-yl GH=GHGN Hcyopoy 184. 4-cyclopropylnaphth-1-yl GH=CHCN H CH 3 185. oo' di-GH 3 0-p-CN-phenyl GN GH 3

CH

3 186. oo'-di-GH 3 O:--N-phenyl GN GH 3 CYClopropyl 187. oo'-di-GH 3 O-p-CN-phenyl CN H cyoppy 188. o,o'-di-CH 3 0-p-CN-phenyl CN H Gil 3 189. o,o'-di-GH 3 0-p-GN-phenyl GH=CHCN GEL 3

CH

3 190. oo'.di-CH 3 O-p-CN-Phenyl GHGCHCN GH 3 c do ro I 191. oo'-di-GH 3 0-p-GN-phenyl GH=CHGN H c o ro 1 192.1 oo'-di-CH 3 0-p-CN-phenyl GH=CHGN H GEL 3 193.1 o,o'-di-CH 3 -P-CN-phenyl CN Gil 3

GEL

3 194. o,o'-&C-H 3 -p-GN-phenyl CN Gil 3 cyclopropyl 195. oo'-di-GH 3 -p-GN-phenyl CN H _ c__yclopropyj 196. oo'-di-GH 3 -p-CN-phenyl GN H GEL 3 197. o,o'-di-GH 3 -p-GN-phenyl CH=CHCN Gil 3

GH

3 198. oo'-di-GH 3 -p-GN-phenyl GH=CHCN Gil 3 cyclopropyl 199. 0,0 -di-GH 3 -p-GN-phenyl GH=CHGN H cyclopropyl 200. o,o' -di-CH 3 -p-GN-phenyl GH=CHCN H GEL 3 201. oo'diCH 3 0-p-(CH=CHGN)-phenyl GN F GEL 3 202. o,o'-diCH 3 0-p-(CH=GHCN)-phenyl GN F csyclo rop 1 203. oo '-diGH 3 O-p-(CH=GHCN)-phenyl GH-GHGN F cyclopropyl 204. oo'diGH 3 O-p-(GH=GHGN)-phenyl GH=GI-IN F Gil 3 205. 4-cyclopropylnaphth-1-yl GN F Gil 3 206. 4-cyclopropylnaphth-1-yl CN F ccoropyI 207. 4-cyclopropylnaphth-1-yl GHGCHGN F GH 3 208. 4-cyclopropylnaphth-1-yl CH-GHCN F cyc opropy1 209. oo'-di-GH 3 0-p-CN-phenyl GN F Gil 3 210. oo'-di-CH 3 0-p-GN-phenyl GN F cycloropyl 211. oo'-di-CH 3 O-p-CN-phenyl GH-GHGN F Gil 3 212. o,o'-di-GH 3 0-p-CN-phenyl GHGCHGN F cyclopropyl 213. o,o'-di-CEL 3 -p-GN-phenyl GN F Gil 3 214. o,o'..di-GH 3 -p-GN-phenyl GN F cyclopropyl 215. oo -di-GH 3 -p-GN-phenyl GEL=GHGN F Gil 3 216. oo'-di-GH 3 -p-GN-phenyl C~HGHGN F _ cyclopropyl 217. oo'-diCH30-p-(GH=GHCN)-phenyl

SO

2

NH

2 Gil 3 Gil 3 218. oo'-diGH30-p-(CH=GHCN)-phenyl S0 2

NH

2 Gil 3 cyclopropyl 219. oo'-diCil 3 O-p-(CH=GHGN)-phenyl S0 2

NH

2 H _ cyclopropyl 220. o,o '-diGH3O-p-(CH=GHCN)-phenyl

SO

2

NH

2 H Gil 3 221. o,o'-diCH30-p-(CHGCHCN)-phenyl S0 2

NH

2 Gil 3

GH

3 222. oo'-diGH30:p-(CHGELCN)-phenyl F Gil 3 cyclopropyI 223. o,o '-diGH3O-p-(CH=GHCN)-phenyl F H _ cyclopropyl 224. oo'-diGH 3 0-p-(CH=GHCN)-phenyl I F H GilH 3 WO 2006/122003 PCT[US2006/017677 78 Ar V W z 225. 4-cyclopropylnaphth-1-yl

SO

2

NH

2

CH

3

CH

3 226. 4-cyclopropylnaphth-1-yl

SO

2

NH

2

CH

3 cyclopropyl 227. 4-cyclopropylnaphth-1-yl

SO

2

NH

2 H cycopropyl 228. 4-cyclopropylnaphth-1-yl

SO

2

NH

2 H CH 3 229. 4-cyclopropylnaphth-1-yl F CH 3

CH

3 .230. 4-cyclopropylnaphth-1-yl F CH 3 cyclopropyl 231. 4-cyclopropylnaphth-1-yl F H cyclopropyl 232. 4-cyclopropylnaphth-1-yl F H CH3 233. o,o'-di-CH 3 0-p-CN-phenyl

SO

2

NH

2

CH

3

CH

3 234. o,o'-di-CH 3 0-p-CN-phenyl

SO

2

NH

2

CH

3 cyclopropyl 235. o,o'-di-CH 3 0-p-CN-phenyl

SO

2

NH

2 H cyclopropyl 236. o,o'-di-CH 3 0-p-CN-phenyl

SO

2

NH

2 H CH 3 237. o,o'-di-CH 3 0-p-CN-phenyl F CH 3

CH

3 238. o,o'di-CH 3 0-p-CN-phenyl F CH 3 cyclopropyl 239. o,o'-di-CH 3 0-p-CN-phenyl F H cyclopropyl 240. o,o'-di-CH 3 0-p-CN-phenyl F H CH3 241. o,o'-di-CH 3 -p-CN-phenyl

SO

2

NH

2

CH

3 CH3 242. o,o'-di-CH3-p-CN-phenyl

SO

2

NH

2

CH

3 cyclopropyl 243. o,o'-di-CH 3 -p-CN-phenyl

SO

2

NH

2 H cyclopropyl 244. o,o'-di-CH 3 -p-CN-phenyl

SO

2

NH

2 H CH3 245. o,o'-di-CH 3 -p-CN-phenyl F

CH

3 CH3 246. o,o'-di-CH 3 -p-CN-phenyl F CH 3 cyclopropyl 247. o,o'-di-CH 3 -p-CN-phenyl F H cyclopropyl 248. o,o'-di-CH 3 -p-CN-phenyl F H CH3 249. oo'-diCH30-p-(CH=CHCN)-phenyl

SO

2

NH

2 F CH3 250. o,o'-diCH30-p-(CH=CHCN)-phenyl

SO

2

NH

2 F cyclopropyl 251. oo'-diCH 3 0-p-(CH=CHCN)-phenyl F F cyclopropyl 252. o,o'-diCH30-p-(CH=CHCN)-phenyl F F CH3 253. 4-cyclopropylnaphth-1-yl

SO

2

NH

2 F CH3 254. 4-cyclopropylnaphth-l-yl

SO

2

NH

2 F cyclopropyl 255. 4-cyclopropylnaphth-1-yi F F CH3 256. 4-cyclopropylnaphth-1-yl F F cyclopropyl 257. o,o'-di-CH 3 0-p-CN-phenyl

SO

2

NH

2 F CH 3 258. o,o'-di-CH 3 0-p-CN-phenyl

SO

2

NH

2 F cyclopropyl 259. o,o'-di-CH 3 0-p-CN-phenyl F F CH3 260. o,o'-di-CH30-p-CN-phenyl F F cyclopropyl 261. o,o'-di-CH 3 -p-CN-phenyl

SO

2

NH

2 F CH 3 262. o,o'-di-CH 3 -p-CN-phenyl S0 2

NH

2 F cyclopropyl 263. o,o'-di-CH 3 -p-CN-phenyl F F CH3 264. o,o'-di-CH 3 -p-CN-phenyl F F cyclopropyl 265. 4-cyclopropyl phenyl CN CH 3 CH3 266. 2,4,6-trimethyl phenyl CN

CH

3 cyclopropyl 267. 2,4,6-trimethyl phenyl CN H cyclopropyl 268. 2,4,6-trimethyl phenyl CN H CH 3 269. 2,4,6-trimethyl phenyl CH=CHCN

CH

3 CH3 270. 2,4,6-trimethyl phenyl CH=CHCN CH 3 cyclopropyl 271. 2,4,6-trimethyl phenyl CH=CHCN H cyclopropyl WO 2006/122003 PCT/US2006/O 17677 79 Ar V Wz 272. 2,4,6-trimethyl phenyl CH=CHCN H CH 3 273. 2,4,6-trimethyl phenyl CN F CH 3 274. 2,4,6-trimethyl phenyl CN F cyclopropyl 275.1 2,4,6-trimethyl phenyl CH=CHCNFCH 276.1 2,4,6-trimethyl phenyl CH=CHCN F cyclopropyl 277.1 2,4,6-trimethyl phenyl

SO

2

NH

2

CH

3

CH

3 278.1 2,4,6-trimethyl phenyl

SO

2

NH

2

CH

3 cyclopropy1 279.1 2,4,6-trimethyl phenyl

SO

2

NH

2 H cycLoEropyl 280.1 2,4,6-trimethyl phenyl S0 2 N11 2 H CH 3 281. 2,4,6-trimethyl phenyl F CH 3

GH

3 282. 2,4,6-trimethyl phenyl F CH c cloroyl 283. 2,4,6-triniethyl phenyl F Hcyoppy 284. 2,4,6-trimethyl phenyl F H CH 3 285. 2,4,6-trimethyl phenyl

SO

2

NH

2 F CH 3 286. 4-cyclopropyl phenyl SO 2

NH

2 F C o ro y 287.~~~ ~~ 4-cclprpy phnyFF 288. 4-cyclopropyl phenyl F F cyco o 289.1 0, 4int--cyclopropyl phenyl FN FH CH 3 Y 29.1 o,o'-diniethyl-p-cyclopropyl phenyl CN CH 3 Ccoroy 291. 0,0 '-dimethyl-p-cyclopropyl phenyl CN CH cyclopropyl 292. oo'-dixnethyl-p-cyclopropyl phenyl CN H CH 3 o~ 293. oo'-dimethyl-p-cyclopropyl phenyl HCCN

CH

3

CH

3 294. oo-dimethyl-p-cyclopropyl phenyl CH=CHCN

CH

3 Cycoroy 295. oo'-dimethyl-p-cyclopropyl phenyl CH=CHCN CH cyclopropyl 296. oo-dimethyl-p-cyclopropyl phenyl CH=CHCN H cycoroy 297. o,o '-dimnethyl-p-cyclopropyl phenyl CHCCN F CH 3 298. o,o '-dimethiyl-p-cyclopropyl phenyl CN F Cycoroy 299. oo'-dimethyl-p-cyclopropyl phenyl CHCCN F CH 3 300. o, o -dimethyl-p-cyclopropyl phenyl CH=CHCN F CycHroy 301. oo'-dimethyl-p-cyclopropyl phenyl SO 2 CHNH FH cycoroy 302. o, o -dimethyl-p-cyclopropyl phenyl

SO

2

NH

2

CH

3 Cycoroy 303. oo'-diniethyl-p-cyclopropyl phenyl SO 2

NH

2 CH cyclopropyl 304. oo'-dimethylTp-cyclopropyl phenyl SO 2

NH

2 H cH 3 r 305. oo'-dimethyl-p-cyclopropyl phenyl F0NH CH CH 3 306. o, o '-dimethyl-p-cyclopropyl phenyl F CH 3 coroy 307. o, o '-dirnethyl-p-cyclopropyl phenyl F CH cycl~opropyl 308. oo'-dimethyl-p-cyclopropyl phenyl F H cH 3 oroy 309. o, o -dimethyl-p-cyclopropyl phenyl FONH F CH 3 309. oo -dimethyl-p-cyclopropyl phenyl SO 2

NH

2 F cyco3oy 311. o,o'-dimethyl-p-cyclopropyl phenyl F0NH F cycoroy 312. o,o'-dimethyl-p-cyclopropyl phenyl F F c H3oroy 313. Oo-diethy-p-cceyl phenyl FN H _ H= 314. oo'-di-CH3-p-acetyl-phenyl CN CH H 315. 0,0 -di-CH 3 -p-acetyl-phenyl CN CH Hl 315. oo-di-CH 3 -P-acetyl-phenyl CN H 3 ci WO 2006/122003 PCT/US2006/017677 80 Table 3 Contemplated Compounds of Formula IA-3 Ar w I N N N v\ z Ar V W Z 1. o,o'-diCH 3 0-p-(CH=CHCN)-pheny CN benzyl F 2. o,o'-diCH 3 0-p-(CH=CHCN)-phenyl CN benzyl C1 3. o,o'-diCH 3 0-p-(CH=CHCN)-phenyl CN allyl F 4. o,o'-diCH 3 0-p-(CH=CHCN)-phenyl CN allyl Cl 5. o,o'-diCH 3 0-p-(CH=CHCN)-phenyl CH=CHCN benzyl CH 3 3-MeO 6. o,o'-diCH 3 0-p-(CH=CHCN)-phenyl CH=CHCN benzyl CH3 3-Me 7. o,o'-diCH 3 0-p-(CH=CHCN)-phenyl CH=CHCN benzyl CH 3 8. o,o'-diCH 3 0-p-(CH=CHCN)-phenyl CH=CHCN allyl CH 3 9. 4-cyclopropylnaphth-1-yl CN CH 2

CH

3 H 10. 4-cyclopropylnaphth-1-yl CN isopropyl H 11. 4-cyclopropylnaphth-1-yl CN CH 2

CF

3 Br 12. 4-cyclopropylnaphth-1-yl CN CH 2

CF

3 Cl 13. 4-cyclopropylnaphth-1-yl CH=CHCN CH 2

CH

3 H 14. 4-cyclopropylnaphth-1-yl CH=CHCN CH 2

CH

3 Br 15. 4-cyclopropylnaphth-1-yl CH=CHCN CH 2

CF

3

CH

3 16. 4-cyclopropylnaphth-1-yl CH=CHCN CH 2

CF

3 H 17. o,o'-di-CH 3 0-p-CN-phenyl CN benzyl F 18. o,o'-di-CH 3 0-p-CN-phenyl CN benzyl Cl 19. o,o'-di-CH 3 0-p-CN-phenyl CN allyl F 20. o,o'-di-CH 3 0-p-CN-phenyl CN allyl Cl 21. 0,o'-di-CH 3 0-p-CN-phenyl CH=CHCN benzyl CH 3 22. o,o'-di-CH 3 0-p-CN-phenyl CH=CHCN benzyl Br 23. o,o'-di-CH 3 0-p-CN-phenyl CH=CHCN allyl CH 3 24. o,o'-di-CH 3 0-p-CN-phenyl CH=CHCN allyl H 25. o,o'-diCH 3 0-p-(CH=CHCN)-phenyl CN H F 26. o,o'-diCH 3 0-p-(CH=CHCN)-phenyl CN benzyl Cl 27. o,o'-diCH 3 0-p-(CH=CHCN)-phenyl CN benzyl H 28. o,o'-diCH 3 0-p-(CH=CHCN)-phenyl CN H H 29. o,o'-diCH 3 0-p-(CH=CHCN)-phenyl CN H CH3 30. o,o'-diCH 3 0-p-(CH=CHCN)-phenyI CH=CHCN benzyl CH3 31. oo'-diCH 3 0-p-(CH=CHCN)-phenyl CH=CHCN benzyl H 32. o,o'-diCH 3 0-p-(CH=CHCN)-phenyl CH=CHCN H H 33. 4-cyclopropylnaphth-l-yl CN H CH 3 34. 4-cyclopropylnaphth-1-yl CN benzyl CH 3 35. 4-cyclopropylnaphth-1-yl CN benzyl H WO 2006/122003 PCT/US2006/01 7677 81 Ar V W Z 36. 4-cyclopropyinaphth-1-yl CN H H 37. 4-cyclopropyinaphth-1-yl CH=CHCN H CH 3 38. 4-cyclopropylnaphth-1-yl GH=CHCN benzyl GB 3 39. 4-cyclopropylnaphth-1-yl CH=CHCN benzyl H 40. 4-cyclopropylnaphth-1-yl CH=CHCN H H 41. oo -di-CH 3 0-p-CN-phenyl CN H CH 3 42. 0,0 -di-CH 3 O-p-CN-phenyl GN benzyl CH 3 43. o,o'-di-CH 3 0-p-CN-phenyl GN benzyl H 44. oo'-di-CH 3 0-p-CN-phenyl CN H H 45. oo'-di-CH 3 O-p-CN-phenyl CH-CHGN H CH 3 46. oo'-di-CH 3 0-p-CN-Phenyl GH=CHCN benzyl CH 3 47. o,o'-di-CH 3 0-p-CN-phenyl CH=CHCN benzyl H 48. o,o'-di-CH 3 0-P-CN-Phenyl CH=CHCN H H 49. oo -di-CH 3 -p-CN-phenyl GN H CH 3 50. oo'-di-CH 3 -p-CN-phenyl CN benzyl CH 3 51. oo '-di-CH 3 -p-CN-phenyl CN benzyl H 52. o,o'-di-CH 3 -p-CN-phenyl CN H H 53. oo'-di-CH 3 -p-CN-phenyl CH=CHCN H CH 3 54. oo'-di-CH 3 -p-CN-phenyl GHGCHCN benzyl CH 3 55. oo'-di-CH 3 -p-CN-phenyl CH=CHGN benzyl .H 56. o, o -di-CH 3 -p-CN-phenyl CH=GHCN H H 57. oo'-diCH 3 0-p-(CH=CHCN)-phenyl CN H F 58. oo'diCH 3 0-P-(CH=CHCN)-phenyl CN benzyl F 59. oo'-diCH 3 O-p-(CH=CHCN)-phenyl CH=CHCN benzyl F 60. oo'-diCH 3 O-p-(CH=CHCN)-phenyl CH=CHCN H F 61. 4-cyclopropyinaphth-1-yl CN H F 62. 4-cyclopropylnaphth-1-yl CN benzyl F 63. 4-cyclopropylnaphth-1-yl CH=CHCN H F 64. 4-cyclopropylnaphth-1-yl CH=CHCN benzyl F 65. oo'-di-CH 3 0-p-CN-phenyl CN H F 66. oo'-di-CH 3 O-p-CN-phenyl CN benzyl F 67. oo'-di-CH 3 O-p-CN-phenyl CH=CHCN H F 68. o,o'-di-CH 3 O-p-CN-phenyl CH=CHCN benzyl F 69. oo'di-CH 3 -p-CN-phenyl CN H F 70. oo'-di-CH 3 -p-CN-phenyl CN benzyl F 71. oo'-di-CH 3 -p-CN-phenyl CH=CHCN H F 72.1 oo'-di-CH 3 -p-CN-phenyl CH=CHCN- benzyl F 73. oo'-diCH 3 O-p-(CH=CHCN)-phenyl

