WO2013078413A1

WO2013078413A1 - Modulators of lipid storage

Info

Publication number: WO2013078413A1
Application number: PCT/US2012/066394
Authority: WO
Inventors: Matthew B. Boxer; Mathias BELLER; Kirsten TSCHAPALDA; Min Shen; Li Liu; Yaqin ZHANG; Zhuyin Li; Carole SZTALRYD
Original assignee: The United States Of America, As Represented By The Secretary, Department Of Health And Human Services; Max-Planck-Gesellschaft Zur Foerderung Der Wissenschaften E.V.; University Of Maryland, Baltimore
Priority date: 2011-11-22
Filing date: 2012-11-21
Publication date: 2013-05-30

Abstract

Disclosed are compounds of formulas I, II, and III: Formulas I, II, and III wherein R¹-R¹⁹ and n are as described herein, or pharmaceutically acceptable salts thereof, or an enantiomer thereof or a conjugate thereof wherein the conjugate comprises a marker group, for use in treating or preventing a disease or disorder responsive to reduction of lipid storage droplets in an animal in need thereof. Also disclosed are pharmaceutical compositions comprising such compounds or pharmaceutically acceptable salts thereof and a pharmaceutically acceptable carrier and methods of treating or preventing neurodegenerative diseases and disorders.

Description

MODULATORS OF LIPID STORAGE

CROSS-REFERENCE TO A RELATED APPLICATION

[0001] This patent application claims the benefit of U.S. Provisional Patent Application No. 61/562,894, filed November 22, 2012, which is incorporated by reference.

BACKGROUND OF THE INVENTION

[0002] Storing lipids as a reservoir for energy or anabolism of elementary metabolites is a common feature of life in organisms from bacteria to humans. The evolutionary conserved cellular lipid storage organelle is the so-called lipid storage droplet (LD). Despite their ubiquitous nature, LDs share a simple, stereotyped structure of a hydrophobic core harboring the storage lipids, which is shielded by a droplet-specific phospholipid monolayer to which proteins are attached (Brasaemle, D. L. J. Lipid Res. 2007, 48, 2547-2559). The current model of LD biogenesis involves an incorporation of the lipid core into the membrane leaflets of the endoplasmic reticulum (ER), followed by a subsequent budding-like maturation of an LD, which ultimately pinches off.

[0003] There are a number of lipid storage diseases that are inherited metabolic disorders that result in harmful buildup of various lipids. Most of these diseases, termed lipidoses, are caused by various deficient enzymes such as: glucocerebrosidase (Gaucher disease), a- galactosidase-A (Fabry disease), ceramidase (Farber's disease), β-galactosidase (GM1 gangliosidoses), β-hexosaminidase (Tay-Sachs and Sandhoff disease), galactosylceramidase (Krabbe disease) and arylsulfatase A (metachromatic leukodystrophy) (Gieselmann, V.

Biochimica et Biophysica Acta 1995, 1270, 103-136; Winchester, B.et al. Biochem. Soc. Trans. 2000, 28, 150-154). Lipid droplets are established key components of cellular energy homeostasis that is often altered in obesity and its associated serious health consequences including increased risk for hypertension, insulin resistance, diabetes and coronary heart disease. An important clue to the pathogenesis of these metabolic diseases is the presence of ectopic lipid droplets (LDs) in liver, skeletal, heart muscle of patients with "metabolic syndrome" and presence of LDs have been associated to tissue lipotoxicity and dysfunction. However, presence of LDs in oxidative tissues is also observed in un-harmful physiological conditions, such as at times when cellular energy needs and energy production from mitochondria fatty acid (FA) β-oxidation are high (fasting, endurance exercise). Hence, it is clear that development of tissue lipotoxicity and dysfunction is not simply due to the presence of LD in non-adipose tissues but due at least in part to alterations in LD function.

[0004] There is an unmet need for small molecules that can regulate the storage of LDs and can therefore be used as therapeutics to prevent or treat these disorders.

BRIEF SUMMARY OF THE INVENTION The invention provides a compound of formula I, II, or III:

wherein:

R¹ is selected from alkyl, aryl, arylalkyl, and alkylaryl, each of which is optionally substituted with one or more substituents selected from halo, alkyl, hydroxy, carboxy, phosphoryl, phosphonyl, phosphono alkyl, carboxy alkyl, dicarboxy alkyl, dicarboxy haloalkyl, sulfonyl, cyano, nitro, alkoxy, alkylthio, acyl, acyloxy, thioacyl, acylthio, aryloxy, amino, aminoalkyl, alkylamino, dialkylamino, trialkylamino, guanidino, aminocarbonyl, aldehydo, and ureido;

R² is selected from heterocyclyl, heteroaryl, cycloalkyl, dimethylamino alkyl, and benzyl, each of which is optionally substituted with one or more substituents selected from halo, hydroxy, carboxy, phosphoryl, phosphonyl, phosphono alkyl, carboxy alkyl, dicarboxy alkyl, dicarboxy haloalkyl, sulfonyl, cyano, nitro, alkoxy, alkylthio, acyl, acyloxy, thioacyl, acylthio, aryloxy, amino, aminoalkyl, alkylamino, dialkylamino, trialkylamino, guanidino,

aminocarbonyl, aldehydo, and ureido;

R³ and R⁴ are each independently a lower alkyl or, taken together with the carbon atom to which they are attached, form a 5- to 7-membered ring;

R¹⁰ is selected from alkyl, dialkylaminoalkyl, heterocyclyl, heteroaryl, aryl, arylalkyl, arylcycloalkyl, and each of which is optionally substituted with one or more substituents selected from alkyl, halo, cycloalkyl, aryl, fused aryl, fused cyclic, arylalkyl, and

arylcarbonyl;

R", R¹², R¹³, and R¹⁴ are independently hydrogen or alkyl;

R° and R' are independently hydrogen,lower alkyl, or arylalkyloxyalkyl, or, taken together with the carbon atom to which they are bonded, form a 5-7 membered ring;

R is H or a substituent selected from halo, alkyl, monohalo alkyl, dihaloalkyl, trihaloalkyl, monohalo alkoxy, dihalo alkoxy, trihalo alkoxy, hydroxy, carboxy, phosphoryl, phosphonyl, phosphono alkyl, carboxy alkyl, dicarboxy alkyl, dicarboxy haloalkyl, sulfonyl, cyano, nitro, alkoxy, alkoxy carbonyl, heterocyclyl, alkyl heterocyclyl, heterocyclylalkyl, alkylthio, acyl, acyloxy, thioacyl, acylthio, aryloxy, amino, aminoalkyl, alkylamino, dialkylamino,

trialkylamino, guanidino, aminocarbonyl, aldehydo, and ureido; wherein two or more R substituents can form a fused ring with the phenyl ring to which they are attached;

R⁹ is H, OR¹⁵, or NR^I6R¹⁷; wherein R¹⁵, R¹⁶, and R¹⁷, are independently hydrogen or lower alkyl;

R is hydrogen or lower alkyl;

R¹⁹ is hydrogen or halo;

A is NH(CH₂)_m, CH₂, or a bond; m is 0 or 1 ; n is 1 -5; and p is 0-3; a pharmaceutically acceptable salt thereof, or an enantiomer thereof; or a conjugate thereof wherein the conjugate comprises a marker group.

[0006] The invention also provides a method of preventing or treating a disease or disorder responsive to reduction of lipid storage droplets in an animal in need thereof comprising administering an effective amount of a compound of formula I, II, or III or a combination thereof:

wherein:

R is selected from alkyl, aryl, arylalkyl, and alkylaryl, each of which is optionally substituted with one or more substituents selected from halo, alkyl, hydroxy, carboxy, phosphoryl, phosphonyl, phosphono alkyl, carboxy alkyl, dicarboxy alkyl, dicarboxy haloalkyl, sulfonyl, cyano, nitro, alkoxy, alkylthio, acyl, acyloxy, thioacyl, acylthio, aryloxy, amino, aminoalkyl, alkylamino, dialkylamino, trialkylamino, guanidino, aminocarbonyl, aldehydo, and ureido;

aminocarbonyl, aldehydo, and ureido;

arylcarbonyl;

R^{1 1}, R¹², R¹³, and R¹⁴ are independently hydro gen or alkyl;

R⁶ and R⁷ are independently hydrogen,lower alkyl, or arylalkyloxyalkyl, or, taken together with the carbon atom to which they are bonded, form a 5-7 membered ring;

R⁸ is H or a substituent selected from halo, alkyl, monohalo alkyl, dihaloalkyl, trihaloalkyl, monohalo alkoxy, dihalo alkoxy, trihalo alkoxy, hydroxy, carboxy, phosphoryl, phosphonyl, phosphono alkyl, carboxy alkyl, dicarboxy alkyl, dicarboxy haloalkyl, sulfonyl, cyano, nitro, alkoxy, alkoxy carbonyl, heterocyclyl, alkyl heterocyclyl, heterocyclylalkyl, alkylthio, acyl, acyloxy, thioacyl, acylthio, aryloxy, amino, aminoalkyl, alkylamino, dialkylamino,

R⁹ is H, OR¹⁵, or NR¹⁶R¹⁷; wherein R¹⁵, R¹⁶, and R¹⁷, are independently hydrogen or lower alkyl;

R is hydrogen or lower alkyl;

R¹⁹ is hydrogen or halo;

A is NH(CH₂)m, CH₂, or a bond;

m is 0 or 1 ; n is 1-5; and p is 0-3; a pharmaceutically acceptable salt thereof, or an enantiomer thereof.

[0007] The invention additionally provides a method of identifying a molecular target involved in lipid storage in a cell, comprising contacting the cell with a compound of formula I, II, or III:

wherein:

aminocarbonyl, aldehydo, and ureido;

arylcarbonyl;

R^U, R¹², R¹³, and R¹⁴ are independently hydrogen or alkyl;

R⁹ is H, OR¹⁵, or NR^{I 6}R¹⁷; wherein R¹⁵, R¹⁶, and R¹⁷, are independently hydrogen or lower alkyl;

R is hydrogen or lower alkyl;

R¹⁹ is hydrogen or halo;

A is NH(CH₂)m, CH₂, or a bond; m is 0 or 1 ; n is 1 -5; and p is 0-3; a pharmaceutically acceptable salt thereof, or an enantiomer thereof; or a conjugate thereof wherein the conjugate comprises a marker group; to form a complex of the target and the compound, pharmaceutically acceptable salt thereof, or an enantiomer thereof; and detecting the presence of complex of the target and the compound in the cell, wherein the presence of the complex indicates the presence of the molecular target in the cell.