SO

2

NH

2 H CH 3 74. oo'-diCH 3 O-p-(CH=CHCN)-phenyl

SO

2

NH

2 benzyl CH 3 75. oo'-iCH 3 O-p-(CH=CHCN)-phenyl SO 2

NH

2 benzyl H 76. oo'-iCH 3 O-p-(CH=CHCN)-phenyl SO 2

NH

2 H H 77.1 o,o'-diCH 3 O-p-(CH=CHCN)-phenyl

SO

2

NH

2 H CH 3 78. oo'diCH 3 0-p-(CH=CHCN)-phenyl F benzyl CH 3 79. o,o'-diCH3O-p-(CH=CHCN)-phenyl F benzyl H 80. o,o'-diCH 3 0-p-(CH=CHCN)-phenyl F H H 81. 4-cyclopropylnaphth-1-yl

SO

2

NH

2 H CH 3 1 82. 1 4-cyclopropylnaphth-1-yl

SO

2

NI{

2 benzyl CH 3 WO 2006/122003 PCTIUS2006/O 17677 82 Ar V W z 83. 4-cyclopropylnaphth-I-yl

SO

2

NH

2 benzyl -H 84. 4-cyclopropyinaphth-1-yl

SO

2

NH

2 H H 85. 4-cyclopropylnaphth-1-yl F H CH 3 86. 4-cyclopropylnaphth-1-yl F benzyl

CH

3 87. 4-cyclopropylnaphth-1-yl F benzyl H 88._ 4-cyclopropylnaphth-1-yl F H H 89. oo-di-CH 3 0-p-CN-phenyl

SO

2

NH

2 H CH 3 90. Oo -di-CH 3 0-P-CN-phenyl

SO

2

N{

2 benzyl

CH

3 91. Oo -di-CH 3 O-p-CN-Phenyl

SO

2

NH

2 benzyl HI 92. o,o'-di-CH 3 0-p-CN-phenyl

SO

2

NH

2 H H 93. oo'-di-CH 3 O-p-CN-phenyl F H CH 3 94. 0,0 -di-CH 3 O-p-CN-phenyl F benzyl Gil 3 95. 0,0 -di-CH 3 0-p-CN-Phenyl F beazyl H 96. 0,0'-di-CH 3 0-p-CN-Phenyl F H H 97. 0,0'-di-CH 3 :p-CN-phenyl S0 2 N11 2 H Gil 3 98. 0,o'.di-CH 3 -p-CN-phenyl S0 2

NH

2 benzyl

CH

3 99. oo'-di-CH 3 -p-CN-Phenyl S0 2

NH

2 _ benzyl H 100, 0,0'-di-CH 3 -p-CN-phenyl

SO

2

NH

2 H H 101. 0,0'-di-CH 3 -p-CN-phenyl F H Gil 3 102. oo-di-GH 3 -p-CN-phenyl F benzyl

CH

3 103 o,o'-di-CH 3 7p-CN-phenyl F benzyl H 104. oo'-di-CH 3 -p-CN-phenyl F H H 105. oo'-diCH3O-p-(GH=CHCN)-phenyl

SO

2

NH

2 H F 106. oo'-diCH30-p-(CH-GHCN)-phenyl S0 2 N11 2 benzyl F 107, oo' diCH30-p-(CH-GHCn)-phenyl F benzyl F 108. oo-iH0p(HCC)pey F H F 109: 4-cyclopropylnaphth-1-yl

SO

2

NH

2 H F 110 4-cyclopropynaphth1-y

SO

2

NH

2 benzyl F I1I 4 -cyclopropynaphth-1Iy F H f 1124 4 -cyclopropylnaphth-1-yl F benzyl F 113. oo'-di-CH 3 0-p-CN-phenyl

SO

2

NH

2 H F 114. oo'-di-CH 3 0-p-CN-phenyl

SO

2

NH

2 benzyl F 115 oo'-di-CH 3 0-p-CN-phenyl F H F 116. oo'-di-CH3O-p-CN-phenyl F benzyl F 117. o,o'-di-CH 3 -p-CN-phenyl

SO

2

NH

2 H F 118. oo~di-CH 3 -p-CN-Phenyl

SO

2

NH

2 benzyl F 11i9 o, o -di-CH 3 -p-CN-phenyl F H F 120, o,o'-di-CH 3 -p-CN-phenyl F benzyl F 121. 2,4,6-triniethyl phenyl GN H GH 3 122._ 2,4,6-triniethyl phenyl GN benzyl

CH

3 123, 2,4,6-trimethyl phenyl GN benzyl H 1244 2,4,6-trimethyl phenyl GN H H 125 2,4,6-trimethyl phenyl CH=CHCN H GB 3 126. 2,4,6-trimethyl phenyl CHGCHGN benzyl

GH

3 174-cyclopropyl phenyl CH=CHCN benzyl H 128. 4-cyclopropyl phenyl GHGCHCN H H 129. 4-cyclopropy phenyl CN H F WO 2006/122003 PCT/US2006/01 7677 83 SAr V W Z 130. 4-cyclopropyl phenyl CN benzyl F 131. 4-cyclopropyl phenyl CH=CHCN H F 132. 2,4,6-trimethyl phenyl CH=-CHCN benzyl F 133 2,4,6-trimethyl phenyl SO 2

NH

2 H CH 3 134, 2,4,6-trimethyl phenyl SO 2

NH

2 benzyl CH 3 135, 2,4,6-trimethyl phenyl S0 2 N11 2 benzyl H 136. 2,4,6-trimethyl phenyl S0 2 N11 2 H H 137. 2,4,6-trimethyl phenyl F H CH 3 138 2,4,6-trimethyl phenyl F benzyl CH 3 139. 2,4,6-trimethyl phenyl F benzyl H 1 40. 2,4,6-trimethyl phenyl F H H -141. 2,4,6-trimethyl phenyl SO 2

NH

2 H F 142. 2,4,6-trimethyl phenyl S0 2 N11 2 benzyl F 143. 2,4,'6-trimethyl phenyl F H F 144, 2,4,6-trimethyl phenyl F benzyl F 145. 2,4,6-trimhethyl phenyl ON H CH 3 146. 2,4,6-trimethyl phenyl ON -benyl- CH 3 147, 2,4,6-trimethyl phenyl CN benzyl H 148, 2,4,6-trimethyl phenyl CN H H 149. 2,4,6-tiimethiyl phenyl CH=CHCN H CH 3 150, 2,4,6-trimethyl phenyl CH=CHON benzyl OH 3 151. 2,4,6-trimethyl phenyl CH=CHGN benzyl H 152. 2,4,6-trimethyl phenyl CH=CHCN H H 153. 2,4,6-triniethyl phenyl CN H F 154. 2,4,6-trimethyl phenyl ON benzyl F 155 2,4,6-trimethyl phenyl CH=CHCN H F 156. 2,4,6-trimethyl phenyl CH=CHON benzyl F 157. oo-dimethyl-p-cyclopropyl phenyl SO 2

NH

2 H OH 3 158. 0,0 o dimethyl-p-cyclopropyl phenyl SO 2

NH

2 benzyl OH 3 159, oo'-diniethyl-p-cyclopropyl phenyl SO 2

NH

2 benzyl H 160. oo'-dimethyl-p-cyclopropyl phenyl SO 2

NH

2 H H 161. o, o '-diniethyl-p-cyclopropyl phenyl F H CH 3 162. oo-dimethyl-p-cyclopropyl phenyl F benzyl CH 3 163, olo '-dimethyl-p-cyclopropyl phenyl F benzyl H 164. oo -dimethyl-p-cyclopropyl phenyl F H H 165. oo -dimethyl-p-cyclopropyl phenyl SO 2

NH

2 H F 166. oo -dimethyl-p-cyclopropyl phenyl SO 2

NH

2 benzyl F 167. o,o '-dimethyl-p-cyclopropyl phenyl F H F 168. oo -dimethyl-p-cyclopropyl phenyl F benzyl F 169. o,o'-diCH 3 0-p-(CH=CHCN)-phenyl CN CR 3

CH

3 170. o,o'-diCH 3 O-p-(CH=CHCN)-phenyl CN cyclopropyl OH 3 171, -oo-diCH 3 O-p-(CH=CHCN)-phenyl ON cyclopropyI H 172. oo -diCH 3 0-p-(CH=CHCN)-phenyI ON OH 3

H

173, oo'-diCH 3 O-P-(CH=CHCN)-phenyl CH=CHCN CR 3

CH

3 ~174. o,o '-diCH 3 O-p-(CH=CHCN)-phenyl CH=CHCN cyclopropyl- CH 3 1754 oo -diCH 3 O-p-(CH=CHCN)-phenyl ICH-CHCN cyclopropy H 1761 o,o'-diCH 3 O-p-(CH=CHCN)-phenyl I H=CHCN I R WO 2006/122003 PCT/US2006/0 17677 84 Ar V W z 177. 4-cyclopropylnapbth-1-yl GN Gil 3

CH

3 178. 4-cyclopropylnaphth-1-yi GN _cyclopropyl Ti 3 179. 4-cyclopropylnaphth-1-yl CN cyclopropyl H 1801 4-cyclopropylnaphth-l-yl GN __gH 3 H 181. 4-cyclopropylnapth-_-yl GH=CHGN Gil 3 Gl 3 182. 4-cyclopropylnaphth-1-yl GH=GHGN _cyclopropyl Gil 3 183. 4-cyclopropylnaphth-1-yi CH=CHCN cyclopropyl H 184. 4-cyclopropylnaphth-1-yl GHGCHGN

CH

3 H 185. oo'-di-CH 3 O-p-CN-phenyl GN

CH

3 Gil 3 186. 0,0'-di-CH 3 0-p-CN-phenyl GN cyclopropyl

CH

3 187. oo'-i-CH 3 0-p-CN-phenyl CN cyclopropyl H 188. o,0'-di-CH 3 0:p-CN-phenyl CN GH 3 H 189. o,o' -di-Gil 3 0-p-CN-phenyl GH=CHGN

CH

3

CH

3 190, Oo -di-CH 3 O-P-CN-henyl CH=CHCN cyclopropyl Gil 3 191. oo'-di-CH 3 0-p-CN-Phenyl CHGCHCN cyclopropyl H 192. Oo -di-CH 3 0-p-CN-Phenyl CH=CH-CN Gil 3 H 193. 0,0 -di-CH 3 -p-CN-phenyl GN

CH

3

GH

3 194. oo&-i-CH 3 -p-CN-phenyl GN cyclopropyl

GB

3 195. Oo -di-CH 3 -p-CN-phenyl CN cyclopropyl H 196 oo'-i-Gil 3 -p-CN-phenyl CN Gil 3 H 197, oo'-di-CH 3 -p-CN-phenyl GH=CHGN Gil 3

CH

3 198. oo'-di-CH 3 -p-CN-phenyl CH--GHCN cyclopropyl Gil 3 199. oo -di-CH 3 -p-CN-phenyl CHGCHCN cyclopropyl H 200 0,0'-di-CH 3 -p-CN-phenyl Gil=CHCN Gil 3 H 201, oo'diCH30-p-(CH=GHCN)-phenyl GN Gil 3 F 202. oo diCH 3 O-p-(GH=GFGN)-phenyl GN cyclopropyl F 203, o~o -diCH 3 0-p-(Gil=GHCN)phenyl GH=GHCN cyclopropyl F 204. oo'-diGH 3 -p-(CH=CHCN).phenyl CH=GHCN Gil 3 F 205.. 4-cyclopropylnaphtl-1-yl CN GH 3 F 206, 4-cyclopropylnaphth-1-yl GN cyclopropyl F 2071 4-cyclopropyinaphth-1-yl CH=CHGN Gil 3 F 208. 4 -cyclopropylnaphth-1-yi GH=GHGN cyclopropyl F 209. oo'-di-Cil 3 0-p-GN-Phenvl GN Gil 3 F 210. oo'di-CH 3 0-p-CN-p-henyl GN cyclopropyl F 211. ooL-iH 3 0:p-CN-phenyl CH=CHGN Gil 3 F 212. oo'-di-CH30-p-CN-phenyl CH=GHGN cyclopropyl- F 213. oo'di-CH3-p-CN-phenyl GN Gil 3 F 214 oo'di-CH 3 -p-CN-phenyl GN _.cyclopropyl F 215, o~o'-di-CH 3 -p-CN-phenyl CH=CHCN Gil 3 F 216. Oo di-GH 3 -p-GN-phenyl Cil=CHCN cyclopropyl F 217. oo'-iCH 3 O-p-(GJ3=GilNy-phenyl

SO

2

NI

2 Gil 3 Gil 3 218. 0,0 -diCil3O-p-(Gil=CHCN)-phenyl

SO

2

NH

2 -Yc do roP yI Gi 3 219 o, 0 ?diCi 3 -p-(Gil=ilGN)-phenyl

SO

2 Nil 2 -cyclopropyl H 220. oo'-diGH3O-p-(Gil=CHCN)-phenyl

SO

2

NH

2 Gil 3 il 221, o,o 'diGH3-p-(CH=CHGN)-phenyl

SO

2

NH

2 Gil 3 Gil 3 222. oo'diCil 3 0-p-(GH=CHCN).peny1 F -cc dopro I GH 223 oo0'diCil3O-p-(Gil=GilN-phenyl, F cyclo ro Iyl H WO 2006/122003 PCT/US2006/0 17677 85 SAr V W Z 224. o, o -diCH 3 0-p-(CH=CHCN)-phenyl F OH 3 H 225' 4-cyclopropylnaphth-1-yl

SO

2

NH

2 Gil 3

CH

3 226. 4-cyclopropylnaphth-1-yl

SO

2

NH

2 cyclopropyl CH 3 227. 4-cyclopropylnaphth-1-yl S0 2 N11 2 cyclopropyl H 228, 4-cyclopropylnaphth-1-yl

SO

2

NH

2

OH

3 H 229. 4-cyclopropylnaphth-1-yl F CH 3

CH

3 230. 4-cyclopropylnaphth-1-yl F cyclopropyl CH 3 231. 4-cyclopropylnaphth-1-yl F cyclopropyl H 232. 4-cyclopropylnaphth-1-yl F Gil 3

H

233. oo'-di-CH30-p-CN-phenyl S0 2 N11 2

OH

3 Gil 3 234. oo'-di-CH30-p-CN-phenyl

-SO

2

NH

2 cyclopropyl CH 3 235. o,o'-di-CH 3 0-p-CN-phenyl SO 2

NH

2 cyclopropyl H 236. oo'-di-CH30:p-CN-phenyl

SO

2

NH

2

OH

3 H1 237, oo'-di-CH 3 O-p-CN-phenyl F OH 3 0113 238, oo'-di-CH 3 0-P-CN-Phenyl F cyclopropyl 0113 239. oo'-di-CH30-p-CN-phenyl F cyclopropyl H 240. oo'-di-CH30-p-CN-Phenyl F 0113 H 241, O,o'-di-CH 3 -p-CN-phenyl

SO

2 Ni{ 2 Gl 3

OH

3 242. oo'-di-CH- 3 -p-CN-phenyl

SO

2

NH

2 cycIOPrOPYl Il 3 H 243, oo'-di-CH 3 -p-CN-phenyl

SO

2

NI-

2 cyclopropyl H 244. oo'-di-CH 3 -p-CN-phenyl

SO

2

NH

2

OH

3 H1 245, oo'-di-G11 3 -p-CN-phenyl F CH 3 0113 246. oo'-di-CH 3 -p-CN-phenyl F cyclopropyl H13 247. oo'-di-CH 3 -p-CN-phenyl F cyclopropyl H 248. oo'-di-CH 3 -p-CN-phenyl F Gil 3 H 249 oo'-diCH3O-p-(CH=CHCN)-phenyl