[0008] The invention further provides a method of identifying a molecular target involved in lipid storage in a cell, comprising contacting the cell with a compound of formula I, II, or III:

I II III

wherein:

R² is selected from heterocyclyl, heteroaryl, cycloalky], dimethylamino alkyl, and benzyl, each of which is optionally substituted with one or more substituents selected from halo, hydroxy, carboxy, phosphoryl, phosphonyl, phosphono alkyl, carboxy alkyl, dicarboxy alkyl, dicarboxy haloalkyl, sulfonyl, cyano, nitro, alkoxy, alkylthio, acyl, acyloxy, thioacyl, acylthio, aryloxy, amino, aminoalkyl, alkylamino, dialkylamino, trialkylamino, guanidino, aminocarbonyl, aldehydo, and ureido;

arylcarbonyl;

R^H, R¹², R¹³, and R¹⁴ are independently hydrogen or alkyl;

R is hydrogen or lower alkyl;

R¹⁹ is hydrogen or halo;

A is NH(CH₂)_m, CH₂, or a bond; m is 0 or 1 ; n is 1 -5; and a pharmaceutically acceptable salt thereof, or an enantiomer thereof; or a conjugate thereof wherein the conjugate comprises a marker group; and determining a change in an activity of the molecular target, wherein the change in the activity of the molecular target indicates the activity of the molecular target in lipid storage in the cell.

BRIEF DESCRIPTION OF THE SEVERAL VIEWS OF THE DRAWING(S) [0009] The Figure depicts several embodiments of the invention.

DETAILED DESCRIPTION OF THE INVENTION [0010] In an embodiment, the invention provides compound of formula I, II, or III:

I II III

wherein:

R¹ is selected from alkyl, alkenyl, aryl, arylalkyl, and alkylaryl, each of which is optionally substituted with one or more substituents selected from halo, alkyl, hydroxy, hydroxyalkyl, carboxy, phosphoryl, phosphonyl, phosphono alkyl, carboxy alkyl, dicarboxy alkyl, dicarboxy haloalkyl, sulfonyl, cyano, nitro, alkoxy, trifluoroalkyl, trifluoroalkoxy, alkylthio, acyl, acyloxy, thioacyl, acylthio, aryloxy, amino, aminoalkyl, alkylamino, dialkylamino, trialkylamino, guanidino, aminocarbonyl, aldehydo, optionally protected aminopolyalkoxy, and ureido;

R is selected from heterocyclyl, heteroaryl, cycloalkyl, dimethylamino alkyl,

(trifluoromethyl)-3H-diazirin-3-yl), and benzyl, each of which is optionally substituted with one or more substituents selected from halo, hydroxy, carboxy, phosphoryl, phosphonyl, phosphono alkyl, carboxy alkyl, dicarboxy alkyl, dicarboxy haloalkyl, sulfonyl, cyano, nitro, alkoxy, alkylthio, acyl, acyloxy, thioacyl, acylthio, aryloxy, amino, aminoalkyl, alkylamino, dialkylamino, trialkylamino, guanidino, aminocarbonyl, aldehydo, and ureido;

R³ and R⁴ are each independently a lower alkyl or, taken together with the carbon atom to which they are attached, form a 5- to 7-membered ring; R¹⁰ is selected from alkyl, dialkylaminoalkyl, heterocyclyl, heteroaryl, heteroarylalkyl, aryl, arylalkyl, (3-(trifluoromethyl)-3H-diazirin-3-yl), arylcycloalkyl, and each of which is optionally substituted with one or more substituents selected from alkyl, alkenyl, halo, cycloalkyl, aryl, fused aryl, fused cyclic, arylalkyl, heteroarylalkyl, and arylcarbonyl;

R^{1 1} , R¹², R¹³, and R¹⁴ are independently hydrogen or alkyl;

R⁶ and R⁷ are independently hydrogen,lower alkyl, or arylalkyloxyalkyl, or, taken together with the carbon atom to which they are bonded, form a 3-7 membered ring;

R¹⁸ is hydrogen or lower alkyl;

R¹⁹ is hydrogen or halo;

A is NH(CH₂)_m, CH₂, or a bond; m is 0 or 1 ; n is 1-5; and p is 0-1 ; a pharmaceutically acceptable salt thereof, or an enantiomer thereof; or a conjugate thereof wherein the conjugate comprises a marker group; with the proviso that, in the compound of formula I, when R¹ is 4-t-butyl phenyl, 3,5-dimethylphenyl, 4-methoxyphenyl, 3-trifiuoromethylphenyl, 4-trifluoromethylphenyl or 4-bromophenyl, then R² is not furazan-4-yl, 4-methylfurazan-5-yl, furazan-4-yl-N-oxide, isoxazol-5-yl, 3-methylisoxazol-4-yl, pyrazin-2-yl, or 3-hydroxypyridin-2-yl. [0011] In some embodiments, the compound is of formula I, wherein R¹ is aryl, optionally substituted with one or more substituents selected from the group consisting of halo and alkyl.

[0012] In certain embodiments, the compound is of formula I, wherein A is NH. In certain embodiments, the compound is of formula I, wherein A is a bond. In certain embodiments, the compound is of formula I, wherein A is CH₂.

[0013] In certain embodiments, the compound is of formula I, wherein R¹ is phenyl, optionally substituted with one or more substituents selected from the group consisting of halo and alkyl.

[0014] In certain preferred embodiments, the compound is of formula I, wherein R¹ is phenyl, optionally substituted with one or more substituents selected from the group consisting of fluoro, methyl, and t-butyl.

[0015] In certain other preferred embodiments, the compound is of formula I, wherein R¹ is phenyl substituted with one or more substituents selected from the group consisting of fluoro, methyl, and t-butyl.

[0016] In certain embodiments, R² is selected from the group consisting of heterocyclyl, heteroaryl, cycloalkyl, dimethylamino alkyl, and benzyl, each of which is optionally substituted with one or more substituents selected from the group consisting of halo, hydroxy, carboxy, carboxy alkyl, dicarboxy alkyl, dicarboxy haloalkyl, alkoxy, alkylthio, acyl, acyloxy, thioacyl, acylthio, aryloxy, amino, aminoalkyl, alkylamino, dialkylamino, and trialkylamino.

[0017] In certain embodiments, R² is selected from the group consisting of heterocyclyl, heteroaryl, cycloalkyl, dimethylamino alkyl, and benzyl, each of which is optionally substituted with hydroxy.

[0018] In certain embodiments, R² is selected from the group consisting of pyrazinyl, dioxinyl, thiadiazolyl, oxazolinylmethyl, pyridinyl, phenyl, benzyl, piperidinyl, cyclopropyl, thiopheneyl, cyclohexyl, pyrazolyl, dimethylaminomethyl, N-protected piperidinyl, and oxadiazolyl, each of which is optionally substituted with hydroxy.

[0019] In some embodiments, the compound is of formula II, wherein

arylcarbonyl;

R , R , R , and R are independently hydrogen or alkyl, and p is 0-3.

[0020] In certain of the above embodiments, R is heteroaryl, optionally substituted with one or more substituents selected from alkyl, halo, cycloalkyl, aryl, fused aryl, fused cyclic, arylalkyl, and arylcarbonyl, wherein R¹¹, R¹², R¹³, and R¹⁴ are independently hydrogen or alkyl, and wherein R 18 is hydrogen or lower alkyl.

In certain preferred embodiments, R¹⁰ is

[0021] wherein R⁵ is selected from lower alkyl, aryl, arylalkyl, dialkylaminoalkyl, heterocyclyl, heteroaryl, and benzyl, each of which is optionally substituted with one or more substituents selected from alkyl, arylalkyl, heteroaryl alkyl, alkenyl, and arylalkyl, wherein each of said optional substituents are further optionally substituted with one or more substituents selected from halo, alkyl, monohalo alkoxy, dihalo alkoxy, trihalo alkoxy, hydroxy, carboxy, carboxy alkyl, dicarboxy alkyl, dicarboxy haloalkyl, sulfonyl, cyano, nitro, alkoxy, alkylthio, acyl, acyloxy, thioacyl, acylthio, aryloxy, amino, aminoalkyl, alkylamino, dialkylamino, trialkylamino, aminocarbonyl, aldehydo, and ureido.

[0022] In certain of the above embodiments, R³ and R⁴ are each independently ethyl or, taken together with the carbon atom to which they are attached, form a 5-membered ring.

[0023] In certain of the above embodiments, R⁵ is selected from the group consisting of thiophenopyrrolyl, phenyl, thiopheneyl, benzyl, dimethylamino alkyl, alkyl, benzodioxanyl, and cyclopenta[£>]thiopheneyl, each of which is optionally substituted with one or more substituents selected from the group consisting of halo, alkyl, phenylalkyl, dihalo alkoxy, and pyridyl alkyl.

[0024] In certain of the above embodiments, R⁵ is selected from the group consisting of thiophenopyrrolyl, phenyl, thiopheneyl, benzyl, dimethylamino alkyl, alkyl, benzodioxanyl, and cyclopenta[6]thiopheneyl, each of which is optionally substituted with one or more substituents selected from the group consisting of halo, alkyl, phenylalkyl, dihalo alkoxy, and pyridyl alkyl.

which is optionally substituted with one or more substituents selected from alkyl, aryl, arylalkyl, arylcarbonyl, and halo.

[0026] In some embodiments, the compound is of formula III, wherein

R⁶ and R⁷ are independently lower alkyl or, taken together with the carbon atom to which they are bonded, form a 5-7 membered cycloalkyl ring;

R is H or a substituent selected from halo, alkyl, monohalo alkyl, dihaloalkyl, trihaloalkyl, cyano, nitro, alkoxy, heterocyclyl, alkyl heterocyclyl, heterocyclylalkyl, alkylthio, aryloxy, amino, aminoalkyl, alkylamino, dialkylamino, trialkylamino.

R⁹ is H, OR¹⁵, or NR¹⁶R¹⁷; and n is 1-5.

[0027] In certain of the above embodiments, R⁶ and R⁷ are individually lower alkyl or, taken together with the carbon atom to which they are bonded, form a 5-7 membered cycloalkyl ring;

R⁸ is H or a substituent selected from the group consisting of halo, cyano, alkoxy, monohalo alkyl, dihaloalkyl, trihaloalkyl, morpholino alkyl, benzo, fused thiopheno, alkyl thiazolyl, phenyl, aryloxy, alkoxycarbonyl, amino, aminoalkyl, alkylamino, dialkylamino, and trialkylamino;

R⁹ is H, OR¹⁵, or NR^I6R¹⁷; and n is 1 or 2.

In certain of the above embodiments, R⁶ and R⁷ are individually lower alkyl or, taken together with the carbon atom to which they are bonded, form a 5-7 membered cycloalkyl ring; R is H or a substituent selected from the group consisting of halo, cyano, alkoxy, monohalo alkyl, dihaloalkyl, trihaloalkyl, morpholino alkyl, benzo, fused thiopheno, alkyl thiazolyl, phenyl, aryloxy, alkoxycarbonyl, amino, aminoalkyl, alkylamino, dialkylamino, and trialkylamino;

R⁹ is OR¹⁵; and n is 1 or 2.

In certain of the above embodiments, R⁶ and R⁷ are individually lower alkyl or, taken together with the carbon atom to which they are bonded, form a 5-7 membered cycloalkyl ring;

R⁹ is NR¹⁶R¹⁷; and n is 1 or 2.

[0028] Referring now to the terminology used genetically herein, the term "alkyl" means a straight-chain or branched alkyl substituent containing from, for example, 1 to about 6 carbon atoms, preferably from 1 to about 4 carbon atoms, more preferably from 1 to 2 carbon atoms. Examples of such substituents include methyl, ethyl, propyl, isopropyl, M-butyl, sec- butyl, isobutyl, tert-bvXy\, pentyl, isoamyl, hexyl, and the like.

[0029] The term "alkenyl" means a straight-chain or branched unsaturated alkyl substituent containing from, for example, 2 to about 8 carbon atoms, preferably from 2 to about 6 carbon atoms, more preferably from 2 to 4 carbon atoms. Examples of such substituents include ethenyl, propeneyl, buteneyl, pendenyl, hexeneyl, hepteneyl, octeneyl, and the like.

[0030] The term "cycloalkyl," as used herein, means a cyclic alkyl substituent containing from, for example, about 3 to about 8 carbon atoms, preferably from about 3 to about 7 carbon atoms, and more preferably from about 5 to about 6 carbon atoms. Examples of such substituents include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, and the like. The cyclic alkyl groups may be unsubstituted or further substituted with one or more alkyl groups such as methyl groups, ethyl groups, and the like. The term "fused cyclic" refers to two or more rings fused together so as to form a bicyclic or polycyclic group wherein at least two of the rings are attached to each other by way of adjaceet carbons on each ring. The term "fused cyclic" further includes bicyclic or polycyclic systems comprising one or more heteroatoms. Examples

heteroatom-containing fused cyclic systems include groups such

, and the like.

[0031] The term "heteroaryl," as used herein, refers to a 5, 6, or 7-membered aromatic ring system containing one or more heteroatoms selected from the group consisting of O, N, S, and combinations thereof. The heteroaryl group can be any suitable heteroaryl group. The heteroaryl group can be a monocyclic heteroaryl group or a bicyclic heteroaryl group.

Suitable bicyclic heteroaryl groups include monocylic heteroaryl rings fused to a C₆-Cio aryl ring. It is understood that a 6-membered heteroaryl group comprises 4n+2 π electrons, according to Huckel's Rule, and that a 5-, 7-, and 8-membered heteroaryl group has six electrons provided from a combination of p orbitals and an unshared pair of electrons provided by a heteroatom or heteroatoms which occupy bonding orbitals and constitute an aromatic sextet. Non-limiting examples of suitable heteroaryl groups include furanyl, thiopheneyl, pyrrolyl, pyrazolyl, imidazolyl, 1,2,3-triazolyl, 1,2,4-triazolyl, isoxazolyl, oxazolyl, isothiazolyl, thiazolyl, pyridinyl, pyrimidinyl, pyrazinyl, triazinyl, benzofuranyl, benzothiopheneyl, indolyl, quinolinyl, isoquinolinyl, benzimidazolyl, benzoxazolinyl, benzothiazolinyl, and quinazolinyl. The heteroaryl group can be linked at any open position of the heteroaryl group. For example, the furanyl group can be a furan-2-yl group or a furan-3-yl group, and the thiopheneyl group can be a thiophene-2-yl group or a

thiophene-3-yl group. The heteroaryl group is optionally substituted with 1 , 2, 3, 4, or 5 substituents as recited herein, wherein the optional substituent can be present at any open position on the heteroaryl group. The heteroaryl group is optionally a fused cyclic system as described herein.

[0032] The term "halo" or "halogen," as used herein, means a substituent selected from Group VIIA, such as, for example, fluorine, bromine, chlorine, and iodine. [0033] The term "aryl" refers to an unsubstituted or substituted aromatic carbocyclic substituent, as commonly understood in the art, and the term "C₆-Cio aryl" includes phenyl and naphthyl. It is understood that the term aryl applies to cyclic substituents that are planar and comprise 4n+2 π electrons, according to Huckel's Rule. The term "fused aryl" refers to an unsubstituted or substituted aromatic carbocyclic substituent having fused thereto a 5- or 6-membered ring.

[0034] The term "alkylaryl" refers to an unsubstituted or substituted alkyl group bonded to an an unsubstituted or substituted aryl group. The alkylaryl group is typically bonded to the core structure of the molecule by way of the alkyl portion of the alkylaryl group.

[0035] The term "arylalkyl" refers to an unsubstituted or substituted aryl group bonded to an an unsubstituted or substituted alkyl group. The arylalkyl group is typically bonded to the core structure of the molecule by way of the aryl portion of the arylalkyl group

[0036] The term "heterocycloalkyl," as used herein, means a non-aromatic cyclic alkyl substituent containing a heteroatom and further containing from, for example, about 3 to about 7 carbon atoms, preferably from about 3 to about 6 carbon atoms, and more preferably from about 3 to about 5 carbon atoms. The heterocycloalkyl group can be monocyclic or can be fused to another ring, wherein the other ring can be a cycloalkyl ring, an aryl ring, or another heterocycloalkyl ring. Examples of such substituents include tetrahydrofuranyl, tetrahydrothiopheneyl, pyrrolidinyl, piperidinyl, tetrahydroazepinyl, and the like. The heterocycloalkyl groups may be unsubstituted or further substituted with alkyl groups such as methyl groups, ethyl groups, and the like.

[0037] In certain embodiments of the compound of formula (I), R⁵ is selected from the group consisting of benzoxazol-2-yl, 5-bromo-benzoxazol-2-yl, 5-methyl-benzoxazol-2-yl, 6-methyl-benzoxazol-2-yl, 6-phenyl-benzoxazol-2-yl, benzoimidazol-2-yl, benzothiazol-2-yl, indol-l -yl, indol-2-yl, indol-3-yl, furan-2-yl, furan-3-yl, thiophene-2-yl, thiophene-3-yl, imidazol-l-yl, imidazol-4-yl, thiazol-2-yl, thiazol-4-yl, pyrazol-3-yl, pyrazol-4-yl, pyridin-2-yl, pyridin-3-yl, and pyridin-4-yl.

[0038] In preferred embodiments, R⁵ is selected from the group consisting of

benzoxazol-2-yl, 5-bromo-benzoxazol-2-yl, 5-methyl-benzoxazol-2-yl,

6-methyl-benzoxazol-2-yl, and 6-phenyl-benzoxazol-2-yl.

[0039] In a more preferred embodiment, R⁵ is benzoxazol-2-yl.

[0040] In any of the above embodiments, the compound or salt of formula (I), (II), or (III) can have at least one asymmetric carbon atom. When the compound or salt has at least one asymmetric carbon atom, the compound or salt can exist in the racemic form, in the form of its pure optical isomers, or in the form of a mixture wherein one isomer is enriched relative to the other. In particular, in accordance with the present invention, when the inventive compounds have a single asymmetric carbon atom, the inventive compounds may exist as racemates, i.e., as mixtures of equal amounts of optical isomers, i.e., equal amounts of two enantiomers, or in the form of a single enantiomer. As used herein, "single enantiomer" is intended to include a compound that comprises more than 50% of a single enantiomer (i.e., enantiomeric excess up to 100% pure enantiomer).

[0041] When the compound or salt has more than one chiral center, the compound or salt can therefore exist as a mixture of diastereomers or in the form of a single diastereomer. As used herein, "single diastereomer" is intended to mean a compound that comprises more than 50% of a single diastereomer (i.e., diastereomeric excess to 100% pure diastereomer).

[0042] The phrase "pharmaceutically acceptable salt" is intended to include nontoxic salts synthesized from the parent compound which contains a basic or acidic moiety by conventional chemical methods. Generally, such salts can be prepared by reacting the free acid or base forms of these compounds with a stoichiometric amount of the appropriate base or acid in water or in an organic solvent, or in a mixture of the two. Generally, nonaqueous media such as ether, ethyl acetate, ethanol, isopropanol, or acetonitrile are preferred. Lists of suitable salts are found in Remington 's Pharmaceutical Sciences, 18th ed., Mack Publishing Company, Easton, PA, 1990, p. 1445, and Journal of Pharmaceutical Science, 66, 2-19 (1977).

[0043] Suitable bases include inorganic bases such as alkali and alkaline earth metal bases, e.g., those containing metallic cations such as sodium, potassium, magnesium, calcium and the like. Non-limiting examples of suitable bases include sodium hydroxide, potassium hydroxide, sodium carbonate, and potassium carbonate. Suitable acids include inorganic acids such as hydrochloric acid, hydrobromic acid, hydroiodic acid, sulfuric acid, phosphoric acid, and the like, and organic acids such as p-toluenesulfonic, methanesulfonic acid, benzenesulfonic acid, oxalic acid, p-bromophenylsulfonic acid, carbonic acid, succinic acid, citric acid, benzoic acid, acetic acid, maleic acid, tartaric acid, fatty acids, long chain fatty acids, and the like. Preferred pharmaceutically acceptable salts of inventive compounds having an acidic moiety include sodium and potassium salts. Preferred pharmaceutically acceptable salts of inventive compounds having a basic moiety (e.g., a quinoline group or a dimethylaminoalkyl group) include hydrochloride and hydrobromide salts. The compounds of the present invention containing an acidic or basic moiety are useful in the form of the free base or acid or in the form of a pharmaceutically acceptable salt thereof.

[0044] It should be recognized that the particular counterion forming a part of any salt of this invention is usually not of a critical nature, so long as the salt as a whole is

pharmacologically acceptable and as long as the counterion does not contribute undesired qualities to the salt as a whole.

[0045] It is further understood that the above compounds and salts may form solvates, or exist in a substantially uncomplexed form, such as the anhydrous form. As used herein, the term "solvate" refers to a molecular complex wherein the solvent molecule, such as the crystallizing solvent, is incorporated into the crystal lattice. When the solvent incorporated in the solvate is water, the molecular complex is called a hydrate. Pharmaceutically acceptable solvates include hydrates, alcoholates such as methanolates and ethanolates, acetonitrilates and the like. These compounds can also exist in polymorphic forms.

[0046] The present invention is further directed to a pharmaceutical composition comprising a pharmaceutically acceptable carrier and at least one compound, salt, enantiomer, or conjugate described herein.

[0047] It is preferred that the pharmaceutically acceptable carrier be one that is chemically inert to the active compounds and one that has no detrimental side effects or toxicity under the conditions of use.

[0048] The choice of carrier will be determined in part by the particular compound of the present invention chosen, as well as by the particular method used to administer the composition. Accordingly, there is a wide variety of suitable formulations of the

pharmaceutical composition of the present invention. The following formulations for oral, aerosol, nasal, pulmonary, parenteral, subcutaneous, intravenous, intraarterial, intramuscular, intraperitoneal, intrathecal, intratumoral, topical, rectal, and vaginal administration are merely exemplary and are in no way limiting.