SO

2

NH

2 Gil 3 F 250, oo'-diCH 3 O-p-(Cil=CHCN)-phenyl

SO

2

NH

2 cyclopropyl F 251, oo-diCH30-p-(CH-CHCN)-phenyl F cyclopropyl F 252. oo'-diCH 3 0-p-(CH=CHCN)-phenyl F CH 3 F 253.__ 4-cyclopropylnaphth-1-yl

SO

2

NH

2 0113 F 254, 4-cyclopropylnaphth-1-yl

SO

2

NH

2 cyclopropyI F 255. 4-cyclopropylnaphth-1-yl F OH 3 F 256. 4-cyclopropylnaphth-l-yl F _cyclopropyl F 257. oo'-di-CH 3 0-p-CN-phenyl

SO

2

NH

2

OH

3 F 258. oo'-di-CH 3 0-p-CN-phenyl

SO

2

NH

2 cyclopropyl F 259. o,o -di-CH 3 0-p-CN-phenyl F Gil 3 F 260. o,o'-&iCH 3 O-p-CN-phenyl F cyclopropyl F 261. oo'-di-CH 3 -p-CN-phenyl

SO

2

NH

2

OH

3 F 262. oo'-di-011 3 7p-CN-phenyl

SO

2

NH

2 cyclopropyl F 263. o,o'-di-CH 3 -P-CN-phenyl F CH 3 F 264. oo'-di-CH 3 -p-CN-phenyl F cyclopropyl F 265. 4-cyclopropyl plienyl ON 0113 OH 3 266. 4-cyclopropyl phenyl ON cyclopropy CH 3 267. 2,4,6-trimethyl phenyl ON clpry H 268. 2,4,6-trimethyl phenyl ON O 3 H 269. 2,4,6-trirnethyl phenyl OH=OHON CH 3 I 0113 2701 2,4,6-trimethyl phenyl CH=CHC§N cy clopropyl OH 3 WO 20061122003 PCTJUS2006IO1 7677 86 ___Ar V W Z 271, 2,4,6-trimethyl phenyl GH=CHCN cyclopropyl 272, 2,4,6-trimethyl phenyl CHGCHCN Gil 3 273. 2,4,6-trimethyl phenyl CN GH 3 F 2741 2,4,6-trixnethyl phenyl CN cyclopropyl F 275. 2,4,6-trimethyl phenyl CHGCHGN Cil 3 F 276. 2,4,6-trimethyl phenyl CH=CHGN cyclopropyl F 277. 2,4,6-trimethiyl phenyl SO 2

NH

2 Gil 3

CH

3 278. 2,4,6-trimethyl phenyl SO 2

NH

2 cyclopropyl Gil 3 279, 2,4,6-trimethyl phenyl SO 2

NH

2 cyclopropyl H 280. 2,4,6-tiimethyl phenyl S0 2 N11 2 Gil 3 H 281, 2,4,6-trimethyl phenyl F Gil 3 Gil 3 282. 2,4,6-trimethyl phenyl F cyclopropyl Gil 3 283. 2,4,6-trimethyl phenyl F cyclopropyl H 284. 2,4,6-trimethyl phenyl F Gil 3 H 285, 4-cyclopropyl phenyl SO 2

NH

2 Gil 3 F 286. 4-cyclopropyl pheniyl SO 2

NH

2 cyclopropyl F 287. 4-cyclopropyl phenyl F GH 3 F 288. 4-cyclopropyl phenyl F _cyclopropyl F 289, 2,4,6-trimethyl phenyl GN Gl 3 Gil 3 290, 2,4,6-trimethyl phenyl GN cyclopropyl Gil 3 291. oo-diniethyl-p-cyclopropyl phenyl GN cycloproIy H 292. o, 0 '-dimethyl-p-cyclopropyl phenyl GN Gil 3 H 293, oo'-dimethyl-p-cyclopropyl phenyl CH=CHCN GH 3 Gil 2 294 0,0 -dinmethyl-p-cyclopropyl phenyl CH=GHGN cyclopropyl Gil 3 295, oo-dimethyl-p-cyclopropyl phenyl GH=CiGN_ cyclopropyl H 296. oo'-dimethyl-p-cyclopropyl phenyl CH=CHCN Gil 3 H 297. oo '-dimethyl-p-cyclopropyl phenyl GN CH 3 F 298 ,0 o-dimethyl-p-cyclopropyl phenyl GN cyclopropyl F 299, o, o'-imethyl-p-cyclopropyl phenyl GH=GHGN Gil 3 F 300, o, o -dixnethyl-p-cyclopropyl phenyl GH=CHGN cyclopropyl F 301. o,o'-iniethyl-p-cyclopropyl phenyl SO 2

NH

2 Gil 3 Gil 3 302. o, o '-dimethyl-p-cyclopropyl phenyl SO 2

NH

2 cyclopropyl Gil 3 303. oo'-diniethyl-p-cyclopropyl phenyl SO 2

NH

2 cyclopropyl H 304. oo -diniethyl-p-cyclopropyl phenyl SO 2

NH

2 Gil 3 H 305. o, o '-dimethyl-p-cyclopropyl phenyl F Gil 3 Gil 3 306. o, o '-imethy--cycloproy 1pheny1 F cyclopropyl Gil 3 307. o,o'-dimethyl-p-cyclopropyl phenyl F cyclopropyl H 308 o, o -dimethyl-p-cycloproy 1pheny1 F Gil 3 H 309. 2,4,6-trimethyl phenyl S0 2

NH

2 Gil 3 F 310, 2,4,6-trimethyl phenyl S0 2

NH

2 cyclopropyl F 311, 2,4,6-trimethyl phenyl F Gil 3 F 312. 2,4,6-trimethyl phenyl F cyclopropyl F 313. o,o'-di-Gil 3 -p-acetyl-phenyl GN H H 314. o, o -di-Gil 3 -p-acetyl-phenyl GN Gil 3 H 3154 o, o -di-Gil 3 -p-acetyl-phenyl CN H Cl 316 o, o '-di-CH 3 -p-acetyl-phenyl GN H 3 cl- WO 2006/122003 PCT/1JS2006/017677 87 Table 4 Contemplated Compounds of Formula IA-4 Ar W N N "N N>H /N V Ar V W Z * oo-iGH 3 O-p-(CH=CHCN)-phenyI CN H H * oo'-iCH 3 0-p-(CH=CHCN)-phenyI CN CH 3 H * oo'-iCH 3 0-p-(CH=CHCN)-phenyI GN F CH 3 * o,o'~diCH 3 0-p-(CH=rGHCN)-phenyI CN Cl Gil 3 * oo'-iCH 3 O-p-(CH=CHCN)-phenyI CN F H * o,o'-diCH 3 0-p-(CH--CHCN)-phenyI GH=CHGN cl H * oo'-iCH 3 0-p-(CH--CHCN)-phenyI CH=CHCN Br Gil 3 * oo'-diCH 3 0-p-(CH=CHCN)-phenyI GH=CHCN H GH 3 4-cyclopropylnaphth-1-yl CN H H 0. 4-cyclopropylnaphth-1-yl CN Gil 3 H 1. 4-cyclopropylnaphth-1-yl CN F CH 3 2. 4-cyclopropylnaphth-1-yl CN Cl GH 3 3. 4-cyclopropylnaphth-1-yl CH=CHCN Cl H 4. 4-cyclopropylnaphth-1-yi CH=CHGN Gil 3 H 5. 4-cyclopropylnaphth-1-yl CH=CHCN F - -CH 3 6. 4-cyclopropylnaphth-1-yl CH=CHCN Cl CH 3 7. oo-i-CH 3 0-p-CN-phenyl CN Br H S. oo'-di-CH 3 0:E-CN-Phenyl CN H -H __oo'.di-CH 3 O-p-CN-phenyl CN CH 3

CH

3 I_ oo'-di-CH 3 0-p-CN-phenyl CN F GH 3 1. oo '-di-CH 3 O-p-CN-phenyl CH=CHGN H H :2. oo -di-CH 3 O-p-CN-phenyl GH=CHGN GH 3 H 3. oo'di-CH 3 0-p-CN-phenyl CH=CHCN F CH 3 .4. o,o'-di-CH 3 O-p-CN-phenyl CH=CHCN Cl CH- 3 .5. o,o'-iCH 3 O-p-(CH=CHCN)-phenyI CN F CH 3 .6. oo'-diCH 3 O-p-(CH=GHCN)-phenyl CN Cl GH 3 7. oo'-diCH30-p-(CH=CHCN)-phenyI CN Cl H 8. o,o'-iCH 3 O-p-(CH=CHCN)-phenyI GN F H 9. o,o'-diCH 3 0-p-(CH--CHCN)-phenyI CN H GH 3 0. oo'-diCH 3 0-p-(CH=CHCN)-phenyI GH=CHCN CH 3

CH

3 1. oo'-diCH 3 0-p-(CH=CHCN)-phenyI GHGCHGN F H 2. 0,oo-diCH 3 O-p-(CH=CHCN)-phenyl GHGCHCN Gi H 3. 4-cyclopropylnaphth-1-yl GN H ethyl 4. 4-cyclopropylnaphth-1-yl GN Cl ethyl 5. 4-cyclopropylnaphth-1-yl GN F H 6. 4-cyclopropylnaphth-1-yl GN CI H WO 2006/122003 PCTIUS2006/017677 88 Ar V WZ 37. 4-cyclopropylnaphth-1-yl CHOCHON Br eth 1 38. 4-cyclopropylnaphth-1-yl OH=CHCN H 2 ethyl 39. 4-cyclopropylnaphth-1-yl CH=CHCN H H 40. 4-cyclopjopylnaphth-1-Yl OH=CHCN

OH

3 H 41. o, o -di-CH30-p-CN-phenyl CN F

OH

3 42. oo' di-CH 3 0-p-CN-phenyl ON Cl OH 3 43. oo'-di-CHQ-CN-phenyl ON Cl 7-H 44. oo&.di-CH30-p-CN-phenyl CN F H 45. 0,0'-di-CH30-p-CN-phenyl

OE-CCH

3 01 OH 3 46. oo'-di-CH 3 0-p-CN-phenyl OH=CHCN Br O_ H 3 47. oo'-di-CH30--CN-phenyl CH=CHCN Br H 48. oo'-di-CH30-p-CN-phenyl CH=CHCN H H 49. 0,0 'diCH3O-p-(CH=CHCN)-phenyl CN

OH

3 H 50. oo'-diCH30-P-(CH=CHCN)-phenyl ON

CH

3 benzy 51. oo'-diCH30-p-(CH=CHCN)-pheny ON H benzyl 52. 0,0'.diCH30-p-(CH=CHCN)-phenyl ON H H 53. oo'.diCH30-p-(CH=CHCN)-phenyl ON

OH

3 H 54. oo'-diCH30-p-(CH=CHCN)-phenyl OH=CHON

CH

3 benzyl 55. oo'-diCH3O-p-(C~HOHCN)-phenyl CH=CHCN H benzy 56. o,-o'-diCH30-p-(CHOCHCN)-phenyl CH=CHON H H 57. 4-cyclopropylnaphth-1-yl CN

CH

3 H 58. 4 -cyclopropylnaphth-1-yl ON

CH

3 benzyl 59. 4-cyclopropylnaphth-i-yi CN H benzyl 60. 4-cyclopropylnaphth-1iyl CN H H 61. 4-cyclopropylnaphth1-y~ OH=OHON

OH

3 H 62. - 4 -cyclogropylnaphth-1il CH=CHCN

OH

3 benzyl 63. 4-cyclopropylnaphth--vi OH=CHON H benzyl 64. 4-cyclopropylnaphth-1-yl CH=CHCN H H 65. oo 'di-CH 3 O-p-CN-phenyl CN OHf 3 H 66. olo'-di-CH30-P-CN-phenyl ON

OH

3 benzyl 67. O,o'-di-CH30-p-CN-Phenyl ON H benzy] 68. oo'.di-CH30-P-CN-phenyl ON H - H 69. oo'-di-CH30-P-CN-pheny CH=CHCN

OH

3 H 70. o,o'-di-CH30-p-CN-phenyl OHOCHON

CH

3 benzI 71. oo'-di-CH30-p-CN-phenyl OH=OHON H benz1 72. oo'di-CH30-p-CN-phenyl OH=OHON H - H 73. oo'di-CH3-p-CN-phenyl ON

OH

3 H 74. oo'-di-CH 3 -p-CN-phenyl CN

OH

3 benzyl 75. o, o -di-CH 3 -CN-phenyl ON H ben I 76.* olo~di-H 3 -P-CN-phenyl ON H H 77. olo'-di-CH3-P-CN-phenyl OH=OHON

OH

3 H 78. oo di-CH 3 -p-CN-pheny1 OH=OHON 0113 benzyl 79. oo'-di-CH 3 -p.-CN-phenyl OH=OHON H benzyl 80. oo'.i-CH 3 -p-CN-phenyl OH=OHON HH 81. o~o'.diCH30-p-(CH'OHON)-phenyl ON F H 82. oo' diCH30-p-(CH=CHCN)-pheny1 ON F benzyl 83. oo .diCH 3 0-p-(CH=CHCN)-pheny1 OHOCHON -F benzyI WO 2006/122003 PCTIUS2006O 17677 89 Ar V W Z 84. oo'-diCH 3 0-p-(CH=CHCN)-phenyl CHOCHCN F H 85. 4-cyclopropylnaphth-1-yl ON F H 86. 4-cyclopropylnaphth-1-yl CN F bny 87. 4-cyclopropylaphth-1-yl CH=CHCN F H 88. 4-cyclopropylnaphth-1-yl C~HOHCN 'F benzyI 89. oo'di-CH 3 0-p-CN-phenyl ON F H 90. o,o'-di-CH 3 0-p-CN-phenyl CN F benzyl 91. oo'-di-CH 3 07p-CN-phenyl CH=CHCN F H 92. oo'-di-CH 3 0-p-CN-phenyl CH=CHCN F benzyl 93. oo'-di-CH 3 -p-CN-phenyl ON F H 94. oo'-di-CH 3 -p-CN-Phenyl ON F benzyl 95. oo'-di-CH 3 -p-CN-phenyl -CH=CHCN F H 96. olo'-di-CH 3 -p-CN-phenyl CHOCHCN F benzyl 97. oo' diCH 3 0-p-(CH=CHCN)-phenyl SO 2

N[-

2

CH

3 H 98. oo'-diCH3O-p-(CH=CHCN)-phenyl

SO

2

NH

2

OH

3 benzyl 99. oo'-diCH 3 0-p-(CH=CHCN)-phenyl

SO

2

NH

2 H benzyl 100. oo'-diCH 3 0-p-(CH=CHCN)-phenyl

SO

2

NH

2 H H 101. oo-diCH 3 O-p-(CH=CHCN)-phepyl

SO

2

NH

2

CH

3 H 102. oo'-diCH 3 0-p-(OIF=CHCN)-phcnyl F OH 3 benzyl 103. o,o'-diCH 3 O-p-(CH=CHCN)-phenyl F H henzyl 104. o,o'-diCH 3 O-p-(CH=CHCN)-phenyl F H H 105. 4-cyclopropylnaphth-1-yl

SO

2

NH

2

OH

3 H 106. 4-cycopropynaphth--y~

SO

2

NH

2

CH

3 benzyl 107. 4-cycopropynaphth--y

SO

2

NH

2 H benzyl 108. .4-cyclopropylnaphth-1-yl

SO

2

NI{

2 H H 109. 4-cyclopropyinaphth-1-yl F OH 3 H 110. 4-cyclopropylnaphth-1-yl F OH 3 benzyl ill. 4-cyclopropylnaphth-1-yl F H benzyl 112. 4-cyclopropylnaphth-1-yl F H H 113. oo'-di-CH 3 O-p-CN-phenyl

SO

2

NH

2

OH

3 H 114. o,o'-di-CH 3 0-p-CN-phenyl

SO

2

NH

2

OH

3 benzyl 115. oo'.-H 3 0-p-CN-phenyl S0 2 N11 2 H benzyl 116. olo'-di-CH 3 0-p-CN-phenyl SO 2

NH

2 H H 117. oo'-di-CH 3 0-p-CN-phenyl F OH 3 H 118. oo'-di-CH30-p-CN-phenyl F CH 3 benzy] 119. o,o'-di-CH 3 0-p-CN-phenyl F H benzyl 120. oo'-di-CH 3 0-p-CN-phenyl F H H 121. o,o'-di-CH 3 7p-CN-phenyl S0 2 N11 2

OH

3 H 122. oo'di-CH 3 -p-CN-phenyl SO 2

NH

2

OH

3 benzy] 123. o,o'-di-CH 3 -p-CN-phenyl SO 2

NH

2 H benzyl 124. o,o'-di-CH 3 -p-CN-phenyl SO 2

NH

2 H H 125. oo'-di-CH 3 -p-CN-phenyl F OH 3 H 126. o~o'.di-CH 3 -p-CN-phenyl F OH 3 benzyl 127. oco'-di-CH 3 -p-CN-phenyl F H benzyl 128. o,o -di-CH 3 -p-CN-phenyl F H H 129. o,o'-diCH 3 O-p-(CH=CHCN)-phenyl S0 2 N11 2 F - H 130. o,o'-diCH 3 07p-(CH=CHCN)-plienyl I SO 2