[0049] The pharmaceutical composition can be administered parenterally, e.g., intravenously, intraarterially, subcutaneously, intradermally, or intramuscularly. Thus, the invention provides compositions for parenteral administration that comprise a solution or suspension of the inventive compound or salt dissolved or suspended in an acceptable carrier suitable for parenteral administration, including aqueous and non-aqueous isotonic sterile injection solutions. [0050] Overall, the requirements for effective pharmaceutical carriers for parenteral compositions are well known to those of ordinary skill in the art. See, e.g., Banker and Chalmers, eds., Pharmaceutics and Pharmacy Practice, J. B. Lippincott Company,

Philadelphia, pp. 238-250 (1982), and Toissel, ASHP Handbook on Injectable Drugs, 4th ed., pp. 622-630 (1986). Such solutions can contain anti-oxidants, buffers, bacteriostats, and solutes that render the formulation isotonic with the blood of the intended recipient, and aqueous and non-aqueous sterile suspensions that can include suspending agents, solubilizers, thickening agents, stabilizers, and preservatives. The compound or salt of the present invention may be administered in a physiologically acceptable diluent in a pharmaceutical carrier, such as a sterile liquid or mixture of liquids, including water, saline, aqueous dextrose and related sugar solutions, an alcohol, such as ethanol, isopropanol, or hexadecyl alcohol, glycols, such as propylene glycol or polyethylene glycol, dimethylsulfoxide, glycerol ketals, such as 2,2-dimethyl-l,3-dioxolane-4-methanol, ethers, such as poly(ethyleneglycol) 400, an oil, a fatty acid, a fatty acid ester or glyceride, or an acetylated fatty acid glyceride with or without the addition of a pharmaceutically acceptable surfactant, such as a soap or a detergent, suspending agent, such as pectin, carbomers, methylcellulose,

hydroxypropylmethylcellulose, or carboxymethylcellulose, or emulsifying agents and other pharmaceutical adjuvants.

[0051] Oils useful in parenteral formulations include petroleum, animal, vegetable, or synthetic oils. Specific examples of oils useful in such formulations include peanut, soybean, sesame, cottonseed, corn, olive, petrolatum, and mineral. Suitable fatty acids for use in parenteral formulations include oleic acid, stearic acid, and isostearic acid. Ethyl oleate and isopropyl myristate are examples of suitable fatty acid esters.

[0052] Suitable soaps for use in parenteral formulations include fatty alkali metal, ammonium, and triethanolamine salts, and suitable detergents include (a) cationic detergents such as, for example, dimethyl dialkyl ammonium halides, and alkyl pyridinium halides, (b) anionic detergents such as, for example, alkyl, aryl, and olefin sulfonates, alkyl, olefin, ether, and monoglyceride sulfates, and sulfosuccinates, (c) nonionic detergents such as, for example, fatty amine oxides, fatty acid alkanolamides, and polyoxyethylenepolypropylene copolymers, (d) amphoteric detergents such as, for example, alkyl-beta-aminopropionates, and 2-alkyl-imidazoline quaternary ammonium salts, and (e) mixtures thereof.

[0053] The parenteral formulations can contain preservatives and buffers. In order to minimize or eliminate irritation at the site of injection, such compositions may contain one or more nonionic surfactants having a hydrophile-lipophile balance (HLB) of from about 12 to about 17. The quantity of surfactant in such formulations will typically range from about 5 to about 15% by weight. Suitable surfactants include polyethylene sorbitan fatty acid esters, such as sorbitan monooleate and the high molecular weight adducts of ethylene oxide with a hydrophobic base, formed by the condensation of propylene oxide with propylene glycol. The parenteral formulations can be presented in unit-dose or multi-dose sealed containers, such as ampules and vials, and can be stored in a freeze-dried (lyophilized) condition requiring only the addition of the sterile liquid excipient, for example, water, for injections, immediately prior to use. Extemporaneous injection solutions and suspensions can be prepared from sterile powders, granules, and tablets of the kind previously described.

[0054] Topical formulations, including those that are useful for transdermal drug release, are well-known to those of skill in the art and are suitable in the context of the invention for application to skin. Topically applied compositions are generally in the form of liquids, creams, pastes, lotions and gels. Topical administration includes application to the oral mucosa, which includes the oral cavity, oral epithelium, palate, gingival, and the nasal mucosa. In some embodiments, the composition contains at least one active component and a suitable vehicle or carrier. It may also contain other components, such as an anti-irritant. The carrier can be a liquid, solid or semi-solid. In embodiments, the composition is an aqueous solution. Alternatively, the composition can be a dispersion, emulsion, gel, lotion or cream vehicle for the various components. In one embodiment, the primary vehicle is water or a biocompatible solvent that is substantially neutral or that has been rendered substantially neutral. The liquid vehicle can include other materials, such as buffers, alcohols, glycerin, and mineral oils with various emulsifiers or dispersing agents as known in the art to obtain the desired pH, consistency and viscosity. It is possible that the compositions can be produced as solids, such as powders or granules. The solids can be applied directly or dissolved in water or a biocompatible solvent prior to use to form a solution that is substantially neutral or that has been rendered substantially neutral and that can then be applied to the target site. In embodiments of the invention, the vehicle for topical application to the skin can include water, buffered solutions, various alcohols, glycols such as glycerin, lipid materials such as fatty acids, mineral oils, phosphoglycerides, collagen, gelatin and silicone based materials.

[0055] Formulations suitable for oral administration can consist of (a) liquid solutions, such as a therapeutically effective amount of the inventive compound dissolved in diluents, such as water, saline, or orange juice, (b) capsules, sachets, tablets, lozenges, and troches, each containing a predetermined amount of the active ingredient, as solids or granules, (c) powders, (d) suspensions in an appropriate liquid, and (e) suitable emulsions. Liquid formulations may include diluents, such as water and alcohols, for example, ethanol, benzyl alcohol, and the polyethylene alcohols, either with or without the addition of a

pharmaceutically acceptable surfactant, suspending agent, or emulsifying agent. Capsule forms can be of the ordinary hard- or soft-shelled gelatin type containing, for example, surfactants, lubricants, and inert fillers, such as lactose, sucrose, calcium phosphate, and corn starch. Tablet forms can include one or more of lactose, sucrose, mannitol, corn starch, potato starch, alginic acid, microcrystalline cellulose, acacia, gelatin, guar gum, colloidal silicon dioxide, croscarmellose sodium, talc, magnesium stearate, calcium stearate, zinc stearate, stearic acid, and other excipients, colorants, diluents, buffering agents, disintegrating agents, moistening agents, preservatives, flavoring agents, and pharmacologically compatible excipients. Lozenge forms can comprise the active ingredient in a flavor, usually sucrose and acacia or tragacanth, as well as pastilles comprising the active ingredient in an inert base, such as gelatin and glycerin, or sucrose and acacia, emulsions, gels, and the like containing, in addition to the active ingredient, such excipients as are known in the art.

[0056] The compound or salt of the present invention, alone or in combination with other suitable components, can be made into aerosol formulations to be administered via inhalation. The compounds are preferably supplied in finely divided form along with a surfactant and propellant. Typical percentages of active compound are 0.01%-20% by weight, preferably 1 %- 10%. The surfactant must, of course, be nontoxic, and preferably soluble in the propellant. Representative of such surfactants are the esters or partial esters of fatty acids containing from 6 to 22 carbon atoms, such as caproic, octanoic, lauric, palmitic, stearic, linoleic, linolenic, olesteric and oleic acids with an aliphatic polyhydric alcohol or its cyclic anhydride. Mixed esters, such as mixed or natural glycerides may be employed. The surfactant may constitute 0.1 %-20% by weight of the composition, preferably 0.25%-5%. The balance of the composition is ordinarily propellant. A carrier can also be included as desired, e.g., lecithin for intranasal delivery. These aerosol formulations can be placed into acceptable pressurized propellants, such as dichlorodifluoromethane, propane, nitrogen, and the like. They also may be formulated as pharmaceuticals for non-pressured preparations, such as in a nebulizer or an atomizer. Such spray formulations may be used to spray mucosa. [0057] Additionally, the compound or salt of the present invention may be made into suppositories by mixing with a variety of bases, such as emulsifying bases or water-soluble bases. Formulations suitable for vaginal administration may be presented as pessaries, tampons, creams, gels, pastes, foams, or spray formulas containing, in addition to the active ingredient, such carriers as are known in the art to be appropriate.

[0058] It will be appreciated by one of ordinary skill in the art that, in addition to the aforedescribed pharmaceutical compositions, the compound or salt of the present invention may be formulated as inclusion complexes, such as cyclodextrin inclusion complexes, or liposomes. Liposomes serve to target the compounds to a particular tissue, such as lymphoid tissue or cancerous hepatic cells. Liposomes can also be used to increase the half-life of the inventive compound. Liposomes useful in the present invention include emulsions, foams, micelles, insoluble monolayers, liquid crystals, phospholipid dispersions, lamellar layers and the like. In these preparations, the active agent to be delivered is incorporated as part of a liposome, alone or in conjunction with a suitable chemotherapeutic agent. Thus, liposomes filled with a desired inventive compound or salt thereof, can be directed to the site of a specific tissue type, hepatic cells, for example, where the liposomes then deliver the selected compositions. Liposomes for use in the invention are formed from standard vesicle-forming lipids, which generally include neutral and negatively charged phospholipids and a sterol, such as cholesterol. The selection of lipids is generally guided by consideration of, for example, liposome size and stability of the liposomes in the blood stream. A variety of methods are available for preparing liposomes, as described in, for example, Szoka et al., Ann. Rev. Biophys. Bioeng., 9, 467 (1980), and U.S. Patents 4,235,871, 4,501,728, 4,837,028, and 5,019,369. For targeting to the cells of a particular tissue type, a ligand to be

incorporated into the liposome can include, for example, antibodies or fragments thereof specific for cell surface determinants of the targeted tissue type. A liposome suspension containing a compound or salt of the present invention may be administered intravenously, locally, topically, etc. in a dose that varies according to the mode of administration, the agent being delivered, and the stage of disease being treated.

[0059] The invention further provides a method for treating or preventing a disease or disorder responsive to reduction of lipid storage droplets in an animal in need thereof comprising administering an effective amount of a compound of formula I, II, or III or a combination thereof:

I II III

wherein:

R^! is selected from alkyl, aryl, arylalkyl, and alkylaryl, each of which is optionally substituted with one or more substituents selected from halo, alkyl, hydroxy, carboxy, phosphoryl, phosphonyl, phosphono alkyl, carboxy alkyl, dicarboxy alkyl, dicarboxy haloalkyl, sulfonyl, cyano, nitro, alkoxy, alkylthio, acyl, acyloxy, thioacyl, acylthio, aryloxy, amino, aminoalkyl, alkylamino, dialkylamino, trialkylamino, guanidino, aminocarbonyl, aldehydo, and ureido;

aminocarbonyl, aldehydo, and ureido;

arylcarbonyl;

R^{1 1} , R¹², R¹³, and R¹⁴ are independently hydrogen or alkyl;

R⁶ and R⁷ are independently hydrogen,lower alkyl, or aryl alkyl oxyalkyl, or, taken together with the carbon atom to which they are bonded, form a 5-7 membered ring;

18

R is hydrogen or lower alkyl;

R¹⁹ is hydrogen or halo;

A is NH(CH₂)_m, CH₂, or a bond; m is 0 or 1 ; n is 1 -5; and p is 0-1 ; a pharmaceutically acceptable salt thereof, or an enantiomer thereof; or a conjugate thereof wherein the conjugate comprises a marker group.

[0060] The disease or disorder can be any suitable disease or disorder and can be, for example, selected from the group consisting of Gaucher disease, Fabry disease, Farber's disease, GM1 gangliosidoses, Tay-Sachs disease, Sandhoff disease, Krabbe disease, metachromatic leukodystrophy, obesity, atherosclerosis, and ectopic fat deposition.

[0061] Gaucher's disease is a genetic disease in which a fatty substance (lipid) accumulates in cells and certain organs. Gaucher's disease is the most common of the lysosomal storage diseases. It is caused by a hereditary deficiency of the enzyme

glucocerebrosidase (also known as acid β-glucosidase). The enzyme acts on a fatty substance glucocerebroside (also known as glucosylceramide). When the enzyme is defective, glucocerebroside accumulates, particularly in white blood cells (mononuclear leukocytes). Glucocerebroside can collect in the spleen, liver, kidneys, lungs, brain and bone marrow.

[0062] Symptoms may include enlarged spleen and liver, liver malfunction, skeletal disorders and bone lesions that may be painful, severe neurologic complications, swelling of lymph nodes and (occasionally) adjacent joints, distended abdomen, a brownish tint to the skin, anemia, low blood platelets and yellow fatty deposits on the white of the eye (sclera). Persons affected most seriously may also be more susceptible to infection. Some forms of Gaucher's disease may be treated with enzyme replacement therapy.

[0063] Fabry disease (also known as Fabry's disease, Anderson-Fabry disease, angiokeratoma corporis diffusum and alpha-galactosidase A deficiency) is a rare X-linked recessive (inherited) lysosomal storage disease, which can cause a wide range of systemic symptoms. Fabry disease results from a deficiency of the enzyme alpha galactosidase A (a- GAL A, encoded by GLA) due to mutation which causes a glycolipid known as

globotriaosylceramide (abbreviated as Gb3, GL-3, or ceramide trihexoside) to accumulate within the blood vessels, other tissues, and organs. This accumulation leads to an impairment of their proper function.

[0064] Farber disease (also known as Farber's lipogranulomatosis, ceramidase deficiency, "Fibrocytic dysmucopolysaccharidosis," and "Lipogranulomatosis" is a rare autosomal recessive lysosomal storage disease that cause an accumulation of fatty material lipids leading to abnormalities in the joints, liver, throat, tissues and central nervous system.

Normally, the enzyme ceramidase breaks down fatty material in the body's cells. In Farber Disease, the gene responsible for making this enzyme is mutated. Hence, the fatty material is never broken down and, instead, accumulates in various parts of the body, leading to the signs and symptoms of the disorder.

[0065] The GM1 gangliosidoses are caused by a deficiency of beta- galactosidase, with resulting abnormal storage of acidic lipid materials in cells of the central and peripheral nervous systems, but particularly in the nerve cells.

[0066] Tay-Sachs disease is caused by insufficient activity of an enzyme called hexosaminidase A that catalyzes the biodegradation of fatty acid derivatives known as gangliosides. Hexosaminidase A is a vital hydrolytic enzyme, found in the lysosomes, that breaks down phospholipids. When Hexosaminidase A no longer functions properly, the lipids accumulate in the brain and interfere with normal biological processes. Gangliosides are made and biodegraded rapidly in early life as the brain develops. Patients and carriers of Tay-Sachs disease can be identified by a simple blood test that measures hexosaminidase A activity.

[0067] Sandhoff disease, also known as Sandhoff-Jatzkewitz disease, variant 0 of GM2- Gangliosidosis or Hexosaminidase A and B deficiency, is a lysosomal genetic, lipid storage disorder caused by the inherited deficiency to create functional beta-hexosaminidases A and B. These catabolic enzymes are needed to degrade the neuronal membrane components, ganglioside GM2, its derivative GA2, the glycolipid globoside in visceral tissues, and some oligosaccharides. Acccumulation of these metabolites leads to a progressive destruction of the central nervous system and eventually to death. The rare autosomal recessive

neurodegenerative disorder is clinically almost indistinguishable from Tay-Sachs disease, another genetic disorder that disrupts beta-hexosaminidases A and S.

[0068] Krabbe disease is caused by mutations in the GALC gene located on chromosome 14 (14q31), which causes a deficiency of an enzyme called galactocerebrosidase. The build up of unmetabolized lipids affects the growth of the nerve's protective myelin sheath (the covering that insulates many nerves) and causes severe degeneration of motor skills. As part of a group of disorders known as leukodystrophies, Krabbe disease results from the imperfect growth and development of myelin

[0069] Metachromatic leukodystrophy (MLD, also called Arylsulfatase A deficiency) is a lysosomal storage disease which is commonly listed in the family of leukodystrophies.

Leukodystrophies affect the growth and/or development of myelin, the fatty covering which acts as an insulator around nerve fibers throughout the central and peripheral nervous systems.

[0070] Obesity, atherosclerosis, and ectopic fat deposition all relate to the accumulation of fat within mammals. Obesity is characterized by the excessive presence of tissues containing lipids, which are contained within lipid droplets within the cells. Atherosclerosis is at least partially characterized by the presence of fibro-lipid plaques, wherein the accumulation of lipid-laden cells underneath the intima of the arteries results in the formation of such plaques. Ectopic fat deposition results from deposition of fat in internal organs, arteries, and muscle. Thus, reduction of lipid storage droplets within cells is expected to mitigate and/or ameliorate the detrimental effects of fat deposition within mammals.

[0071] The term "animal" includes mammal. The term "mammal" includes, but is not limited to, the order Rodentia, such as mice, and the order Logomorpha, such as rabbits. It is preferred that the mammals are from the order Carnivora, including Felines (cats) and Canines (dogs). It is more preferred that the mammals are from the order Artiodactyla, including Bovines (cows) and Swines (pigs) or of the order Perssodactyla, including Equines (horses). It is most preferred that the mammals are of the order Primates, Ceboids, or Simioids (monkeys) or of the order Anthropoids (humans and apes). An especially preferred mammal is the human. Furthermore, the subject can be the unborn offspring of any of the forgoing hosts, especially mammals (e.g., humans), in which case any screening of the subject or cells of the subject, or administration of compounds to the subject or cells of the subject, can be performed in utero.

[0072] "Treating" within the context of the present invention, means an alleviation of symptoms associated with a disorder or disease, or halt of further progression or worsening of those symptoms. For example, within the context of treating patients with a disease or disorder responsive to reduction of lipid storage droplets, successful treatment may be used in conjunction with dietary restrictions aimed at reducing lipids in the diet. Within the context of treating patients with a disease or disorder responsive to reduction of lipid storage droplets, successful treatment may include a reduction in clinical markers such as levels of lipids in blood or urine, and/or changes in clinical symptoms. Treatment may also include

administering the pharmaceutical formulations of the present invention in combination with other therapies. For example, the compounds and pharmaceutical formulations of the present invention may be administered on a chronic basis. The compounds of the invention can also be administered in conjunction with dietary restrictions.

[0073] "Preventing" within the context of the present invention, refers to a prophylactic treatment of an animal - an individual prone or subject to development of a condition, in particular, a disease or disorder responsive to reduction of lipid storage droplets. For example, those of skill in the medical arts may be able to determine, based on clinical symptoms and patient history, a statistical predisposition of a particular individual to the development of the aforesaid disease or disorder. For example, a family history of a disease or disorder responsive to reduction of lipid storage droplets can be used to assess the predisposition of a particular individual to the development of such disorders and thus inform the individual as to the desirability of preventative treatment with a compound or salt of the invention or a medicament formed therefrom. Accordingly, an individual predisposed to the development of a disease or disorder responsive to reduction of lipid storage droplets may be treated with a compound or a composition of the present invention in order to prevent, inhibit, reduce the effect of a development of, or slow the development of the disease or disorder or ameliorate the condition.

[0074] One skilled in the art will appreciate that suitable methods of utilizing a compound and administering it to a human for the treatment or prevention of disease states, in particular, those responsive to reduction of lipid storage droplets, e.g., Gaucher disease, Fabry disease, Farber's disease, GM1 gangliosidoses, Tay-Sachs disease, Sandhoff disease, Krabbe disease, metachromatic leukodystrophy, obesity, atherosclerosis, and ectopic fat deposition, which would be useful in the method of the present invention, are available. Although more than one route can be used to administer a particular compound, a particular route can provide a more immediate and more effective reaction than another route.

Accordingly, the described methods are merely exemplary and are in no way limiting.

[0075] The dose administered to a mammal, particularly, a human, in accordance with the present invention should be sufficient to effect the desired response. Such responses include reversal or prevention of the adverse effects of the disease for which treatment is desired or to elicit the desired benefit. One skilled in the art will recognize that dosage will depend upon a variety of factors, including the age, condition, and body weight of the human, as well as the source, particular type of the disease, and extent of the disease in the human. The size of the dose will also be determined by the route, timing and frequency of administration as well as the existence, nature, and extent of any adverse side-effects that might accompany the administration of a particular compound and the desired physiological effect. It will be appreciated by one of skill in the art that various conditions or disease states may require prolonged treatment involving multiple administrations.

[0076] Suitable doses and dosage regimens can be determined by conventional range- finding techniques known to those of ordinary skill in the art. Generally, treatment is initiated with smaller dosages that are less than the optimum dose of the compound.

Thereafter, the dosage is increased by small increments until the optimum effect under the circumstances is reached. The present inventive method typically will involve the administration of about 0.1 to about 300 mg of one or more of the compounds described above per kg body weight of the mammal.

[0077] By way of example and not intending to limit the invention, the dose of the pharmaceutically active agent(s) described herein for methods of preventing diseases or disorders responsive to reduction can be about 0.001 to about 1 mg/kg body weight of the subject being treated per day, for example, about 0.001 mg, 0.002 mg, 0.005 mg, 0.010 mg, 0.015 mg, 0.020 mg, 0.025 mg, 0.050 mg, 0.075 mg, 0.1 mg, 0.15 mg, 0.2 mg, 0.25 mg, 0.5 mg, 0.75 mg, or 1 mg/kg body weight per day. The dose of the pharmaceutically active agent(s) described herein for methods of treating diseases or disorders, e.g., diseases responsive to reduction of lipid storage droplets, can be about 1 to about 1000 mg/kg body weight of the subject being treated per day, for example, about 1 mg, 2 mg, 5 mg, 10 mg, 15 mg, 0.020 mg, 25 mg, 50 mg, 75 mg, 100 mg, 150 mg, 200 mg, 250 mg, 500 mg, 750 mg, or 1000 mg/kg body weight per day. [0078] In certain embodiments, the invention provides a method of identifying a molecular target involved in lipid storage in a cell, comprising contacting the cell with a compound of formula I, II, or III as described herein to form a complex of the target and the compound, pharmaceutically acceptable salt thereof, or an enantiomer thereof; and detecting the presence of complex of the target and the compound in the cell, wherein the presence of the complex indicates the presence of the molecular target in the cell. The compound can be a compound as described herein or can be a conjugate thereof wherein the conjugate comprises a marker group. Suitable conjugates can be, for example, conjugates wherein the compound further comprises a biotinylated moiety, a fluorescent moiety (e.g., a dye moiety), and the like. The conjugates can be formed for example by attaching a biotinylated moiety or a fluorescent moiety to the compound using any suitable chemistry.

[0079] Detection of the complex and the compound in the cell can be accomplished using any suitable means. Non-limiting means to detection of the complex and the compound in the cell include determining a change in a spectral property such as adsorption of UV light, by use of affinity chromatography wherein a biotinylated moiety interacts with a suitable component of a chromatography column, and the like.