NH

2 F benzyl WO 2006/122003 PCT/US2006/017677 90 Ar V W Z 131. o,o'-diCH 3 0-p-(CH=CHCN)-phenyl F F benzyl 132. o,o'-diCH 3 0-p-(CH=CHCN)-phenyl F F H 133. 4-cyclopropyinaphth-1-yl SO 2

NH

2 F H 134. 4-cyclopropylnaphth-1-yl S0 2

NH

2 F benzyl 135. 4-cyclopropylnaphth-1-yl F F H 136. 4-cyclopropylnaphth-1-yl F F benzyl 137. o,o'-di-CH 3 0-p-CN-phenyl SO 2

NH

2 F H 138. o,o'-di-CH 3 0-p-CN-phenyl SO 2

NH

2 F benzyl 139. o,o'-di-CH 3 0-p-CN-phenyl F F H 140. o,o'-di-CH 3 0-p-CN-phenyl F F benzyl 141. o,o'-di-CH 3 -p-CN-phenyl SO 2

NH

2 F H 142. o,o'-di-CH 3 -p-CN-phenyl SO 2 NH2 F benzyl 143. o,o'-di-CH 3 -p-CN-phenyl F F H 144. o,o'-di-CH 3 -p-CN-phenyl F F benzyl 145. 4-cyclopropyl phenyl CN CH 3 H 146. 4-cyclopropyl phenyl CN CH 3 benzyl 147. 4-cyclopropyl phenyl CN H benzyl 148. 2,4,6-trimethyl phenyl CN H H 149. 2,4,6-trimethyl phenyl CH=CHCN CH 3 H 150. 2,4,6-trimethyl phenyl CH=.CHCN CH 3 benzyl 151. 2,4,6-trimethyl phenyl CH=CHCN H benzyl 152. 2,4,6-trimethyl phenyl CH=CHCN H H 153. 2,4,6-trimethyl phenyl CN F H 154. 2,4,6-trimethyl phenyl CN F benzyl 155. 2,4,6-trimethyl phenyl CH=CHCN F H 156. 2,4,6-trimethyl phenyl CH=CHCN F benzyl 157. 2,4,6-trimethyl phenyl SO 2

NH

2

CH

3 H 158. 2,4,6-trimethyl phenyl SO 2

NH

2

CH

3 benzyl 159. 2,4,6-trimethyl phenyl SO 2

NH

2 H benzyl 160. 2,4,6-trimethyl phenyl SO 2

NH

2 H H 161. 2,4,6-trimethyl phenyl F CH 3 H 162. 2,4,6-trimethyl phenyl F CH 3 benzyl 163. 2,4,6-trimethyl phenyl F H benzyl 164. 2,4,6-trimethyl phenyl F H H 165. 2,4,6-trimethyl phenyl SO 2

NH

2 F H 166. 2,4,6-trimethyl phenyl SO 2

NH

2 F benzyl 167. 4-cyclopropyl phenyl F F H 168. 4-cyclopropyl phenyl F F benzyl 169. 2,4,6-trimethyl phenyl CN CH 3 H 170. 2,4,6-trimethyl phenyl CN CH 3 benzyl 171. 2,4,6-trimethyl phenyl CN H benzyl 172. o, o '-dimethyl-p-cyclopropyl phenyl CN H H 173. o, o '-dimethyl-p-cyclopropyl phenyl CH=CHCN CH 3 H 174. o,o'-dimethyl-p-cyclopropyl phenyl CH=CHCN CH 3 benzyl 175. o,o'-dimethyl-p-cyclopropyl phenyl CH=CHCN H benzyl 176. oo'-dimethyl-p-cyclopropyl phenyl CH=CHCN H H 177. o,o'-dimethyl-p-cyclopropyl phenyl CN F H WO 2006/122003 91PCT1US20061017677 Ar V W Z 178. 0,0 '-dimethyl-p-cyclopropyl penyl CN F benzyl 179. o,o'-dixnethyl-p-cyclopropyl phenyl CH=CHCN F H______ 180. o, o -dimethyl-p-eyclopropyl phenyl CH=CHCN F benzyl 181. o, o -dimethyl-p-cyclopropyl phenyl SO 2

NH

2

CH

3 H 182. o,o'-dimethyl-p-cyclopropyl phenyl SO 2

NI{

2

CH

3 benzyl 183. o,o'-dimnethyl-p-cyclopropyl phenyl S0 2 N11 2 H benzyl 184. oo'-dimethyl-p-cyclopropyl penyl SO 2

NH

2 H -H 185. oo'-dimethyl-p-cyclopropyl phenyl F CH 3 H 186. o, o '-dimethyl-p-cyclopropyl phenyl F CH 3 benzyl 187. o,0 o -dimethyl-p-cyclopropyl phenyl Fj H benzyl 188. o, o '-dimethyl-p-cyclopropyl phenyl F H H 189. oo -dinaethyl-p-cyclopropyl phenyl SO 2

NI{

2 F H 190. o, o -dimethyl-p-cyclopropyl phenyl SO 2

NH

2 F benzyl 191. 2,4,6-trimethyl phenyl F F H 192. 2,4,6-trimethyl phenyl F F benzyl 193. oo'-diCH 3 0-p-(CH=CHCN)-phen I CN CH 3 Gil 3 194. o,o '.diCH 3 0-p-(CH=CHCN)-phenyl GN CH 3 _ cyclO rOp I 195. oo'-diCil 3 0-p-(CH=CHCN)-phenyI CN H cycloropy1 196. oo'-diCil 3 O-p-(CH=CHCN -phenyl CN H Gil 3 197. oo'-diCH 3 0-p-(CH=CHCN)-phenyl CN Gil 3 CE 198. oo'-diCH 3 0-P-(CH=CHCN)-phenyl CH=CHCN Gil 3 cyclopropyl 199. oo'diCH 3 0-P-(CH=CHCN)-phenyl CH=CHCN H cyclopropyl 200. oo'-diCH 3 0-p-(CH=CilCN)-phenyl CH=CHCN H Gil 3 201. 4-cyclopropylnaphth-1-yl CN Gil 3 Gil 3 202. 4-cyclopropylnaphth-1-yl CN Gil 3 cyclopropyl 203. 4-cyclopropylnaphth-1-yl CN H cyclopropyl 204. 4-cyclopropylnaphtb-1-yl CN H CH 3 205. 4-cyclopropylnaphth-1-y IHCC H CH 3 206. 4-cyclopropylnaphth-1-yl CH=CHCN Gil 3 cyclopropyl 207. 4-cyclopropylnaphth-1-yl CHGCHCN H cyclopropyl 208. 4-cyclopropylnaphth-l-yI ________H____ 209. oo'-di-CH 3 O-p-CN-phenyl CN __________ 210. oo'-di-CH 3 0--p-CN-phenyl CN Gil 3 cyclopropyl 211. oo'-di-CH 3 0-p-CN-phenyl CN H cyclopropyl 212. o, o -di-CH 3 0-p-CN-phenyl CN H_______ 213. oo'-di-CH 3 O-p-CN-phenyl _____________ _________ 214. oo'di-.CH 3 0-p-CN-phenyl CH4CHCN Gil 3 cyclopropyl 215. oo'-di-CH 3 0-p-CN-phenyl CH=CHCN H _ _cyclopropyl 216. o, o'-di-Cil 3 0-p-CN-phenyl _____________ H_______ 217. oo'-di-CH 3 -p-CN-phenyl CN HC3 218. o,o'-di-Cil 3 -p-CN-phenyl CN Gil 3 cyclopropyl 219. oo'di-CH 3 -p-CN-phenyl CN H cyclopropyl 220. o,o'-di-CH 3 -p-CN-phenyl GN H Gil 3 221. o,o'-di-CH 3 -p-CN-phenyl CH=CHCN Gil 3 Gil 3 222. oo'-di-CH 3 -p-CN-phenyl CH=CHCN Gil 3 cyclopropyl 223. o, o -di-CH 3 -p-CN-phenyl CHGCHCN H _ cyclopropyl 224. o,o'-cli-CH 3 -p-CN-phenyl CHGCHCN H CH 3 WO 2006/122003 PCT/US2006/017677 92 Ar V w z 225. o,o'-diCH 3 0-p-(CH=CHCN)-phenyl CN F CH3 226. o,o'-diCH 3 0-p-(CH=CHCN)-phenyl CN F cyclopropyl 227. o,o'-dfCH 3 0-p-(CH=CHCN)-phenyl CH=CHCN F cyclopropyl 228. o,o'-diCH 3 0-p-(CH=CHCN)-phenyl CH=CHCN F CH3 229. 4-cyclopropylnaphth-1-yl CN F CH3 230. 4-cyclopropyInaphth-1-yl CN F cyclopropyl 231. 4-cyclopropyinaphth-1-yl CH=CHCN F CH3 232. 4-cyclopropylnaphth-1-yl CH=CHCN F cyclopropyl 233. o,o'-di-CH 3 0-p-CN-phenyl CN F CH3 234. o,o'-di-CH 3 0-p-CN-phenyl CN F cyclopropyl 235. o,o'-di-CH 3 0-p-CN-phenyl CH=CHCN F CH3 236. o,o'-di-CH 3 0-p-CN-phenyl CH=CHCN F cyclopropyl 237. o,o-di-CH 3 -p-CN-phenyl CN F CH3 238. o,o'-di-CH 3 -p-CN-phenyl CN F cyclopropyl 239. o,o'-di-CH 3 -p-CN-phenyl CH=CHCN F CH3 240. o,o'-di-CH 3 -p-CN-phenyl CH=CHCN F cyclopropyl 241. o,o'-diCH 3 0-p-(CH=CHCN)-phenyl SO 2

NH

2

CH

3 CH3 242. o,o'-diCH 3 0-p-(CH=CHCN)-phenyl SO 2

NH

2

CH

3 cyclopropyl 243. o,o'-diCH 3 0-p-(CH=CHCN)-phenyl SO 2

NH

2 H cyclopropyl 244. o,o'-diCH 3 0-p-(CH=CHCN)-phenyl SO 2

NH

2 H CH 3 245. o,o'-diCH 3 0-p-(CH=CHCN)-phenyl SO 2

NH

2

CH

3 CH3 246. o,o'-diCH 3 0-p-(CH=CHCN)-phenyl F CH 3 cyclopropyl 247. o,o'-diCH 3 0-p-(CH=CHCN)-phenyl F H cyclopropyl 248. o,o'-diCH 3 0-p-(CH=CHCN)-phenyl F H CH3 249. 4-cyclopropylnaphth-1-yl SO 2

NH

2

CH

3 CH3 250. 4-cyclopropylnaphth-1-yl SO 2

NH

2

CH

3 cyclopropyl 251. 4-cyclopropylnaphth-1-yl SO 2

NH

2 H cyclopropyl 252. 4-cyclopropylnaphth-1-yl SO 2

NH

2 H CH3 253. 4-cyclopropylnaphth-1-yl F CH 3 CH3 254. 4-cyclopropylnaphth-1-yl F CH 3 cyclopropyl 255. 4-cyclopropylnaphth-1-yl F H cyclopropyl 256. 4-cyclopropylnaphth-1-yl F H CH3 257. o,o'-di-CH 3 0-p-CN-phenyl SO 2

NH

2

CH

3 CH3 258. o,o'-di-CH 3 0-p-CN-phenyl SO 2

NH

2

CH

3 cyclopropyl 259. oo'-di-CH 3 0-p-CN-phenyl SO 2

NH

2 H cyclopropyl 260. o,o'-di-CH 3 0-p-CN-phenyl SO 2

NH

2 H CH3 261. o,o'-di-CH 3 0-p-CN-phenyl F CH 3 CH3 262. o,oLdi-CH 3 0-p-CN-pheny1 F CH 3 cyclopropyl 263. o,o'-di-CH 3 0-p-CN-phenyl F H cyclopropyl 264. o,o'-di-CH 3 0-p-CN-phenyl F H CH3 265. o,o'-di-CH 3 -p-CN-phenyl SO 2

NH

2

CH

3 CH3 266. o,o'-di-CH 3 -p-CN-phenyl S0 2

NH

2

CH

3 cyclopropyl 267. o,o'-di-CH 3 -p-CN-phenyl SO 2

NH

2 H cyclopropyl 268. o,o'-di-CH 3 -p-CN-phenyl SO 2

NH

2 H CH3 269. o,o'-di-CH 3 -p-CN-phenyl F CH 3

CH

3 270. o,o'-di-CH 3 -p-CN-phenyl F CH 3 cyclopropyl 271. o,o'-di-CH 3 p-CN-phenyl F H cyclopropyl WO 2006/122003 PCT/US2006/017677 93 Ar V W Z 272. o,o'-di-CH 3 -p-CN-phenyl F H CH3 273. o,o'-diCH 3 0-p-(CH=CHCN)-phenyl SO 2

NH

2 F CH3 274. o,o'-diCH 3 0-p-(CH=CHCN)-phenyl S0 2

NH

2 F cyclopropyl 275. o,o'-diCH 3 0-p-(CH=CHCN)-phenyl F F cyclopropyl 276. o,o'-diCH 3 0-p-(CH=CHCN)-phenyl F F CH 3 277. 4-cyclopropylnaphth-1-yl SO 2

NH

2 F CH 3 278. 4-cyclopropylnaphth-1-yl SO 2

NH

2 F cyclopropyl 279. 4-cyclopropylnaphth-1-yl F F CH 3 280. 4-cyclopropylnaphth-1-yl F F cyclopropyl 281. o,o'-di-CH 3 0-p-CN-phenyl SO 2

NH

2 F CH 3 282. o,o'di-CH 3 0-p-CN-phenyl SO 2

NH

2 F cyclopropyl 283. o,o'-di-CH 3 0-p-CN-phenyl F F CH 3 284. o,o'-di-CH 3 0-p-CN-phenyl F F cyclopropyl 285. o,o'-di-CH 3 -p-CN-phenyl SO 2

NH

2 F CH3 286. oo'-di-CH 3 -p-CN-phenyl SO 2

NH

2 F cyclopropyl 287. o,o'-di-CH 3 -p-CN-phenyl F F CH3 288. o,o'-di-CH 3 -p-CN-phenyl F F cyclopropyl 289. 2,4,6-trimethyl phenyl CN CH3 CH3 290. 2,4,6-trimethyl phenyl CN CH 3 cyclopropyl 291. 2,4,6-trimethyl phenyl CN H cyclopropyl 292. 2,4,6-trimethyl phenyl CN H CH3 293. 2,4,6-trimethyl phenyl CH=CHCN CH3 CH3 294. 2,4,6-trimethyl phenyl CH=CHCN CH3 cyclopropyl 295. 2,4,6-trimethyl phenyl CH=CHCN H cyclopropyl 296. 2,4,6-trimethyl phenyl CH=CHCN H CH 3 297. 2,4,6-trimethyl phenyl CN F CH 3 298. 2,4,6-trimethyl phenyl CN F cyclopropyl 299. 2,4,6-trimethyl phenyl CH=CHCN F CH 3 300. 2,4,6-trimethyl phenyl CH=CHCN F cyclopropyl 301. 2,4,6-trimethyl phenyl SO2NH2 CH3 CH3 302. 2,4,6-trimethyl phenyl SO2NH2 CH3 cyclopropyl 303. 2,4,6-trimethyl phenyl SO2NH2 H cyclopropyl 304. 2,4,6-trimethyl phenyl SO2NH2 H CH3 305. 2,4,6-trimethyl phenyl F CH3 CH3 306. 2,4,6-trimethyl phenyl F CH3 cyclopropyl 307. 2,4,6-trimethyl phenyl F H cyclopropyl 308. 2,4,6-trimethyl phenyl F H CH3 309. 4-cyclopropyl phenyl SO 2 NH2 F CH3 310. 4-cyclopropyl phenyl SO 2

NH

2 F cyclopropyl 311. 4-cyclopropyl phenyl F F CH3 312. 4-cyclopropyl phenyl F F cyclopropyl 313. o,o'-dimethyl-p-cyclopropyl phenyl CN CH3 CH 3 314. o,o'-dimethyl-p-cyclopropyl phenyl CN CH3 cyclopropyl 315. o,o'-dimethyl-p-cyclopropyl phenyl CN H cyclopropyl 316. o,o'-dimethyl-p-cyclopropyl phenyl CN H CH3 317. o,o'-dimethyl-p-cyclopropyl phenyl CH=CHCN CH3 CH 3 318. o,o'-dimethyl-p-cyclopropyl phenyl CH=CHCN CH3 cyclopropyl WO 2006/122003 PCTIUS2006/0 17677 94 ArV W Z 319. o, o -dimethyl-p-cycloptopyl phenyl. CHWCHCN H cyclopropyl 320. o, o Ldimethl-p-cyclopropyl phenyl CH=CHCN H CU 3 321. o, o -dimethyl-p-cyclopropyl phenyl CN F CU 3 322. 0,0 -dimethyl-p-cyclopropyl henyl CN F cyclopropyl 323. o, o -dixnethyl-p-cyclopropyl phenyl CH=CHCN F CU 3 324. o, o'-diniethyl-p-cyclopropyl phenyl CH=CHCN F cyclopropyl 325. o, o -dimethl-p-cyclopropyl phenyl SO 2