[0080] In certain embodiments, the method further comprises isolating the complex. For example, use of affinity chromatography in conjunction with a biotinylated derivative of the compound can allow for isolation of the complex.

[0081] In certain embodiments, the invention provides a method of identifying a molecular target involved in lipid storage in a cell, comprising contacting the cell with a compound of formula I, II, or III, determining a change in an activity of the molecular target, wherein the change in the activity of the molecular target indicates the activity of the molecular target in lipid storage in the cell. The activity of the molecular target can be determined while the molecular target is present in the cell, for example, by determining a change in the production one or more downstream products resulting from activity of the molecular target. In other embodiments, the molecular target can be isolated from other components of the cell and the change of its activity can be determined via assay of the isolated molecular target.

[0082] The compounds of the invention can be synthesized by any suitable method, for example, via the methods depicted in Schemes I-III set forth in Examples 3-5.

[0083] The following examples further illustrate the invention but, of course, should not be construed as in any way limiting its scope. [0084] General Methods for Chemistry. All air or moisture sensitive reactions were performed under positive pressure of nitrogen with oven-dried glassware. Anhydrous solvents such as dichloromethane, NN-dimethylformamide (DMF), acetonitrile, methanol and triethylamine were obtained by purchasing from Sigma-Aldrich. Preparative purification was performed on a Waters semi-preparative HPLC. The column used was a Phenomenex Luna CI 8 (5 micron, 30 x 75 mm) at a flow rate of 45 mL/min. The mobile phase consisted of acetonitrile and water (each containing 0.1 % trifluoroacetic acid). A gradient of 10% to 50% acetonitrile over 8 minutes was used during the purification. Fraction collection was triggered by UV detection (220 nM). Analytical analysis was performed on an Agilent LC/MS (Agilent Technologies, Santa Clara, CA). Method 1 : A 7 minute gradient of 4% to 100% Acetonitrile (containing 0.025% trifluoroacetic acid) in water (containing 0.05% trifluoroacetic acid) was used with an 8 minute run time at a flow rate of 1 mL/min. A Phenomenex Luna CI 8 column (3 micron, 3 x 75 mm) was used at a temperature of 50°C. Method 2: A 3 minute gradient of 4% to 100% Acetonitrile (containing 0.025%

trifluoroacetic acid) in water (containing 0.05% trifluoroacetic acid) was used with a 4.5 minute run time at a flow rate of 1 mL/min. A Phenomenex Gemini Phenyl column (3 micron, 3 x 100 mm) was used at a temperature of 50° C. Purity determination was performed using an Agilent Diode Array Detector on both Method 1 and Method 2. Mass determination was performed using an Agilent 6130 mass spectrometer with electrospray ionization in the positive mode. 1H NMR spectra were recorded on Varian 400 MHz spectrometers. Chemical Shifts are reported in ppm with tetramethylsilane (TMS) as internal standard (0 ppm) for CDC1₃ solutions or undeuterated solvent (DMSO-H6 at 2.49 ppm) for DMSO-d6 solutions. All of the analogs for assay have purity greater than 95% based on both analytical methods. High resolution mass spectrometry was recorded on an Agilent 6210 Time-of-Flight LC/MS system. Confirmation of molecular formula was accomplished using electrospray ionization in the positive mode with the Agilent Masshunter software (version B.02).

EXAMPLE 1

[0085] This example demonstrates a primary qHTS assay for lipid storage modulators. Almost all mammalian components were identified and characterized in the fruit fly

Drosophila melanogaster (Bohni, R. et al., Cell 1999, 97, 865-75; Gronke, S. et al. Curr Biol 2003, 13, 603-6; Gronke, S. et al., Cell Metab 2005, 1 , 323-30; Gronke, S. et al. PLoS Biol 2007, 5, el 37; Teixeira, L. et al. Mech Dev 2003, 120, 1071-81). Additionally, LDs of Drosophila and mammals are coated with a similar set of proteins (Bartz, R. et al., J

Proteome Res 2007, 6, 3256-65; Beller, M. et al. Mol Cell Proteomics 2006, 5, 1082-94; Cermelli, S. et al. Curr Biol 2006, 16, 1783-95; Liu, P. et al, J Biol Chem 2004, 279, 3787- 92). Therefore, Drosophila is a prime model organism for lipid storage focused research due to the evolutionary conservation of key components, as well as certain advantages, including minimized redundancy of pathway components.

It has been shown that Drosophila melanogaster encodes for orthologs of >60% of the human disease-associated genes, making it a prime in vivo system to study disease pathways (Chien, S. et al. Nucleic Acids Res.lQQl, 30, 149-151).

[0086] The qHTS was performed with embryonic Drosophila S3 cells (Bloomington Drosophila Stock Center [DGRC]), that showed excellent oleic acid feeding characteristics and good performance during automated liquid handling in 1 ,536-well format (Table 2). 4 μΐ of cells at 1.25 x 10⁶ cells/ml were dispensed into LoBase Aurora COC 1,536-well plates (black walled, clear bottom) with a bottle-valve solenoid-based dispenser (Kalypsys) to obtain 5,000 cells/well. A total of 23 nl of compound solution of different concentrations was transferred to the assay plates using a Kalypsys pin tool equipped with a 1,536-pin array containing 10-nl slotted pins (FP1 S10, 0.457-mm diameter, 50.8 mm long; V&P Scientific). One microliter of oleic acid (400 μΜ) was added, and the plate was lidded with stainless steel rubber gasket-lined lids containing pinholes. After 18-24 h incubation at 24 °C and 95% humidity, 4 μΐ of BOD IP Y 493/503 (Molecular Probes) was added to the wells to stain lipid droplets, and the Cell Tracker Red CMTPX dye (Molecular Probes) was added to enumerate cell number. Fluorescence was detected by excitation of the fluorophores with a 488 nm laser on an Acumen Explorer (TTP Lab Tech). The total intensity in channel 1 (500-530 nm) reflected lipid droplet accumulation. Cells were detected using channel 3 (575-640 nm) with 5 μιη width and 100 μηι depth filters. The ratio of the total intensity in PMT channel 1 over total intensity of channel 3 was also calculated. Percent activity was computed relative to an internal control (100% inhibited lipid droplet deposition due to the presence of 20 μΜ

Triacsin C), which was added to 32 wells/plate.

EXAMPLE 2

[0087] This example demonstrates a cytotoxicity assay for lipid storage modulators. [0088] Cytotoxicity was tested using CellTiter-Glo to measure ATP levels using a final compound concentration of 46.2 μΜ to 0.3 nM and a 24 hr time point with the following protocol: Cytotoxicity test after compound treatment was measured using a luciferase- coupled ATP quantitation assay (CellTiter-Glo, Promega) for lipid storage modulators in Drosophila S3 Cells. The change of intracellular ATP content indicates the number of metabolically competent cells after compound treatment. S3cells were harvested from T225 flask and resuspended in Schneider's Drosophila medium with 5% FCS and. Then 4μ1 of 1.25 x 106 cells/ml resuspended cells was dispensed into each well of white, solid bottom, 1536- well tissue culture-treated plates using a Multidrop Combi dispenser. A total of 23 nl of compound solution of different concentrations or positive control (20mM stock of

Tetraoctylammonium bromide) in DMSO was transferred to each well of the assay plate using a pintool (Kalypsys, San Diego, CA), One microliter of oleic acid (400 μΜ) was added, and the plate was lidded with stainless steel rubber gasket-lined lids containing pinholes. After 24 hours incubation at 24 °C and 95% humidity, 4μ1 of CellTilter-GloTM luminescent substrate mix (Promega) was added to each well. The plate was incubated at room

temperature for 30 minutes. The plates were measured on a ViewLux plate reader

(PerkinElmer) with clear filter. The final compounds concentration of 46.2μΜ to 0.3nM.

EXAMPLE 3

[0089] This example demonstrates a synthesis of an exemplary embodiment of a compound of Formula I of the invention.

[0090] The synthesis is depicted in Scheme I.

Scheme 1

ML206

[0091] Scheme 1 , Steps 1 -3 were perfomed according to the procedure described in Guo, S. et aL, J. Med. Chem. 2010, 53, 649-659 [0092] Scheme 1 , Step 4. l-(2,4-difluorophenyl)-4,5,6,7-tetrahydro-l H-indazol-4-amine (0.1 g, 0.401 mmol) and picolinic acid (0.049 g, 0.401 mmol) were dissolved in DMF (2 ml) and DIPEA (0.091 ml, 0.522 mmol) was added, followed by HATU (0.183 g, 0.481 mmol); the reaction was stirred at RT for 2 hrs, then purified by directly injecting to a Waters© reverse phase purification system.

[0093] Scheme 1, Step 5. Chiral chromotography was performed on a Chiralpac IB column (2 cm x 25 cm, 20 micron) using EtOH/Hexane (60/40, v/v) as the eluent at a flow rate of 4.0 mL/min, with a 30 min run time to give enantiomerically pure ML206.

[0094] Ή NMR (400 MHz, DMSO-cfe); 8.60 (m. 2H), 8.08 (m. 1H), 8.00 (m, 1H), 7.51- 7.73 (m, 3H), 7.25 (m, 1H), 5.14 (m, 1H), 2.38-2.56 (m, 2H), 1.70-2.01 (m, 4H). Method 1 , retention time, 5.336 min; Method 2, retention time 3.267 min; HRMS: m/z (M ) =

354.1298 (Calculated for Ci₉Hi₆F₂N₄0 = 354.1292). [a]_D +82 (c=0.22, MeOH). Solubility (PBS, pH 7.4, 23 °C) = 20.4 gJmL.

EXAMPLE 4

[0095] This example demonstrates a synthesis of an exemplary embodiment of a compound of Formula II of the invention.

[0096] The synthesis is depicted in Scheme II.

Scheme 2

[0097] Scheme 2, Step 1. HATU (0.751 g, 1.974 mmol) and DIPEA (0.94 ml, 5.38 mmol) were added to a solution of 4H-thieno[3,2-b]pyrrole-5-carboxylic acid (0.3 g, 1.794 mmol) in DMF (25 ml). The solution was stirred at room temperature for 30 min, and then 2- (3,4-diethoxyphenyl)ethanamine (0.413 g, 1.974 mmol) was added. The reaction was stirred at room temperature overnight. Water (40 ml) was added to the mixture. The solid was filtered and washed with water, and dried. The crude product was used in the next reaction without further purification.

[0098] Scheme 2, Step 2. Sodium hydride (3.68 mg of 60 wt% dispersion in mineral oil, 0.092 mmol) was added to the solution of N-(3,4-diethoxyphenethyl)-4H-thieno[3,2- b]pyrrole-5-carboxamide (30 mg, 0.084 mmol) in DMF (1.5 ml). The mixture was stirred at room temperature for 15 min. l-(bromomethyl)-3-methylbenzene (0.014 ml, 0.1 mmol) was added to this mixture. The reaction mixture was stirred at room temperature overnight. The DMF solution was purified by directly injecting to a Waters™ reverse phase purification system to give the title product as a TFA salt.