NH

2

CH

3

CU

3 326. o,0 o -dimethyl-p-cyclopropyl phenyl SO 2

NH

2

CH

3 cycdopropyI 327. oo'dimeth 1- -cyclopropl p henyl. SO 2

NH

2 H cyclopropyl 328. oo-dimethyl-p-cyclopropyl phenyl SO 2

NH

2 H CU 3 329. qo o-dimethyl-p-cyclopropyl phenyl F CU 3

CH

3 330. o, o -dimethyl-p-cyclopropyl phenyl F CH 3 -cyclopropyl 331. 0,0 -dimethyl-p-cyclopropyl phenyl F H Cyclopropyl 332. o, o -diniethyl-p-cyclopropyl phenyl F H CU 3 333. 2,4,6-trimethyl phenyl S0 2 N11 2 F CU 3 334. 2,4,6-trimethyl phenyl SO 2

NH

2 F cyclopropyl 335. 2,4,6-trimnethyl phenyl F F CH 3 336. 2,4,6-trimethyl phenyl F F cyclopropyl 337. o, o -di-CH 3 -p-acetyl-phenyl CN H H 338. o, o '-di-CH 3 -p-acetyl-phenyl CN. CH 3 H 339. oo'di-CH 3 :e-acetyl-phenyl CN H Cl 340. oo'-di-CH 3 -p-acetyl-phenyl CN CU 3 Cl Additional contemplated and prophetic examples, which are not exhaustive but merely representative of this invention, are shown below: 5 0 -C N 0 -l N .. C 0 N 0 N N \ /K) ON -N N N -- )-C~ \ N' H-& O > 0 N N\ 0/ Ci -N - C -N -00C N N HN I- N C -INa

N

WO 2006/122003 PCT/US2006/O1 7677 95 0 HN N N -N N CN N>Th Ki CN NN NN NH S c N s N

Claims (10)

1. A compound of formula /Ar NN N N H IA where the dashed line represents a double bond between either A and B or 13 and D: where T' is 0 or S; A is -N=, NZ or =CZ; 13 is =C-l or =N-; D is =CW or =N-. or NW. provided that two of A. B. and I) are -N= or N/. or NW: Z is -I. F, Cl. Br. Cl- 3 . CI-1 2 C1-1 3 , cyclopropyl. or hCnzyl. the phenyl moiety of' said henzyl optionally substituted with one or two groups sclectcd independently from methyl and methoxy, provided that when A is NZ, Z is neither F nor Cl; W is H, F, Cl. 3r, methyl, ethyl, cyclopropyl, allyl, C-12CF 3 , cyanomethyl. CI-I 2 CH 2 CN. CH=CH-ICN, or benzyl, the phenyl moiety of said benzyl optionally substituted with one or two groups selected independently from methyl and methoxy, provided that when ) is NW, W is neither F or Cl; V is F, Cl, CN, SO 2 CI-1 3 , SO 2 NHl12, SO 2 NI-ICI-3, CCC- 3 , or C-=CIICN; and Ar is one of (a), (b), (c), and (d) below (a) Rs R4 (b) . R5 R 5 RP RP R 4 (c) R - R 7 (d) R 6 - RI RP R' \ 'R" R9 R'O cWRPrMiWX'(.CWGAOI 7 WI) (-12U0212 -97 where the dashed lines in (a) represent optional double bonds; and where RP is Cl. Br, I, CN, methyl, ethyl, n-propyl, isopropyl, cyclopropylmethyl, C 3 .C6 cycloalkyl, CI-I=CIICN, acetyl, or NH-C 1 -C 6 alkyl, said alkyl and cycloalkyl groups optionally substituted with methyl, methoxy, halogen. or cyano; R 1 . R 5 . and R 6 are, independently, I-I, F. Cl. Br, Cl-I 3 , CH 2 F, C1F 2 . CF3. isopropyl. cyclopropyl. OC1 3 . OH, OCF 3 , NI- 2 and NICI-1 3 , or R6 and RP on adjacent ring atoms. together with the ring atoms to which they are attached, form an additional fuscd five-membercd ring: Q and Q' are, independently, N or CH; R7 is Cl, Br, . C-13. CF3, OC-13, isopropyl. cyclopropyl. /-butylI. or cyc lobuty 1: and R - I are. independently. -1 or Cl b with the proviso that when Ar is (c), and the AB.l) ring is imidazolo. R') and V are not both one of Cl-I 3 , CN, and CI-=C-ICN.

2. The compound of claim I, wherein Ar is (a) or (c).

3. The compound of claim 2, where R 6 either is I-I or is in the 2-position

4. The compound of claim 3. wherein Ar is selected from 4-cyclopropyl phenyl; 4 cyclopropylmethyl phenyl; 4-bromophenyl; 2-chloro-4-bromophenyl; 4-bromo-1-naphthyl: 4 cyclopropyl-l-naphthyl; 2,6-dimcthyl-4-cyanophenyl; 2.6-dimethoxy-4-cyanophenyl: 2.6 dimcthyl-4-(2-cyanocthenyl) phenyl; 2.6-dimcthoxy-4-(2-cyanoethenyl) phenyl: 2-methyl-4 cyclopropyl phenyl: 2,6-dimethyl-4-cyclopropyl phenyl; 2.6-di-tri lluoromCthyl-4-cyclopropyl phenyl; 2.4.6-trimethyl phenyl; and 2,6-dimethyl-4-acetyl phenyl.

5. The compound of claim 1. which is a compound of formula IA-3 Ar W I -N Nt N N N V N H IA-3 C NR~bf)CSCAIK67_ I lOC-2 11-f2112 - 98 6. The compound of claim 1. which is a compound of formula IA-4 Ar 0 W N N 1 N N V IA-4

7. The compound of claims 5 or 6, where Ar is 4-cyclopropyl-, 4-acetyl-, 4-methyl-. 4-bromo-. or 4-cyano-2,6-di-substituted phenyl.

8. The compound of claim 7, where V is CN, and where W and Z are, independently. H1. methyl, halo, or benzyl.

9. A compound of formula 113 HNAr D N N H I1B where the dashed line represents a double bond between either A and 13 or 13 and D: where A is -N=, NZ or CZ; 13 is CH or =N D is CW or =N-, or NW, provided that two of A. B. and D are -N= or NZ or NW; Z is -1, F, Cl, Br, ClH 3 , CI-1 2 C-1 3 , cyclopropyl, or benzyl. the phenyl moiety of said benzyl optionally substituted with methyl or methoxy, provided that when A is NZ, Z is neither F nor Cl; W is -1, F. Cl, 13r, methyl. ethyl, cyclopropyl, allyl, C-1 2 CF 3 . cyanomethyl. CHClH 2 CN. CI-=C-iCN. or benzyl. the phenyl moiety ofsaid benzyl optionally substituted with methyl or methoxy, provided that when ) is NW. W is neither F or C:L V is F. CL. CN. SO 2 C-1 3 , SO 2 N-k. SONIlCH-. C=CCH 3 . or CAl I=CIICN. and Ar is one of(a), (b). and (d) below: - 99 R4 R4 4 R -e R R6-- -- R5 R R R RP RP RR5R (a) (b) R 9 R 10 (d) where RP is Cl, Br, I, CN, methyl. ethyl, n-propyl, isopropyl, cyclopropylmethyl. C 3 .C cycloalkyl, CI-=CHCN, acetyl, or N-l-C 1 -C6 alkyl. said alkyl and cycloalkyl groups optionally substituted with methyl. methoxy. halogen, or cyano: RV RS, and R 6 are, independently. -1. F, CI. Br. CH 3 , CH 2 F, Cl-IL. C: isopropyl. cyclopropyl. OC-1 3 . OH. OCF 3 , NH 2 and NICI-1 3 ; Q and Q' are. independently. N or CH; 17 is Cl. Br. I CH 3 . CF1, OC1 3 , isopropyl. cyclopropyl. /-butyl. or cyclobutyl; and R8 - R" are, independently. -1 or Cl- 3 .

10. The compound of claim 9 which is a compound of formula 113-1 R P HN R 7 HN A N N H

113-1 where the dashed line represents a double bond between either A and 13 or 13 and D: A is -N=, NZ or CZ; 13 is CH or =N D is CW or =N-. or NW; provided that two of A. 13. and I) arc -N= or N/ or NW 7 is -1, F. Cl. Br. Cl-1. Cl C-11, cyclopropyl. or henzyl. the phenyl moiety of said henyl optionally substituted with methylv or methoxy. provided that when A is N%. / is neither 1 nor Cl; W is -1. F, Cl, Br, methyl, ethyl, cyclopropyl, allyl, C-1 1 Cl), C-I 2 CN. CI-HCN. CI-=CI-ICN, or benzyl, the phenyl moiety of said benzyl optionally substituted with methyl or methoxy, provided that when 1) is NW, W is neither F nor Cl; V is F, Cl, CN, SO 2 CH 3 , SO 2 NH 2 , SO 2 NI-ICH 3 , C=CC-1 3 , or C-=ClICN; provided that when both A and D are nitrogen, then V is other than CN or C-l=CCI-IN: t, k oR , , I) ('<-,C(;k1K 167 1 11-'>5? -100 RP is Cl. 13r, I, CN, CI-V=CH-CN, methyl. ethyl, n-propyl, isopropyl, cyclopropylmenthyl.C-C cycloalkyl, acetyl, and Nl-I-C 3 -C6, alkyl; R 6 isI, Cl, Br, C11 3 , CI-F Cl-I K CF 3 . iSOPr-opyl, cyclopr-opyl. 0Cl-1 3 - 01-!. Gel-:. Nl-l, and N 1-1 C 1-13; IZ 7 is Cl, 13r, I, Cl-I 3 . CF 3 . 0C0-1 3 , isopropy!, cyclopropyl, /--hutyl. or cyciobuityl. 11. The compound of'claim 10, where V is CN or CI-l=CI-lCN, R' is 2-micthyl. 2-methoxy. or 2-chloro and RZ7 is I-1, 6-methyl, or 6-menthioxy. I2. Thc compound of'claimn 11I where W)~ is CN. cyc lopropy I. mecthyl. Br. Cl Cl 141 I ICN. or ac etyli. 13. The comnpound of claims I, where onc of A and 1) is N- and the other is NZ or NW. 14. The compound of claims 5 which is a com1pound of formula IA-3 selected From com1pounds in Table 3: Ar 01 w - N NN NN N H IA-') A r V W Z o,o'-diCl-l 3 (0-p-(Clil=Cl ICN)-phcnyl CN henlzyl 1:____ 0,0 'dC 10(C1-l =C1-ICN)-ph eny I CN hcnzyl C _ o, o'-diC 1- 3 0:1-(C -=C - CN)-pheny C N _________ __ 0,0' -iC 1-1 3 0:1-(C 1-1=C 1-CN) -phylC allyll 0,0 o-diC 1-1 3 0-p-(CI-H=C 1-1CN)-phenyl I CI-V=CI-ICN benzyl -(.113 _ 0.0 -(1iCl-l 3 0-p)-(Cl-k=Cl-lCN)-phenyl C -l=CI-ICN 3-MeG- c I, 0,0 -diCI-1 3 0-P-(CI-V=CI-ICN)-phienyI (O-VI=ICN 3)-Me-bcinzyl c__ 11 o, o -ciCl1-1 3 0-1)-(C1-1 CI-I CN)-phcnyl CI-l=CI-ICN allvI __ (II. 4-cyclopropy n phth-l-yl CN cI-11-13l-. 11 4-cyclopropyltiaplith-1-yl CN isopropyl ____H 4-cyclopropylnaphth-l-yl _ CN CI1-1 'C 3 1-- 3 __ 4-cyclopropy naph-lyCN _ CH-lCF C (I __ 4 -cyc IoplopyLtapRhth- I CI-l=CI-ICN CI-1 2 10-1 3 11 C 3NRF'c,113C(3SCG\ 3 1,7_j W)C.2 2'.152~ Ar V W z 4-cyclop olp Impith-1-yI CI VCH-CN C -11CH- 3 131 4-cyclopropylnaplith-l-yl (CI-I=CHI-CN ('I bCF l (: 1 3 -] ______ 4-c 'clopro nap ith-l-yl CI-VCCN CHICF: 3 ___ 0.0 -di-CI-I 3 0-11-CN-phenyl ___CN henzyL F _____ 0 o-di- C1- 3 0-1p- CN -phenyl ____CN___ b z I7C oo'-di-CH- 3 O- -CN-phenylCd__ ally I- 0, O'-Ci-CH11 3 O-/)-C N -phey 'I CN. ___ ally! C I 0,0-di-CH- 3 0-j?-CN-phecnyL____ CI I=-Cl-ICN bcnz L _ _1r o,o'-di-CI-I 3 0-p-CN-phcnyl (ICl CCN ____ l bnC.IiI.; o, o'-di-C1-1 3 O-p-C N -phlicny I C'I-VCI-ICN all, -J- - u-II 0 ,0 '- iCI-1 3 - p- [=CN )-p yli iy C V l N lly II. .. 0,0 '-iC I-1 3 )-P-(C -1C HICN)-phcny I -- CN I-Izy C__ I o, o'-diC 1-1 3 ()-f-(C 1 C[1-1CN)-plhen yI C N - benz I I (11__ o,o'-.diCI-1 3 0-p)-(CI-I=CH-CN)-pheniyI CN bezy _1_ o,o'-diCI-1 3 0-P-(CI-I=CI-ICN)-phenyI CN 1-1 C__ I 13 o,o'-diCI-I 3 O-P-(CI-V=CI-lCN)-phcenyI Cl-l=CI1-ICN ___benzyl __ -13 0,0 '-diCH- 3 (O-p-(CH-=CH-CN)-phen ,,, CI-VCI-ICN bcnzyl ____._ I o,o'-diCI-1 3 0-p-(Ci-I=CI-ICN)-plicyI CI-VCI-ICN 1-1 _____ I 4-cyclop)ropyinaphih- I-YI C C C C - I-I -- CI I" 4-ecpjplph-I I__CN ___benlzyl ( 4-cyclop opvlnapjth-I-yl___ CN Iezy I 4-ceyelopr-olyliiaphil-yl), ___- ___I-(' I~ I ci 1 _: 4-eyelopropylInaphith-I-yl CI (:1 CIC N bclv I I; :1 4-cyclopropyinaplith-l-yi (1ICC benzyl I CII; 4-cyclo ropylnaphth-l-yl C ,I-I=CI-ICN 1enzy 1 4~o-yeioC-1proyNph-I-I C= IN 1__ -I C____13 0,0 '-(h-C1H 3 O-p-CN-phcny1 CN I-Iy1 l-I 3 o,o'-di-CH- 3 O-p-CN-phcnyl - CN benzyl Cli 0,0'-di-CI-1 3 0-p)-CN-phenyI ___CN 1cnzy 1__ LH 0,0'-iC-3 -- N pcy ('-='CN 1-1 0__ 13 o'-di-CI-1 3 0-1)-CN\-phenyl _______________ _____________ CI_13 o'o'-(1i-C1- 3 0-p-CN-phcnyI CI-I=(:I-ICN I-I (:-11 o,o'-di-CI1 3 0-p C-heny CI-LC-(I-ICN IcnzI ClII o,o'-di-CH- 3 O- -CN-phenyl CIICCN bcnzy c H o, o -di-C 1-1 3 -p-C N-ph ny I C N I-Iz Cl-I3 o~o -di-CI-1 3 -Lp-CN-phcnyl C bcnzyL_ I I o,o'-di-CI-1 3 -P-CN-phcnyl _ CN H I I (0,0'-di-C [1 3 -p?-CN-phecny I C I-1-C I-I CN 1__ -I Cl-I 3 0.0 '-tdi-CH- 3 -p-CN-hen I Ci-VC(,I-ICN benzyl CI 3 h _ (00 '-(i-C I-1 3 -p-C.'N-phcnyl __ Cl-l= 'I-1ICN HclI-I 0 .0 '-di-CI-I-p-C-ChCn)-he IC N ------ o. o'-diCH-1 3 O-/)-(CI-I=C 11CI\)-phcny I CI-C N ez' I.9 . o,o'-diCH- 3 O- ,-(CI 1=CI-ICN)-phcnyl C-C IICN'H 1_1_ . 4-cycl propylnaphth-I-yI _____ ____--.-. C \NRPonhblIlxC(G' i' i DOC-2''5L "'2M2 - 102 Ar V W Z 4-cyclopropy1naphth-1-yl _CN benzyl 4-cyclopropyinaphth-1-yi CI I=CHCN H F 4-cyclopropylnaphth-I-yl CI-CI-ICN benzylI F o,o'-di-CI- 3 0-p-CN-phenyl CN -1 o,o'-di-CI-1 3 0-p-CN-phenyl CN benzl F o,o'-di-CHl- 3 0-p-CN-phcnyl CI-=C-ICN o,o'-di-CIHI 3 0-p-CN-phenyl CI=CH-ICN -benzyl F o,o'-di-CIrI 3 -p-CN-phenyl CN -F o,o'-di-CIrI 3 -p-CN-phenyl CN benzyl o,o'-di-CI- 3 -p-CN-phenyl CI-=C-ICN -1 0,0'-di-CrI- 3 -p-CN-phenyl C I=C HCN benzy__ o,o'-diCI 3 O-p-(CI-I=CI-ICN)-phcnyI SO 2 NIH 2 -1 CII o,o'-diCH 3 0-p-(C=I-CHCN)-phenyl SO 2 NII2 benzyl C b 0,0'-iC 3 0-p-(CH=CHCN)-phenyl SO 2 NI-b benzyl __ 0,0o'-diCH- 3 0-p-(C-H=CH-CN)-phenyl SO 2 NH12 H- H~ o~o'-dCH-0-p-(CH=CHCN)-phcnyl SO 2 NH 2 11 C:l o,o'-diCI- 3 0-p-(CH=CI ICN)-phenyl F benzyl C.b ,0 '-dCH 3 0-p-(CII=CHCN)-phcnyl F henzyl I -I oo'-diCH 3 O-p-(CH=CHCN)-phenyl F H 1- H 4-cyclopropy naphth--y _ SO 2 NI- 2 -1 Cib 4-cyclopropyinaphith--l SO 2 NI- 2 bcnzyl CH 4-cyclopopyinaphth-I-yi SO 2 N H-2 benzyl -1 4-cyclopropyInaphth-I-y1 SO 2 NIH 2 -1 H 4-cyclopropyInaphth-I-y I F-___1 H _ C1b 4-cyclopropynaphth-I-yl F benzyl (-I__ 4-cyclopropyinaphth-l-yl F bcnzyl II 4-cyclopropylnaphth-I-y IF -1 I-I o,o'-di-CII 3 0-p-CN-phenyl SO2N H2 -I C_1_ CH-I o,o'-di-CIHI 3 0-p-CN-phenyl SO 2 N H-12 benzyl C1 3 o,o'-di-CH 3 O-p-CN-phcnyl SO 2 NII2 bcnzyl H 0,0'-di-CI-bO-p-CN-phcnyl SO 2 NH 2 o o'-di-CH- 3 0-p-CN-phenyl F -I CH, 0,0 '-di-CH11 3 0-p-CN-phcnyl F bcnzyl Cl 3 0, o '-di-CIH1 3 0-p-CN-phcnyl F benzy'I _l -1 oo'-di-CHII30-p-CN-phcnyl - - -F I I -H. oW'-C/i-CI 3 p-CN-phenyl SO;NI I H1 CI o,o'-di-CI 3 -p-CN-phenyl ___ SON H2 benzyl Cb o.o'-di-CIIrp-CN-phcnyl SO 2 NIH 2 bcn l. II 0.0'-di-C-- 1 -CN-phcnyl SONH2 11 11 o.o'-di-CII 3 -p-CN-phcnyl _-F _II - CI o.o'-di-CIrI 3 -p-CN-phcnyl F ___ bcnzyl clII 0,'-C/i-CI- 3 -p-CN-phcnyl F bcnzyI II o,o'-di-CIrI 3 -p-CN-phcnyl F -I -I oo'-diC-1 3 0-p-(CI-=CICN)-phenyl SO 2 N H-1 2 - 1F o,o'-diC-30-p-(CH=CI-ICN)-pienyl SO 2 NHI-2 bnzyl F_ o,o'-diCI- 3 0-p-(C-=CI-ICN)-phenyl F bcnzyl o,o'-diC1 3 0-p-(CH =CI-I CN)-phcnyI F -1 4-cyclopropyinaphth-I-yi SO 2 NI1 2 H F - 103 Ar V W Z 4-cyclopropylnaphth-l-yl SO 2 NI-1 2 bcnzyl F 4-cyclopropyInaphth-1-yl __ Fn HE 4-cyclopropyinaphth-l-yL F benzyl F o,o'-di-C I-1 3 0-p-CN-phenyl SO2_N H_12 HF o,o'-di-CI-1 3 0-p-CN-phenyl SO2NJH 2 bcnzyl o,o'-di-C H 3 0-p-CN-phenyl F H1 oo'-di-C H 30-p-CN -phenyl I benzylF o o'-di-C 3 -p-CN -phenyl SO 2 N H 2 H o o'-di-CH- 3 N-pihenyl __ ____SO 2 NH 2 benzy F o, o'-di-Cl-p-CN-phel H_ oo'-di-CH 3 -p-CN-phcnyl F- hcnzvl _ : 2,4,6-trimethylpheIyl___ -_ CN - C.j 2.4,6-trimethyl phenyl CN henzvl CI1 2,4,6-trimethyl phenyl CN benzyl 1 2,4,6-trimiethyl phenyl CN -I H1 2,4,6-trinethyl phenyl CI-=CHCN -1 C13 2,4,6-trimethyl phenyl CI-=CI-ICN benzyl - CH 3 4-cyclopropyl phenyl CI-H=C-ICN benzyl - _ 4-cyclopropyl phenyl CI-=CI-ICN -1 1 H 4-cyclopropyl phny_ CN H1 F. 4-cyclopropyl phenyl CN bcnzyl _I 4-cyclopropyl phenyl CH=CHC -I H 2,4,6-trimethyl phcnyl CI-I=C-CCN bcnzyl F_ 2,4,6-trinethyl phenyl SO 2 N- 2 - C 2,4,6-trinethyl phenyl SO 2 N-[ 2 benzyl CH 2,4,6-trinethyl phenyl SO 2 N -1 2 benzyl H-1 2,4,6-trimethyl phenyl SO2N_H_ H_1 -1 2,4,6-trimethyl phy F -I C-13 2.4,6-trinethyl phenyl | F bcnzvl CH11 3 2.4,6-trimethylphienyl | F bcnzyl H 2,4,6-trimethyl phenyl F __1 11 2.4,6-trinethyl phenyl SO 2 N-12 _I F 2,4.6-trimethylphenyl SO 2 NH benzy F 2,4,6-trimethyl phenyl bnzv 2,4,6-trinethyl phenyl F benzyl F 2,4,6-trimnethyl phenyl CN H CI13 2,4,6-trimethyl phenyl CN bcnzyl C- 3 2,4,6-trimethyl phenyl CN benzy H 2,4,6-trimethyl phenyl CN -C -1 2,4,6-trimethyl phenyl CI-=C-ICN H-I CI 3 2,4,6-trimethyl phenyl CI-I=CI-ICN benzyl Cl1 2,4,6-trimethyl phenyl CI-=C-ICN benzy H 2,4,6-trinethyl phenyl CH=CHCN 2,4,6-trinethyl phenyl CN _ b nzyl F-. 2,4,6-trinethy Iphenyl C-=CI-ICN 2,4,6-trimethy phenyl __ CI-I=CHCN bcnzyl F: oo'-dimcthyl-p-cyclopropyl phenyl -. SO 2 N ____ -____ - Cl1 C kNRF'nbiI)CC\S(CU04 107 1 TOC-21M,u112 - 104 Ar V I o, o'-d imethyl-p-cyc Iopropyjyhnyl SO 2 NH 2 I heniyl I 0,0 -dimethyl-p-cycloprop I phecnyl SC) NI Ihctl o~'dinthic~ppphnISO, N 1 -1, 1 ()o'-dinicthyl-p-ycopropyl pheny'! _ __ I: 1-1 11., o,o'-dirnelhyh--yoppyhclI I bcnzvl I I., o,o'-dirncthp'A1? oyfhn) __ benzyl T 0,0 '-dimethyl-p-cyclopropyl plicnyl I __ ]I o,o'-diirnethyl-lp-cyclopropyl phieny! _ SO-)N1 I ___ -I____ o,o'-diirncthyl-p)-cyclopropyl phenyl SO )NI-I- -- benz)'! 1:___ o,o'-dirnethyl-p-cyclopropyl phenlyl 1- 1___ H1-., __ o,o'-dirnethyl-p)-cyclopropyl pheny I I benzyI ___ o,o'-diCII1 3 0-P-(CIVZ=CI-ICN)-phenyl __________1_C-I _ I13 0,W%iCII 3 )-P-(C I=CI-ICN)-picny! CIN -cyc lopropyl CH, - 0,0 -diCI-1 3 0-p--(C[VICI-ICN)-phcny I -- _______ cyclopropyl H 0,0'-diCI-1 3 0-p)-(CHI=CI-ICN)-plicniyl CN Cl-I 3 H 0,0'-diCI-1 3 0-P-(CI-I=CI-ICN)-phcnylI CI-I=CI-ICN Cl-I 3 CI-I 3 0,0 '-dCI-1 3 0-p3-(CI-V=CI-ICN)-plicny I CI-1=C1-ICN cyclopropvl Cl-1 3 _ 0,0'-diCI-1 3 0-P-(CI-I=CI-ICN)-phliy CI-V=CI-ICN cyclop (pyI I I 0,0 ~ ~ ~ ) '-iIIOp(C-C-Qjhnyl Cl-I=CI-ICN C (-13 -I -. 