[0099] Ή NMR (400 MHz, DMSO- ₆)™ ppm 8.29 (t, J=5.67 Hz, 1 H), 7.39 (d, J=5.48 Hz, 1 H), 7.08 - 7.15 (m, 2 H), 7.04 (s, 1 H), 6.96 - 7.02 (m, 2 H), 6.87 (d, J-7.43 Hz, 1 H), 6.75 - 6.83 (m, 2 H), 6.66 (dd, J=8.22, 1.96 Hz, 1 H), 5.71 (s, 2 H), 3.93 (qd, J=6.98, 4.70 Hz, 4 H), 3.34 - 3.43 (m, 2 H), 2.70 (t, J=7.24 Hz, 2 H), 2.19 (s, 3 H), 1.25 (dt, J=10.27, 6.90 Hz, 6 H). Method 1 , retention time, 6.81 1 min; Method 2, retention time 3.787 min; HRMS: m/z (M+H⁺) = 462.1985 (Calculated for C₂₇H₃oN₂0₃S = 462.1977). Solubility (PBS, pH 7.4, 23 °C) = 5.9 μg/mL.

EXAMPLE 5

[00100] This example demonstrates a synthesis of an exemplary embodiment of a compound of Formula III of the invention.

[00101] The synthesis is depicted in Scheme 3.

Scheme 3

2. HATU / DIPEA/ DMF

[00102] Scheme 3, Step 1. A solution of NaOH (0.028 g, 0.698 mmol) in Water (1 ml) was added to a suspension of 1 -aminocyclohexanecarboxylic acid (0.1 g, 0.698 mmol) in 1 ,4- dioxane (3 ml) at RT. The mixture was stirred at RT for 20 min (clear solution). A solution of 2,4-dichloro- l -isocyanatobenzene (0.131 g, 0.698 mmol) in dioxane (2 ml) was added dropwise to the reaction mixture at RT. The resulting solution was stirred at RT for 1 hr, and then evaporated to dryness under reduced pressure to give the title compound.

[00103] Scheme 3, Step 2. HATU (81 mg, 0.214 mmol), then DIPEA (0.102 ml, 0.584 mmol) were added to a solution of 2-(3-(2-chlorophenyl)ureido)-2-methylpropanoic acid (50 mg, 0.195 mmol) in DMF (1.5 ml). The solution was stirred at RT for 30 min, and then ethyl piperidine-4-carboxylate (0.033 ml, 0.214 mmol) was added. The reaction was stirred at RT for 3 hrs. The DMF solution was purified by directly injecting to a Waters® reverse phase purification system to give ML220 as a TFA salt.

[0100] Ή NMR (400 MHz, DMSO- ₆)™ ppm 8.03 (dd, J=8.41 , 1.56 Hz, 1 H), 7.94 (s, 1 H), 7.42 (s, 1 H), 7.35 (dd, J=8.02, 1.37 Hz, 1 H), 7.18 (ddd, J=8.41, 7.24, 1.57 Hz, 1 H), 6.85 - 6.96 (m, 1 H), 4.28 (dt, J=13.16, 3.30 Hz, 2 H), 3.96 (q, J=7.17 Hz, 2 H), 2.76 - 2.99 (m, 2 H), 2.43 - 2.55 (m, 1 H), 1.73 (dd, J=13.11, 2.93 Hz, 2 H), 1.31 - 1.45 (m, 8 H), 1.06 (t, J=7.14 Hz, 3 H). Method 1, retention time, 4.995 min; Method 2, retention time 3.281 min; HRMS: m/z (M⁺) = 395.1623 (Calculated for Ci₉H₂₆ClN₃0₄ = 395.1612). Solubility (PBS, pH 7.4, 23 °C) = >75.0 μg/mL.

EXAMPLE 6

[0101] This example illustrates the functional bioactivity of inventive compounds of Formula I, in accordance with an embodiment, using the primary qHTS assay for lipid storage modulators as described in Example 1. The results are set forth in Table 1.

Table 1

S3-cell

Entry Internal ID SID CID R' R" X, X'

ECso (μΜ)

1 MLS001082600-01 49718881 24790493 0

2 MLS001100821-01 49736971 24793951

MLS001090699-01 49737230 24794037

4 MLS00110051 1-01 49737431 24794160 ( ^ ^" ^Γ^^{' Η} _' ^{H 0}'¹³⁰

5 MLS001 101058-01 49818319 24817304 P^~ ( ^ H, H >50

6 MLS001126766-01 49825755 18524032 H, H 0.140

7 MLS001121852-01 49826252 24819270 H, H 0.010

8 NCGC00189332-01 99381516 16192366 H, H 0.009

9 NCGC00189555-01 99381576 42288156 H, H 0.008

10 NCGC00189556-01 99381577 42288155 H, H 7.91 1

1 1 NCGC00238536-01 99381578 46916324 H, H 7.91 1

12 NCGC00238537-01 99381579 46916310 H, H 0.056

13 NCGC00238539-01 99381581 24794296 H, H 0.016

Compound NCGC00238554-01 is fully aromatic. EXAMPLE 7

[0102] This example illustrates the functional bioactivity of inventive compounds of Formula II, in accordance with an embodiment, using the primary qHTS assay for lipid storage modulators as described in Example 1. The results are set forth in Table 2.

Table 2

S3-cell

Entry Internal ID SID CID R', R" R'

EC₅₀ (μΜ)

14 NCGC00241425-01 99460852 46947846 OEt, OEt 0.353

15 NCGC00241424-01 99460853 46947859 OEt, OEt 0.079

16 NCGC00241431-01 99460854 46947858 OEt, OEt 0.028

17 NCGC00241441-01 99460855 8106251 OEt, OEt 0.560

18 NCGC00241417-01 99460864 8781314 OEt, OEt >50

19 NCGC00241415-01 99460866 728907 OEt, OEt >50

20 NCGC00241423-01 99460870 6619052 OEt, OEt 11.175

21 NCGC00241420-01 99460871 46947844 OEt, OEt

>50

22 NCGC00241414-01 99460872 46947864 OEt, OEt - . >50

23 NCGC00241413-01 99460874 46947862 OEt, OEt -$- e >50

24 NCGC00241445-01 99460883 46947842 -CH,0-CH, >50

25 NCGC00241453-01 99460889 46947848 OH, OH >50

EXAMPLE 8

[0103] This example illustrates the functional bioactivity of inventive compounds of Formula III, in accordance with an embodiment, using the primary qHTS assay for lipid storage modulators as described in Example 1. The results are set forth in Table 3. Table 3

EXAMPLE 9

[0104] This example sets forth characterization data for several representative embodiments of the invention.

[0105] NCGC00238537 (LLI01-002)

N-(l-(2,4-difluorophenyl)-4,5,6,7-tetrahydro-lH-indazol-4-yl)benzamide

1H NMR (400 MHz, DMSO- 6) δ ppm 8.67 (d, J=7.63 Hz, 1 H), 7.88 - 7.94 (m, 2 H), 7.40 - 7.62 (m, 6 H), 7.23 - 7.31 (m, 1 H), 5.13 - 5.22 (m, 1 H), 2.50 (dt, J=3.42, 1.81 Hz, 2 H), 1 .94 - 2.03 (m, 2 H), 1.72 - 1.80 (m, 2 H); Method 1 , retention time: 5.440 min; HRMS: m/z (M+H)⁺ = 354.1414 (Calculated for C₂₀Hi₈F₂N₃O - 354.1412).

[0106] NCGC00238560 (LLIOl -01 1)

N-(l-(2,4-difluorophenyl)-4,5,6,7-tetrahydro-lH-indazol-4-yl)-l,2,5-oxadiazoIe-3- carboxamide

Ή NMR (400 MHz, DMSO-i/6) δ ppm 8.76 (d, J=8.22 Hz, 1 H), 7.52 - 7.61 (m, 4 H), 7.23 - 7.30 (m, 1 H), 5.00 - 5.09 (m, 1 H), 2.41 - 2.48 (m, 2 H), 1.87 - 1.98 (m, 2 H), 1.68 - 1.78 (m, 2 H); Method 1 , retention time: 4.969 min; HRMS: m/z (M+H)⁺ = 346.1 1 12 (Calculated for Ci₆H₁₄F2N502 = 346.1 1 10).

[0107] NCGC00238547 (LLI01-012) N-(l-(2,4-difluorophenyl)-4,5,6,7-tetrahydro-lH-indazol-4-yl)cyclopropanecarboxamide

Ή NMR (400 MHz, DMSO- 6) 5 ppm 8.37 (d, J=7.83 Hz, 1 H), 7.50 - 7.63 (m, 3 H), 7.22 - 7.31 (m, J=8.56, 8.56, 2.84, 1.57 Hz, 1 H), 4.85 - 4.94 (m, 1 H), 2.45 (q, J=5.74 Hz, 2 H), 1.80 - 1.90 (m, 2 H), 1.67 - 1.78 (m, 1 H), 1.54 - 1.64 (m, 2 H), 0.58 - 0.77 (m, 4 H); Method 1 , retention time: 4.870 min; HRMS: m/z (M+H)⁺ = 318.1416 (Calculated for Ci₇Hi8F₂N₃0 = 318.1412).

[0108] NCGC00238548 (LLI01-013)

N-(l-(2,4-difluorophenyl)-4,5,6,7-tetrahydro-lH-indazol-4-yl)thiophene-2-carboxamide

Ή NMR (400 MHz, DMSO-i/6) δ ppm 8.72 (d, J=8.22 Hz, 1 H), 7.87 (dd, J=3.91 , 1.17 Hz, 1 H), 7.75 (dd, J=4.70, 1.17 Hz, 1 H), 7.52 - 7.63 (m, 3 H), 7.22 - 7.31 (m, J=8.56, 8.56, 2.84, 1.17 Hz, 1 H), 7.13 (dd, J=4.89, 3.72 Hz, 1 H), 5.08 - 5.17 (m, 1 H), 2.49 (br. s., 2 H), 1.92 - 2.03 (m, 2 H), 1.67 - 1.82 (m, 2 H); Method 1 , retention time: 5.386 min; HRMS: m/z (M+H)⁺ = 360.0979 (Calculated for Ci₈Hi₆F₂N₃OS = 360.0977).

[0109] NCGC00238559 (LLI01-014)

N-(l-(2,4-difluorophenyl)-4,5,6,7-tetrahydro-lH-indazol-4-yl)thiophene-3-carboxamide

Ή NMR (400 MHz, DMSO-J6) 5ppm 8.50 (d, J=8.22 Hz, 1 H), 8.22 (dd, J=2.74, 1.57 Hz, 1 H), 7.52 - 7.63 (m, 5 H), 7.22 - 7.31 (m, 1 H), 5.09 - 5.18 (m, 1 H), 3.34 - 3.45 (m, 2 H), 1.92

- 2.02 (m, 2 H), 1.74 (td, J=10.86, 6.46 Hz, 2 H); Method 1 , retention time: 5.321 min;

HRMS: m/z (M+H)⁺ = 360.0978 (Calculated for C,₈Hi₆F₂N₃OS = 360.0977).