4-cyclopropylnaphth-I-yl CN Cl-I 3 01-13 4 -N lopc~p~yI __ ____ 4yLop yn iphtli-1-yl CN cvcIopopyI [1 _ _ _ _ - 4 - c y c lo p r o p y l n a th -I-y l _ _ I _ _ C N _ _ _ _ ( 1 1 3I I 4-cyclopropyhtiaplitlh-I-y CI PCHCN CH 3 1 (113.I _____ 4-cyclopropyInaplith-I-yl~___ CCIIN elopplCI 4 -cyclIo prop I naplith- I-y I C-=ICN cylo p ropvl 4-cyclopropy nap ith-I-yl (CI-VCI-ICN - (-13 _ o'I-d 3 0-1p-CN-pheny I CN C13C 1I1 o, o'-di-C 1-1 3 0-p-C N-phcnyl I CN cyc In ropyl __ -~ o, o -di-C 1-1 3 0Tp-CN-pheny I_ C N c Y-co pyl x __ -I o,()'-di-C[I1 3 0-p-CN-phenyl____ CN C-13 11I. 0,0 '-di-Cf-1 3 0-p-CN-phenyl ______ I-I=CI-ICN C:-13 . C- oW'-di-CI-I 3 0-p-CN-phclnyi __ CI-h-CI-ICN -cycloprop I Cl-I 3 0,0 '-d-CI-1 3 0-p-CN-phcnyl ____ CI-I=CI-ICN_ cyclopropyl I-I o,0 '-di-CH- 3 O- -CN-plienyl CI-V-C'I-ICN_- C 1-13 I I o,o'-di-CI-1 3 -P-CN-phienyl CN Cl-I 3 Cl-13 0,0'-(li-C I-I 3 -p)-CN-pheny I CN cycloEM)yI (1 o,o'-di-CI-1 3 -p-CN-phcnyI CN cyvclOpromyl II1 o,0'-di-CI-3)1-CN-plienl -__ CN (A113 II ____ o~o -di-CI-1 3 -p)-CN-plicnI Cl l'-=C1-ICN (11C I.; 0.0'-di-Cl-1 3 -p1-CN-pj n I C I h=CI ICN q orm l o,o'-di-CI-I 3 - 1 )-CN-phcnyI C I I=(:I-ICN cyclopi opyI I_ I o,o'-di-;I1 3 -)-_1JplcV C C-C I, - I ___I 0,0~d~lI 3 ~/~(I-VzCl-ICN)-p i\ I___ CNCI (0.0'-diCl 1 3 (-)-(CI-I=CI-ICN)-phcnl C CN cy clopropyl I 0,01-diI 3 -)(C-=IC)-picflyI CI lI -=CIICN cvclo rop)'l - o, o'-diC I 1 3 0-p)-(C'I-I=C1-1 CNJ)-plcl Cl=-IN C__ (I ___ 4 -cyc lopropy Inaphl h- I-yI _I CN (IC I-1 C NR~onbbCCCGICIlI'? ) DC-2'INII - 105 Ar V W Z 4-cyclopropyInaphth-1-yI CN cy'clopropyl 4-cyclopropylnapht--yl ____CI=C-ICN Cl b I_ 4-cyclopropylnaphth-l CH=CHCN cyclopropyl F o,o'-di-CIHI 3 0-p-CN-phcnyl CN CI 3 o,o'-di-CI-30-p-CN-phcny I CN cyclopropyl F 0(o'-di-C-1 3 0-p-CN-phenyl CH=C-CN CH 3 F o,o'-di-CH 1 3 0-p-CN-phenyl C-=CIICN cyclopropyl _ o,o'-di-Cl-r-p-CN-phenyl_ CN Cl 3 F o,o'-di-CI- 3 -p-CN-phcnyl CN cyclopropl F o,o'-di-CIr1 3 -p-CN-phcnyl CH=CHCN C- 3 oo'-di-CIr1 3 -p-CN-phenyI CH=CHCN cyclop F o,o'-diC-1 3 0-p-(C-l=C-ICN)-pheny I _SO 2 NH 2 CH 3 C1b o ,o'-diC-130-p-(C-1=C-1CN)-phenyI SO 2 N 112 ccopp C 1 o0o'-diCI-H 3 0-p-(C H=CIH CN)-phenl SO 2 NI 2 cyclopropy II oo'-diCI 3 0-p-(CI I=CI-ICN)-phcnvl SO 2 NH+-2 _H3 I I o.o'-diCH-l 3 O-p-(CH=CI-ICN)-phclyI SON-__ Cl-1 c, I I o,o'-diCH- 3 0-jp-(CHL=CIHlCN- phenl p cyclopro CI oo'-diCH30-p)-(CH-l=Cl ICN)-phenyl F cycloprop 0,o'-diCI1 3 0-p)-(CI-=CHCN)-phcnyl ___-C 4-cycl -opynaphth-l-vl SO 2 NH2 -1 CH" CH I; 4-cyclo ropylinaphth-1-yl SO 2 Nl I, cyclopropyl CI1; 4-cyclopropylnaphth-1-yl SO 2 NH- 2 cyclopropyl_ I 4-cyclopropylnaphth--yi SO 2 NH2 Cl- 3 __ j 4-cyclopropyinaphth-kIyl F CH3 I 4-cyclopropylnaphth-I-yI F cyclopropyl CH3 4-cyclopropylnaphith-l-yl F cyclopropyl H__ 4-cyclopropylnaphth-1-yl F C-1 3 H_ o,o'-di-CI 1 3 0-p-CN-phcnyl SO 2 NH 2 C-13 CH o,o'-di-CIH 3 0-p-CN-phcnyl SO 2 NH 2 cyclopropyl C1 b o,o'-di-CIHI 3 0-p-CN-phenyl SO 2 NI-1 2 cyclopropyl -1 o,o'-di-CH30-p-CN-phenyl SO 2 1NH12 CH_13 II__ o,o'-di-Cl 1 3 0-p-CN-phenyl F Cl- C II 0,o'-di-CH 3 0-p-CN-phenyl I F cvcloropyp'l CH-I. 3 0,o '-di-CHII 3 0-p-CN-phny~ F cyclopropy H o,o'-di-CH30-p-CN-pheny F CH3 H1 0.0'-di-CI-H3-p-CN-phenyl SO 2 N H1 Clc 3 bIC S ,o'-di1-C N-pheny SO 2 NlH__ c yclopropyl CI b 0,0'-di-CI 3 1p-CN-pyl SO2NH cclopl -11 '-di-Cr-CN-pe nyl SO 2 N H 2 C 3 _ o,o'-di-CI-1 3 p-CN-phlyI _____ '113 C C I 0,0'-di-C I-r p-CN-phenyl _____ cyclopropy C o,o'-di-CI-Hrp-CN-phenyl -F cvclopropy HI o,0o'-di-Cr-1 3 -p-CN-phenyI F H (:1-13 11 o,o'-diCH 3 0-p-(CH=CI-ICN)-phelI SO 2 NH,2 C-I 3 F o,o'-/iC-1 3 0-p-(CI-=CI-ICN)-phcnvl SO 2 NI 2 cyclopropy F o,o'-diC-1 3 0-p-(CI-=CHCN)-phcnyl F cycloprop F o,o'-diC-1 3 0-p-(CH=CI-ICN)-phcnyl FCl H: 4-cyclopropyInaphth--yI SO 2 N -2 Cl-I 3 F_ CNRPorhIDCC\SCGU 0 1 .1-7 1X)C.2,"I"" II - 106 Ar V W Z 4-cyclopropyInaphth-1-yI SO 2 N-1 2 cycIopropyl I' 4-cyclopropyInaphth-1-y F CH13F 4-cyclopropylnaphth-l-yl F cyclopropyl F o,o'-di-CH 3 0-p-CN-phenyl SO 2 N H-12 CIH 3 o,o'-di-CH-130-p-CN-phenyl SO 2 N-12 __cycloproFpy o,0'-di-CI-30-p-CN-phenyl F C-I 3 a,o'-di-CIH-30-p-CN-phcnyl F cyclopropyl o,o'-di-CI--p-CN-phenyl SO 2 NH 2 C-I 3 o,o'-di-C- 3 -p-CN-phenyl SO-NH2 _cclopcOPl o,o'-di-C- 3 -p-CN-phcnyl CH'13 o,o'-di-CHy-p-CN-phcnyl cyclopropy . 4-cyclopoy pheyA CNCIC 4-cyclopropyl pheny CN cyclopropyl ( I 2,4,6-trimethyliphenyl CN cycloproyl 11 2,4,6-trincthyl phenyl CN Cl- 3 II 2,4,6-trinethyl phenyl Cl-Cl=lCH CN C-3 Cl b 2,4,6-trimethyl phenyl C-=CCl-lN cyclopropyl C- 3 2,4,6-trimethyl phenyl CI-=CI-ICN cyclopropyl -1 2,4,6-trinethyl phenyl C-I=CI-ICN Cl-I 3 H 2,4,6-trimethyl phenyl CN C-I 3 ___ 2,4,6-trimethyl phenyl CN cyclopropyl I 2,4,6-trinethyl phenyl CI-=CI-ICN C-1 3 F: 2,4,6-trinethyl phenyl CI-=CI-ICN cyclopropyl _ F 2,4,6-trim-ethyl phenyl SO 2 N-I 2 C1-13 c 2,4,6-trinethyl phenyl SO2NH2 - cyclopropyl CIlI 2,4,6-trinethyl phenyl SO 2 N-I 2 -- cyclopropyl H-I 2.4,6-trinethylphcnyl SO 2 NH 2 Cl 3 1j 2,4,6-trimethyl phenyl F CH3 CH3 2,4.6-trimethyl phenyl F_ cyclopropvl CH 2.4,6-trimethyl pheny l F cyclopropyl H-I 2.4,6-trimethyl phCnVl F Cl-3 4-cyclopropyl phenyl SO 2 NI 1 C-( b -11 4-cycloprop Iphnyl SO 2 NI c c\,loplopI-l 4-cyclopropyl phcnyl F C- 3 4-cyclopropyl phenyl F cycoropy _F 2,4,6-trimnethyl phenyl CN Cl-I 3 Cl- 3 2,4,6-trimethyl phenyl CN cyclopropyl C 13 o,o'-dinethyl-p-cyclopropyl phenyl CN cyclopropyl -1 oo'-dincthyl-p-cyclopropyl phenyl CN CH] 3 _I_ o,o'-dimethyl-p-cyclopropyl phenyl CI-=CI-ICN Cl- 3 CH 1 o,o'-dinethyl-p-cyclopropyl phenyl CI-I=CH-ICN cyclopropyl C3 o,o'-dirncthyl-pc lopropyl pheny C=CHl-I-ICN cyclopropyl H o,o'-dimethyl-p-cyclopropyl phcnyl C-l=CHI-ICN C-I 3 o,o'-dirnethyl-p-cyclopropyl phnyl CN C-I 3 F o,o'-dimethyl-p-cyclopropy phenyl CN cyclopropyl F o,o'-dimethyl-p-cyclopropyl phnyl CI-=CI-ICN C- 3 0.o'-dinethyl-p-cyclopropyl phenyl CI=CI-ICN cyclopropyl F o,o'-dimcthyl-p-cyciopropylphenyl SO 2 ,NI- 2 _ _- Cl C -H3 CINKPoflhrD.I)CSCG-I4 4I',71 I X)C.21,0/2.'I2 - 107 Ar V W Z o~o -diirncthyl-p)-cyclopropyl phcnyt__ -SNl cycLOopyL (II-1 o,o'-dim-cthyl-p)-cyclopropyl phenyl - SO, 2 NI-1 2 1-1oroy II _ o,o'-dirnethyfrj 1 )cp yphfy __- SO 2 ,Nl 11C- 3 _ IL______ _______o Cl-1 3 0.0 '-dimetlhyl-p)cycloprojpylphenyl . .. - -- (11 . o,o'-dir-nctiyL-pjjclopr-opypLyhcnyl -- F-__cyclopropyl} C I-, o,o'-dinicihyl-p-cclp op ylpcnl __ cyclo(ppyl I II o,o'-dirnchyt-pjcI ropyl phcnyl I _____ ("II; I I 2.4.6-tii-nthyl phenyl SO 2 ,NI1 2 Cl]1 3 1 2,4,6-trirncthyl phecnyl SON l-l, cy.clopropl ___ 2,4,6-trim-ethylpey Cl-I 3 F 2,4,6-trimcthyI phenyl I- cvclopropyl 0,o '-c/i-C l-1 3 -p-accty l-phcny ~ - CN I-I 1II 0,0 %Ii-Cf-1 3 -p-acety l-phcnyl CN Cl-I 3 ___ ___ o,o'-di-CI-1 3 -P-acctYl-phcn) I CN Ii1 C' I o,0o'-di-C I-1 3 -p-accty -pheny I CN Cl-1 3 C_____. 15S. The compound of claim 6 which is a compound of formula IA-4 sclcctcd flrom1 compounds in Table 4: Ar / C- N N, N H-0 IA -4 Ar V WZ o,o'-diCl-1 3 0-P-(CI-V=CI-ICN)-phcnyI CN I-1 0, '-diCI-1 3 0-P-(CH-=CH-CN)-phciiyI C1' Cl-I 3 1-1 o,o %/iC 1-1 3 O-P-(C I=C 11CN~)-phcny I C N F7 Cl-1 3 __ o, o'-diC 1-1 3 0-P-(C 11=C 11CN)-phcny I C N C I ___ __Cl]1 3 o, o-diC 1-1 3 0-P-(C I-V=C 11CN)-pheny I CN 1- .I 0,0 '-C/iCI-1 3 0-P-(C l-I=C l-ICN)-plienyI C I-V=C I-I CN CI 1I -1 0,0'-(dCI-13(-P-(C[VICI-ICN)-phcniyl_ CI-I=CH-CN Br C 1-13 00'-diC-1 3 0-P-(CI-V C 1-1C N)-phe n), -]1-C-C I- -13 4-cyc lopropy Ina phth- I-y I (N I- -I _____4-cycloprojp lnaphth-1-y 'I ___ ('N Cl-1 3 1-1 4-cyclopropylnaphth-1-yl __CN Fl C(I1 ___4-c) lppylnaphth-L-yI__ C 1( IIN CI _1CI 4-cycloproplap -- yl -- _CICHCN __ C113 4cclop Inaphth-I-I ICICN l13I 4-cyclopropyinaplith-1-yl AI lICN F ('11 4-cyjo prop~jhhIy I C-CN__ CIfl.;I (),0 -(i-(C-1 3 0--CN-phclyll ____(N____1r C \NR nblICOSG\I;4x1 _1 C-2>1,21 - 108 Ar V W Z o,o'-di-CH_1 3 0-p-CN-phcnyl CN H H o,o'-di-CI-1 3 0-p-CN-phenyl CN CH_ CH o,o'-di-CH_1 3 0-p-CN-phcnyl CN F C b o,o'-di-CH_1 3 0-p-CN-phcnyl CH=CICN H o,o'-di-CH_30-p-CN-phenyl CH-=CHCN CH-3H o,o'-di-CH-30-p-CN-phenyl C H=CH CN F C1.b o,o'-di-CH 3 0-p-CN-phenyl C-]=CI-ICN Cl CI H1 o,o'-diCI-1 3 0-p-(C[=CHCN)-phenyl CN F CH o,o'-diCH30-p-(CH=CH CN)-phenyl CN Cl (1 o,o'-diCI-1 3 0-p-(CI-=CHCICN)-phenyl CN Cl ___H1-1 oo'-diCI-1 3 0-p-(CH=CIICN)-phel)'l CN F -I 0.o '-diC 1 3 0-p-(C-l=C ICN)-phenyl CN -1 CH-b oCo'-diC-1 3 0-p-(C-I=CI-ICN)-phenyl C-1=C-1CN C-13 CIb oo '-diCl1 3 0-p-(Cl-=C ICN)-phcnyl CH=C IHCN F I oo'-diC-1 3 0-p-(CH=CI-ICN)-phenyl CI=CICN CI I I 4-cyclopropylnaphth-l-yl CN -1 I ethyl 4-cyclopropylnaplth-I-yl ____ CN Cl ethyl 4-cy clopropyinaphth--yl CN F _ I 4-cy clopropyInaphth-I-yl CN_ Cl II 4-cy clopropyInaphth-l-y I ClH=CI-ICN Br cthyl _ 4-cy clopropylnaphth-1-yl CIH=C-ICN -I et hyl 4-cyclopropylnaphth-l-y CI-I=CI-ICN -I _ ___ HI 4-cyclopropylnaphth-1-yl CI-=CHCN C-I 3 II o,o'-di-CHII 3 0-p-CN-phcnyl CN F CH 13 o,o'-di-CH 3 0-p-CN-phenyl CN _ CI C lh o,o'-di-C I- 3 0-p-CN -phnyl CN Cl HI o,o'-di-CH130-p-CN-phenyl CN F HI o,o'-di-CIHI 3 0-p-CN-phenyl CCC -1 3 Cl ClHI 3 o,o'-di-CI-1 3 0-p-CN-phenyl CI-=CICN Br CI 3 o,o'-di-CI30-p-CN-phnyl CIH=C HCN Br -1 o,o'-di-C I 3 0-p-CN-phenyl CI-I=CH CN -I o,o'-diCI-1 3 0-p-(CI-=CHCN)-pheny CN C-13 o, o'-diC H 3 0-p-(C-l=CI-CN)-phenyl C N C-13 benzyl o0o'-diCI-1 3 0-p-(CI-=CIICN)-phenyl CN -I bcnzyl o o'-diCI-1 3 0-p)-(CI-I=CI-ICN)-phcnyl CN ) o'-diCH-p-(CHI=CHCN)-phcnvl __ N C1 _I ) o'-diCH-p--(CHl=CHCN)-phenvl _- C1=CCNC henzyl 0. '-diCl 3 0-p-(CI-=CI-ICN)-phenyl CI I=CI lN H- _ hcniyl 0o 0'diCH 3 0-p-(CH=CHCN)-phenyl Cl I=C-ICN 4-cyclopropylnaphth--yl CN c1 13 4-cy clopropynaphth-l-vi CN C 1 3 bcizyI 4-cyc lopropyinaphth-1-yi CN H hcbenzyl 4-cyclopropyinaphth-1-yi CN -I -1 4-cyclopropylnaphth-1-yl CI-VCI-ICN C-1 3 -I 4-cyclopropylnaphth-1-y_ CI-=C-ICN Cl-I 3 bcnzyl 4-cyclopropylnaphth--y _ CI-I=CI-ICN -I benzvl 4-cyclopropylnaphth-1-yl CI-H=C-ICN -I H1 o,o'-di-CI-1 3 0-p-CN-phenyl CN C H-13 H1 -109 Ar V W Z '0di- IOpCN-phenyl CN __C-1 3 be nzvy o,o'-d-CI-1 3 0-P-CNpey CN __ - bnv o, o'-d-C - 3 O--phen-jyl CN __ 1 I- _____ I o~o'-di-CI-1 3 0-p-CN.-phenyl CIlCCNJ___ C- 3 I o,o'-di-Cl 1 3 -p-CN-phen CI 1=CI*ICN ___ CI13 cz' 0,0 -di-CI-1 3 0-p-CN-phcnyl CII ' -N -Ibcnz\,l ____ ,o'-di-CI-1 3 O-p-CN"-phcnyl _____( FIICN _ [I __- ____o~o'-di-CH- 3 :j--N_-phcnyj _ ___ CN -___CI } 0. 'd-CII --CN-phenyl C____ C -1;-bn.*I o, o'-di-CI-1 3 -/)-CN-PICIIYl ______(N I_ _ _ I b_____ o,0o(-i-l:1-(:)-N- -pt~n -1 (N -- I= -11~ I 1CIN H o,o)'-dIi-CI-3p -CN-phcny CI 13 ( IICNC!z - I o,o'-di-CH1- 3 - i-CN-phiciyl___ -.-CII =CI-ICN CI I3-hn~l_ ___ ,o '-di-(;I-3-p-CN -jhcnylI( CHC I-----czl oo'-dil 3-CI-(-p-C-lC N)-pI (H (CN .- __ 0.0 -d/iCII1 3 0-P-(CI-VCH-CN)-pheniy!- ( N -- .- I- v o,o'-diCIi 3 O)-p-(CH-=CI-ICN)-phCnyI - l 1( IIN I- hcnIvyI o~o'-diCI-1 3 0- )-(CI-I=Cl CN)-phcnyl ACII (IICN ___F___ hn.' -- 4-cXSjopropy naphth-1-yi __ CN___I ____ I 4-cyclopropyliiaphth-1-yl CN ____ F____ i __ hndv 4-cyc lopropy iiaphth-1-yI Cl-,I-IiCN ____1___ __I 4-cyclopropylnapitli-1-yl CI-I-CI-ICN I-F hcnz\' __o,o'-di-CI-1 3 0-1p-CN-phenyl CN 1- 11 0,0 -di-CI1-1 3 0-p)-CN-phcnyl CN I.' bcnzvl o,o'-di-CI-1 3 0-p-CN-phcny I CI-I=CIICI"J 1: -1 .- d'ti-CI-1 3 0-p)-CNJ-phienyI CI-I=CI ICN [bcnzyl o~'d-I1 3 pC-hn I ____CN _____ - __ 0,__ 0'-di-CHl- 3 -p-C'Nl-PhfI _ CN Fbnv o, o '-/i-C II -3-CN -phieny I C I CI -CN C' N ___o~o'-di-CI -13-1)-C(p' fy' C-PHC A.-l.... 'N cn 0,0 -diCI-13(-IP-(CI'I=C I-K Cfly. _____SON-I CI1 I; I 0.0 '-diCI130~-p-(CIlI=C]-IC'N)-plieiil _ SO'N I1 CII b-..... o.'_-dC~ 3 O -C[CHN)phfll SO 2 N I-I2I-1 benn I ,0 '-diCI- 3 0:-p-(CI-V=CIICN)-phenyl SO 2 N 1 1__- 1 - 1 0, 'C/iC I-1 3 0-p-(C [1C I-ICN)-phenl~v SO 2 N [I, C l. 3 11_____I o,o'-di(CI-1 3 0)-p-(CI-V=CIICN)-phenyl I.,___ CI-I 3 bcnzyl 0, 0 '-&/C 1- 3 -1)-(C I- C 1-1 CN)-ph n y I F- I I - bcnzy I o,o'-diC I-1 3 0-P-(C I-1=C1-ICN )-phcnyl F-. 1I ___ 13_ I-I __ ____4-cyclopropylnaphth-1-yl SO 2 NII (: I3 lI 4-cyclopropylnaphth-1-yl S0 2 N I-12 CI 13 _____benzyl 4-cycl propylnaphth-1-yl SO 2 N 1-l 1- ___ I-I 4-cyclopropyinaphth-1-y I I ClI 3 I 4-cyc lopropyliiaphthl-1- 'I I:_ _____ I b 'I ___4-c vc Iopropy j~ljth-Ly I ____ '___I env ____4-cyc lopropyltiaplh-1-y 1 1-__~Ji- _ -I 0o,0-di-CI-I 3 0- )-CN-pleflyl SO 2 NI1lk __ .Y C NIUR1hmI[DCC\SCC.'4' 3 _1 DOl )C.23/Oi/2011I -110 Ar V W Z o, o'-di-C -1 3 0-p-CN-phenyl SONH 2 CH 3 hnzy 0,0 '-di-CI1 3 0-p-CN-phcnyl SO 2 NI H2 H hny o,_ '-di-CH30-p-CN-pheny I SO 2 NI [ H I I o,o'-di-CI- 3 0-p-CN-phcnyl F ___CH_ ___CI o,o'-d~i-C H130-p-CN-phenyl F0C13 hen zyI o,o'-di-CH 3 0-p-CN-phenyl F ____ benzyl o,o'-di-CI 3 0-p-CN-phnylI H H o, o'-di-CI-1 3 -p-CN-phenyl SO 2 NI 2 CI1 3 __-I o,o'-di-CI- 3 -p-CN-phenyI SO 2 NI-I 2 ClH 3 benzyl o,o'-di-C H 3 -p-CN-phcnyI SO 2 N 12 -1 beng I o,o'-di-CI- 3 -p-CN-phenyl SO 2 N H2 H H o,o'-di-C-I 3 -p-CN-phcnyl F ClI 1-3 o,o'-di-CI-b-rp-CN-phcnyL F CI-1 3 bnzyI o,o'-di-C -1 3 -p-CN-phenyl F -1 -- benzy o,o'-di-C1p 3 -- CN-phenyl F H H1 o,o'-diC-1 3 0-p-(CH=CHCN)-phcny SO 2 N- 2 F -1 o.o'-diCI-1 3 0-p-(CI-=CHCN)-phenyl SO 2 N12 F benzyl o,o'-diC-1 3 0-p-(CI-I=CI-ICN)-phcnyl F -F benzyl oo '-diCI- 3 0-p-(C-I=CI-ICN)-phcny I F F -1 4-cyclopropy naphth-1-y SO 2 N- 2 F -1 4-cyclopropyinaphth-1-yI SO 2 N__ F bcnzyl 4-cyclopropylnaphth-1-yl F F Ij 4-cyclopropyjnaphth-l-yi L_ hcnzyl o,o'-dIi-C-1 3 0-)-CN-phcnyI SO 2 N 1 -I o,o'-di-CH 3 0-p-CNphenyl SO 2 NI i1 e hend y o,o'-di-CHI30-p-CN-phcnyl F o,o'-di-CI-30-p-CN-phcnyI F F bcnvI o,o'-di-CI-1 3 -p-CN-phcnyl SO 2 NH .2 .___ H o,o'-di-CI-1 3 -p-CN-phenyl SO 2 NI-I 2 F henzyl o,o'-di-Cr-1 3 -p-CN-phcnyI F F H o,o'-di-CrI- 3 -p-CN-phcnyI F F benzy 4-cyclopropyl phenyl CN C-I 3 H1 4-cyclopropyl phenyl CN C-I 3 bcnzyl 4-cyclopropyl phenyl CN ___H bcnzyl 2,4,6-trinethyl phenyl CN H H 2,4,6-trimeithyl phenyl CII=C-ICN (113 Hj 2,4.6-trimethyl phcnyL CH=CHCNCH-3 benzyl 2,4,6-trinethyl phenyl CH=CI-ICN H__ benzyIl 2,4,6-trimiethyl phen yl CCCN H-I H 2,4,6-trinethyl phenyl CN F H 2,4,6-trimethyl phenyIl CN F bcnzvI 2.4.6-trimethyl phenyl CH=C-IC N I __I-I 2.4.6-triimncthyl phenyl CH=CI ICN - bel nzyI 2.4.6-trimethyl phenyl SO 2 NH2 CH3 1I 2,4.6-trinethyl phenyl SO 2 NIH 2 C-13 hnl 2,4,6-trinethyl phcnyl SO 2 NH, H henzy 2,4.6-trimethyl phenyl SO 2 NH 2 -1 2,4,6-trimethyl phenyl F1 C H SNR~onbIl~\lW CGuIu4K1,7_ .1OC-'"fl*'II - 111 Ar V W Z 2,4,6-trimethyl phenyl F CH _ benzyl 2,4,6-trimethyl phenyl F I- 1 bcnzyl 2,4,6-trim-ethyl phenyl F H I 2,4,6-trinethyl phenyl SO 2 NH F 2,4,6-trinethyl phenyl SO 2 NH12 F - bcnzvl 4-cyclopropyl phenyl F . H 4-cyclopropyl phenyl F F- hcnzyl 2,4,6-trinethyl phenyl CN (13 1-j 2,4,6-trimethyl phenyl CN CH bcnzyl 2,4,6-trimethyl phenyl CN H-_ benzvl oo'-dimethyl-p-cyclopropyl phenyl CN H- I o0o'-dinethyI-p-cyclopropyl phenyl CHI=CI-ICN (13 H o,o'-dinethyl-p-cyclopropyl phenyl C-I=CI-ICN CH 13benzyI oo'-dimnethyl-p-cyclopropyl yl CI-I=CHCN H benzyl o,o'-dimethyl-p-cyclopropyl phenyl CH=CHCN H o,o'-dirncthyjpjcyclopropyl phenvI CN o.o'-dirnethyl-p-cyclopropylphenyl _CN benyl o.o'-dimethyl-p-cyclopropyl phcnyl_ CIl CI ICN .| '-dimethy-p-cycloprpyphenyl CHCHCN b C I = 1 Cn y o,o'-dirnethy-p-cycoprpylphenyl SO 2 NH1 2 _ CH. 3 II o~o'-dirncthyl-p-cyclopropyl phenyl SO 2 N 11, C-1 3 bcnzyl oo'-dinethyl-p-cyclopropyl phenyl SO 2 N12 H1 benzyl oo'-dirnethyl-p-cyclopropyl phenyl SO 2 NI-2 oo'-dirnethyl-p-cyclopropyl phenyl F C- 3 -I o,o'-dimethyl-p-cyclopropyl phenyl F C- 3 benzyll o,o'-dincthyl-p-cyclopropyl phenyl F H benzyl o,o'-dinethyl-p-cyclopropyl phenyl F 1 H o,o'-dinethyl-p-cyclopropyl phenyl SO 2 NI-1 2 F -1 oo'-dinethyl-p-cyclopropyl phenyl SO 2 N-12 F bcnzy l 2.4,6-trimethyl phenyl F F I-I 2,4,6-trinethyl phenyl F _ _ F benzvl oo'-diC-1 3 0-p-(CI-=CHCN)-pheny CN Cl-I 3 CI-I 0,0'-(diCI130-p)-(CH=CHCN)-phenyl CN C- 3 Cyclo(propvl oo'-diCI- 3 0--(C-=CI-ICN)-phcnyI CN -I eVCopropy'I o,o'-diCH 3 0-p-(C H=C ICN)-phcnyl CN H CH 3 o.o'-diCI- 3 0-p)-(CI-I=Cl-CN)-pheniyi CN C-3 o,o'-diCI-pO- 1 )-(CH=CHCN)-phenyl CH=CHCN cH3 CyOcloprop 0.0 '-d/iC-1 3 0-p-(CH=CI-ICN)-phenyl CH=CHCN H cyclopropyl o, o'-diCI-1 3 0-p-(C I-=CIICN)-phenyl -CH=CIHCN H (C 4-cyclopropyinaphth-l-yl CN -13 _CH3 4-cyclopropyinaphth--yl CN C-13 cyclopropy 4-cyclopropyinaphth-l-yI CN H cyclogrol 4-cyclopropyinaphth--yl CN - Cl-I 3 4-cyclopropylnaphth--yl CI-=Cl-CN Cl-I 3 Cl-3 4-cyclopropyinaphth-1-yl CI-=C-ICN Cl-I 3 cyclopropyl 4-cyclopropylnaphth-1-yl (I-=CI-ICN -1 cyclpopl 4-cyclopropylnaphth-l-yl C=I-VCHCN - (1-13 o,o'-di-CI-1 3 0-p-CN-phenyl CN Cl-I 3 -13 C \NR o,,ihhDICC\SCG~I x1IDC 1 w( 9~52 12 - 112 Ar V W Z o,o'-di-CH 3 -0-p-CN-phenyl CN Cl-3 cyclopropyl o,o'-di-C-1 3 0-p-CN-phenyl _CN __H cyclopropyl o,o'-di-CH 3 0-p-CN-phenyl CN -I C b o,o'-di-CI -1 3 0-p-CN-phenyl CHV=CHCN C H13 C I.-, o,o'-di-CI-1 3 0-p-CN-phenyl CI-=CI-ICN C-1 3 cyclopropyl o,o'-di-CIH 3 0-p-CN-phcnyl C-=CI-ICN -I cvclopropyI o,o'-di-CH-1 3 0-p-CN-phcnyl CH=CI-ICN II C-1 3 0,0'-di-CH 3 -p-CN-phcnyl CN C-13 Cl-H o,o -di-CH 3 -- CN-plhcnyl CN C1-1 - cvclopropyl 0,0'-di-C-1r- 1 CN-phenyl CN H c oryl o,o'-di-CI1 3 -p-CN-phcnyl CN I_ Cb o,o'-di-CH 3 -p-CN-phenyl CI =I-ICN C- ICI b o,o'-di-C-1- 1 -CN-phenyl CH=CI-ICN CH- cyclopropyl oo'-di-C-p-CN-phcnyl CH=CIHCN H cyclopropyl o,o'-di-CIr1 3 -p-CN-phenyl CH-=C HCN C113 o,o'-diC-1 3 0-p-(CI-=CHCN)-pheny CN F C IH o,o'-diCI- 3 0-p-(C-=C I-ICN)-phenyl CN F_ cyclopropyl o,o'-diC-1 3 0-p-(C-1=C-1CN)-phenyl C-=CI-ICN F cyclopropyl o,o'-diCH1 3 0-p-(C H=C-1CN)-phenyl CI-=C-ICN F Cl-I 3 4-cyclopropylnaphth-1-yl CN F Cl-1 3 4-cyclopropylnaphth-l-yl CN F cyclopropyl 4-cyclopropylnaphth-1-yl CI-=Cl-lCN Fc C .- , 4-cyclopropylnaphth-I-y I CI-CHCN F _cyc lopropyl o,o'-di-C H-1 3 0-p-CN -pheny I CN F C -13 o,o'-di-CI-30-p-CN-phcnyl CN F-.- cvclopoppyl o.o'-di-C 1 3 0-p-CN-phcnyl CI-=CI-ICN I C H3 0,0'-Ci-CII 3 0-p-CN-phcnyl CH=CHCN Fcyclopropyl o,o'-di-CIr1 3 -p-CN-phcnyl CN F_ __ _ C13 o,o'-di-CIr1 3 -p-CN-phcnyl CN F_ I c)'clopropyl o,o'-di-C 3 -CN-phenyl Cl l=CIHN F C_ ( o.o'-di-CIr1 3 -p-CN-phcnyl (Hl-=Cl-C(:N cylopropyl o,o'-diCI-pO- 1 /-(C-=CHCN)-phlny SO 2 N I- cb C 1 ; 0,0o'-diCH1 3 0-p-(CI=CICN)-phcnyl SO 2 N CH__3 cyclopropy o.o'-diC-30-p-(CI-=CHCN)-phcnlyl SO 2 NH, H cclop opyl 0,0'-diC-1 3 0-p-(CI-=C-ICN)-phenyl SO 2 NH2 11 C-I 3 _ o,o'-diCI-1 3 0-p-(CH=CHCN)-phcnyl SO 2 N-12 Cl-I 3 C-13 o,o'-diC1 3 0-p-(CI-=CI-ICN)-phcnyl F CI 3 cyclopropyl o,o'-diC-30-p-(CI-=CHCN)-phenyl F -1 cyclopropyl o,o'-diCH 3 0-p-(CI-=CI-ICN)-phenyl F II C-I 3 4-cyclopropyinaphth-1-yl SO 2 NI-1 2 Cl- 3 (-13 4-cyclopropylnaphth-l-yl SO 2 NIH1 2 Cl- 3 cyclopropyl 4-cyclopropylnaphth-l-yl SO 2 NI1 2 H- I -c yclopropyl 4-cyclopropyinaphth-l-yi SO 2 N-F3 -I CI 13 4-cyclopropylnaphth-1-yl F C-I 3 C Ib 4-cyclopropyinaphth-l-yl F C-I 3 cyc lopropyl 4-cyclopropyinaphth-l-yL F - cyclopropyl 4-cyclopropylnaphth-1-yl F H C-13 o,o'-di-CIHI 3 0-p-CN-phenyl SO 2 N-12 c 1-1 CHb L, C \NR'onbhDlCO\SCG,4U 4167_l.DOC-23,/%201J2 -113 Ar V W Z o,o'-di-CH 3 0-p-CN -phenyl SO 2 NHI 2 C 13 cyclopropyl o,o'-di-CH 3 0-p-CN -phenyl SO 2 NI12 -1 cyclopropyl o,o'-di-CH 3 0-pJ-CN-phenyl SONI 11 C1 ( 113 o,o'-di-C1 3 0-p-CN-phenyl C -b Cb o,o'-di-H0--CIl- 3 0-p-CN-phenyl C H elopro o,o'-di-ClH 3 0-p-CN-phenvl H cy coprpp 0, '-di-CI1 3 0- p-CN-phenyl 0,0 -di-CH-p-CN-phenyl S C C o, o'-di-C H rp-CN-phenyl SO 2 NI CI cy clopr op o,o'-di-CI- 3 -p-CN-phcny SO 2 NH2 _H cyclopropyl o, o'-di-CH 3 -p-CN-phenyl SO 2 NHl12 Hy __CH3 o,o'-di-C 11 3 -p-CN-pheny I F Cl-h CI 3 0,0'-di-CI- 3 -p-CN-phenyl F Cl-b cycloprop o,o -di-CI- 3 -p-CN-phcnyl F H cyclopropy! o,o'-di-CI- 3 -p-CN-phenyl F H ClH 3 o,o'-diCI- 3 0-p-(C-=CI-ICN)-phcny SO 2 NH2 F Cl-I 3 oo'-diC-1 3 0-p-(C-l=CI-ICN)-phenyl - SO 2 NH 2 I cyclopoPy o,o'-diCI- 3 0-p-(C-=CIICN)-phenyl I F cyclopropyl o o'-diCH 1 3 0-p-(CH=CICN)-phenyl F I CH 4-cyclopropyInaphth-l-yl SO 2 N 1-1 c 1 4-cyclopropylnaphth-1-yl SO 2 NH 2 11F cyclopropyl 4-cyclopropylnaphth-l-yi F F C- I. 4-cycloropyinaphth-I-yl F F cyclopropyl 0.0'-di-CH0-p-CN-phenyl SO 2 NIH F _ CH __oo-di-C-1 3 0-p-CN-phenyl.. SO 2 NH 2 F lc\'clopropyl o,o'-di-C[H 3 0-p-CN-phenyl F F CHI o,o'-di-C_30-p-CN-phenylF _F cyclopropyl o,o'-di-CI- 3 -p-CN-phenyI SO 2 NI 2 F CH 3 o,o'-di-CI- 3 -p-CN-phcnyl SO 2 NI-1 2 F cyclopropyl o,o'-di-CI- 3 -p-CN-phcnyI F 1F Cl o,o'-di-C1--p-CN-phenyl F F -cyclopropyl 2,4,6-trimethyl phenyl CN C-13 Cl-I 3 2,4,6-trimethIyl phenyl CN Cl-I 3 cyclopropyj 2,4,6-trinethylphenyl CN -I Cyclopropyl 2,4,6-trimethyl phenyl CN H C(13 2,4,6-trimethyl phenyl C-l=CC-ICN Cl-I 3 Cl b1 2,4,6-trirnethyl phenyl CI=CH ICN C13 cycloRopWl 2,4,6-trimethyl phenyl CI-=C-CN H-I cyclopropyl 2,4,6-trinethyl phenyl CI-I=CI-ICN HI C__3 2.4,6-trinethyl phenyl CN FI_ CH-13 2,4,6-trimethjyphenyl CN F_ I cyclopropvl 2.4,6-trinethyl phenyl _____ CH-VCHCN F_ I-1 2,4,6-trinethyl phenyl ClH- CHII CN ----- I __ cyclopropyl 2,4,6-trirncthyl phenyl SO 2 NH: CH___(3 CH 2.4,6-trimethyl phenyl _ I SO 2 NH) 3cyco ropyl 2,4,6-trimethyl phenyl SO;NII _ H lopropyl 2.4.6-trimethylphenl SO 2 _NHp _ _ CH 2.4.6-trinethyl phenyl CH 1. c CI hI_ - 11 4 Ar V W Z 2,4,6-trimethyl phenyl_ F Clb cyclopropy 2,4,6-trimethyl phenyl F - cyclopropyl 2,4,6-trimethyl phenyl F I _ ____ C113 4-cyclopropyl phenyl SO 2 N H2I-- F _Cl- 3 4-cyclopropyl phenyl SO 2 1N1 2 F cyclopropyL 4-cyclopropyl phenyl F F C-13 4-cyclopropyl phenyl F F cyclopropyl o,o'-dimethyl-p-cyclopropyl phenyl CN CH-13 _C13 o,o'-dimethyl-p-cyclopropyl phenyl CN CH3 cyclopropyl o,o'-dimethyl-p-cyclopropyl phenyl CN H-1 cyclopropyl o.o'-dimethylp-yclopropy pyl CN ___ _ CH1 3 o,o'-dirnethyl-p-cyclopropyl phenyl CI-=CI-ICN CH Cl o,o'-dimeicthyl-p-cyclopropyl phenyl CI-=CHFCN CH cyclopropyl o,o'-dimcthyl-p-cyclopropyl phcnvl CH=CHCN I cyclopropyl o,o'-dimcthyl-p-cyclopropyl phenyl CH=CCN -1 Cl I I o.o'-dimcthyl-p-cyclopropyl phcnyl CN F l o.o'-dimethyl-p-cyclopropy plhenyl CN -F cyclopropyl o.o'-dimcthyl-p-cyclopropylpheyl - C I-CHCN F. C I o,o'-dirnethyl-p-cycropyphenl C-1=CI-ICN F - cycloproproyl o.o'-dimethyl-p-cycpmropypheny ___SO 2 NH2 CH113 CHI 3 o,o '-dimethyl-p-cyclopropyl phenyl SO 2 Nll2 CH! 3 cyclopropyl oo'-dimethyl-p-cyclopropyl phenyl SO 2 NI-I 2 - cyc.loprpyl_ o,o -dimethyl-p-cyclopropyl phenyl SO 2 NH 2 H Cl-I o,o'-dinethyl-p-cyclopropyl phenyl F CH3 CH o,o'-dimethyl-p-cyclopropyjl phenyl F CH 3 cyclopropyl o.o'-dimethyl-p-cyclopropyl phenyl F -1 cyc lopropyl oo'-dimethyl-p-cyclopropyl phcnyl F - _ CI b 2,4,6-trimcthyl phenyl SO 2 NIHI 2 F -13 2,4,6-trimethyl phenyl SO 2 NI- 2 F cyclopropyl 2,4,6-trimethyl phenyl F F Cl 13 13 2,4,6-trimethyl phenyl F F __ cyclopropyl_ o,o'-di-CI- 3 -p-acetyl-phenyl CN -1 -I o,0'-di-CI- 3 -p-acetyl-phenyI CN Cl 3 -1 o,o'-di-Cr-1 3 -p-acetyl-phenyl CN -1 Cl o,o'-di-CII 3 -p-acetylpheny CN C1_3 CL. 15. The compound of claim 1. which is selected from: //-NH INN~ N' J N CN O N N N NN N 0 N N H I 0 //-N I1 0 KN N NN ~ N ~ NH~ ~N OH I O N N N Ne N" H 14 14 CN C INN V,IIXhDCSCG0(I I~( I x (10 1 .52 -115 r - C N N I I N N IINN N'; NC N N HI N N N - N /,- N I -C" N -, ONN N CN N O K CN -A N _ ((N N N(N N N 0 N 11N >1 CCN N; N" .'N N N (N? C N oN N N il N N ON 7N NNl I7 N N' C N' F N~ 0 N N ( N '(Y Ni.-1N No ( N N I, N~N N N~ N N" N_( 5'N N N N, N, - N NN HN N N NC) N cI N N NN N N N~r Y ( N :f N N M.0 I, C o N OF <<-*-~. anNd 16. conPOnd acoringto ay oe o'clams to15 Sbstntilly s hrcibefoc dl-hccI