[0110] NCGC00238557 (LLI01-015)

4-Benzoyl-N-(l-(2,4-difluorophenyl)-4,5,6,7-tetrahydro-lH-indazol-4-yl)benzamide

Ή NMR (400 MHz, DMSO- 6) δρριη 8.89 (d, J=8.22 Hz, 1 H), 8.01 - 8.10 (m, 2 H), 7.65 - 7.83 (m, 5 H), 7.50 - 7.64 (m, 5 H), 7.20 - 7.30 (m, 1 H), 5.18 (td, J=2.25, 0.98 Hz, 1 H), 2.40

- 2.56 (m, 2 H), 1.92 - 2.04 (m, 2 H), 1.69 - 1.84 (m, 2 H); Method 1 , retention time: 6.071 min; HRMS: m/z (M+H)⁺ = 458.1680 (Calculated for C27H22F2N3O2 = 458.1675).

[0111] NCGC00238558 (LLI01-016) tert-Butyl 2-(l-(2,4-difluorophenyI)-4,5,6,7-tetrahydro-lH-indazol-4- ylcarbamoyl)piperidine-l-carboxylate

Ή NMR (400 MHz, DMSO- 6) δ ppm 8.00 - 8.14 (m, 1 H), 7.43 - 7.63 (m, 3 H), 7.22 - 7.31 (m, 1 H), 4.86 - 4.96 (m, 1 H), 4.39 - 4.60 (m, 1 H), 3.79 (dd, J=l 1.54, 0.98 Hz, 1 H), 3.07 - 3.31 (m, 2 H), 2.39 - 2.48 (m, 2 H), 1.95 - 2.08 (m, 1 H), 1.80 - 1.94 (m, 2 H), 1.48 - 1.79 (m, 5 H), 1.19 - 1.46 (m, 10 H); Method 1 , retention time: 6.095 min; HRMS: m/z (M+H)⁺ = 461.2367 (Calculated for C₂₄H3₁F₂N₄O₃ = 461.2359).

[0112] NCGC00238556 (LLI01-018)

N-(l-(2,4-difluorophenyl)-4,5,6,7-tetrahydro-lH-indazol-4-yl)isonicotinamide

Ή NMR (400 MHz, DMSO-J6) δ ppm 9.05 (d, J=7.83 Hz, 1 H), 8.77 (d, J=5.87 Hz, 2 H), 7.91 (d, J=6.26 Hz, 2 H), 7.51 - 7.66 (m, 3 H), 7.23 - 7.32 (m, 1 H), 5.12 - 5.23 (m, 1 H), 2.48 - 2.59 (m, 2 H), 1.99 (dd, J=10.17, 3.52 Hz, 2 H), 1.70 - 1.83 (m, 2 H); Method 1 , retention time: 3.993 min; HRMS: m/z (M+H)⁺ = 355.1367 (Calculated for Ci9H₁₇F₂N₄0 = 355.1365).

[0113] NCGC00238550 (LLI01-020)

N-(3,4-diethoxyphenethyl)-4-isopropyl-4H-thieno[3,2-b]pyrrole-5-carboxamide

Ή NMR (400 MHz, DMSO- 6) δ ppm 8.25 (t, J=5.48 Hz, 1 H), 7.41 (d, J=5.09 Hz, 1 H), 7.30 (d, J=5.87 Hz, 1 H), 6.83 - 6.88 (m, 2 H), 6.82 (d, J=l .96 Hz, 1 H), 6.72 (dd, J=8.22, 1.96 Hz, 1 H), 5.59 (dt, J=13.79, 6.99 Hz, 1 H), 3.97 (qd, J=6.98, 4.50 Hz, 4 H), 3.37 - 3.44 (m, 2 H), 2.74 (t, J=7.24 Hz, 2 H), 1.44 (d, J=6.65 Hz, 6 H), 1.29 (td, J=6.95, 2.15 Hz, 6 H)Method 1, retention time: 6.439 min; HRMS: m/z (M+H)⁺ = 401.1899 (Calculated for C₂₂H₂9N₂0₃S = 401.1893).

[0114] NCGC00092589 (LLI01-021)

N-(3,4-diethoxyphenethyl)-4-methyl-4H-thieno[3,2-b]pyrrole-5-carboxamide

Ή NMR (400 MHz, DMSO-i 6) δ ppm 8.24 (t, J=5.67 Hz, 1 H), 7.43 (d, J=5.48 Hz, 1 H), 7.18 (d, J=5.87 Hz, 1 H), 7.02 (s, 1 H), 6.79 - 6.88 (m, 2 H), 6.72 (dd, J=8.02, 2.15 Hz, 1 H), 3.90 - 4.02 (m, 7 H), 3.35 - 3.46 (m, 2 H), 2.74 (t, J=7.24 Hz, 2 H), 1.29 (td, J=6.95, 4.1 1 Hz,

6 H); Method 1 , retention time: 6.023 min; HRMS: m/z (M+H)⁺ = 373.1581 (Calculated for C₂0H₂5N₂O₃S = 373.1580).

[0115] NCGC00238551 (LLI01-022)

4-Benzyl-N-(3,4-diethoxyphenethyl)-4H-thieno[3,2-b]pyrrole-5-carboxamide

Ή NMR (400 MHz, DMSO-i/6) δ ppm 8.31 (t, J=5.58 Hz, 1 H), 7.41 (d, J=5.28 Hz, 1 H), 7.17 - 7.29 (m, 3 H), 7.10 - 7.17 (m, 3 H), 7.08 (s, 1 H), 6.82 (d, J=8.22 Hz, 1 H), 6.79 (d, J=l .96 Hz, 1 H), 6.68 (dd, J=8.22, 1.96 Hz, 1 H), 5.78 (s, 2 H), 3.95 (qd, J=6.98, 3.52 Hz, 4 H), 3.36 - 3.44 (m, 2 H), 2.72 (t, J=7.24 Hz, 2 H), 1.28 (dt, J=9.88, 6.99 Hz, 6 H); Method 1 , retention time: 6.671 min; HRMS: m/z (M+H)⁺ = 449.1904 (Calculated for C2₆H29N₂O3S = 449.1910). [0116] NCGC00238549 (LLI01-023)

N-(3,4-dimethoxybenzyl)-4-ethyl-4H-thieno[3,2-b]pyrrole-5-carboxamide

Method 1 , retention time: 5.587 min.

[0117] NCGC00238552 (LLI01-025)

N-(l-(2,4-difluorophenyl)-4,5,6,7-tetrahydro-lH-indazol-4-yl)cyclohexanecarboxamide

1H NMR (400 MHz, DMSO- 6) 5ppm 7.96 (d, J=7.83 Hz, 1 H), 7.51 - 7.64 (m, 2 H), 7.48 (s,

1 H), 7.20 - 7.30 (m, 1 H), 4.80 - 4.92 (m, 1 H), 2.36 - 2.47 (m, 2 H), 2.13 (tt, =1 1.59, 3.28 Hz, 1 H), 1.79 - 1.95 (m, 2 H), 1.48 - 1.77 (m, 7 H), 1.30 - 1.45 (m, 2 H), 1.10 - 1.27 (m, 3 H); Method 1 , retention time: 5.679 min.

[0118] NCGC00238553 (LLI01-026)

N-(l-(2,4-difluorophenyl)-4,5,6,7-tetrahydro-lH-indazol-4-yl)-lH-pyrazole-3- carboxamide

Ή NMR (400 MHz, DMSO- 6) δ ppm 7.91 - 8.03 (m, 1 H), 7.46 - 7.67 (m, 3 H), 7.20 - 7.34 (m, 2 H), 6.69 (t, J=2.15 Hz, 1 H), 5.05 - 5.17 (m, 1 H), 4.64 - 4.79 (m, 1 H), 2.50 - 2.62 (m,

2 H), 1.88 - 2.09 (m, 2 H), 1.65 - 1.87 (m, 2 H); Method 1, retention time: 4.559 min; HRMS: m/z (M+H)⁺ = 344.1317 (Calculated for C,₇Hi₆F₂N₅0 = 344.1317).

[0119] NCGC00238539 (LLI01-030)

N-(l-(2,4-difluorophenyl)-4,5,6,7-tetrahydro-lH-indazol-4-yl)-3-methyl-5,6-dihydro-l,4- dioxine-2-carboxamide

1H NMR (400 MHz, DMSO-^6) δ ppm 7.49 - 7.63 (m, 3 H), 7.44 (d, J=8.22 Hz, 1 H), 7.21 - 7.30 (m, J=8.51 , 8.51 , 2.74, 1.37 Hz, 1 H), 4.91 - 5.03 (m, 1 H), 4.09 (t, J=3.91 Hz, 2 H), 3.99 (q, J=3.65 Hz, 2 H), 2.38 - 2.48 (m, 2 H), 2.16 - 2.22 (m, 3 H), 1.80 - 1.96 (m, 2 H), 1.71 (ddd, J=l 1 .54, 6.06, 5.87 Hz, 2 H); Method 1 , retention time: 5.379 min; HRMS: m/z (M+H)⁺ = 376.1468 (Calculated for C₁₉H₂oF₂N₃0₃ = 376.1467).

[0120] NCGC00238554 (LLI01-046_2^,ul)

N-(l-(4-fluorophenyl)-lH-indazol-4-yl)picolinamide

'H MR (400 MHz, DMSO-i 6) δ ppm 10.94 (s, 1 H), 8.82 (dt, J=4.84, 0.81 Hz, 1 H), 8.48 (s, 1 H), 8.23 (dd, J=7.73, 0.88 Hz, 1 H), 8.06 - 8.16 (m, 1 H), 7.70 - 7.85 (m, 4 H), 7.56 - 7.62 (m, 1 H), 7.41 - 7.55 (m, 3 H); Method 1 , retention time: 6.170 min.

[0121] NCGC00238541 (LLI01-050) N-(l-(2,4-difluorophenyl)-4,5,6,7-tetrahydro-lH-indazol-4-yl)pyrazine-2-carboxamide

1H NMR (400 MHz, DMSO- 6) δ ppm 9.24 (d, J=l .37 Hz, 1 H), 8.87 (d, J=2.54 Hz, 1 H), 8.83 (d, J=8.22 Hz, 1 H), 8.72 (dt, J=2.54, 1.27 Hz, 1 H), 7.51 - 7.65 (m, 3 H), 7.22 - 7.31 (m, 1 H), 5.14 - 5.24 (m, 1 H), 2.41 - 2.56 (m, 2 H), 1.92 - 2.02 (m, 2 H), 1.83 - 1.92 (m, 1 H), 1.71 - 1.82 (m, 1 H); Method 1, retention time: 4.971 min; HRMS: m/z (M+H)⁺ = 356.1316 (Calculated for Ci₈H₁₆F₂N₅0 = 356.1317).

[0122] NCGC00241413 (LLI01-091)

N-(3,4-diethoxyphenethyl)acetamide

1H NMR (400 MHz, DMSO-i/6)8ppm 7.93 (t, J=5.28 Hz, 1 H), 6.92 (d, J=8.22 Hz, 1 H), 6.86 (d, J=1.96 Hz, 1 H), 6.75 (dd, J=8.02, 2.15 Hz, 1 H), 4.06 (dq, J=12.33, 6.98 Hz, 4 H), 3.24 - 3.34 (m, 2 H), 2.68 (t, J=7.43 Hz, 2 H), 1.86 (s, 3 H), 1.39 (td, J=6.85, 5.87 Hz, 6 H); Method 1 , retention time: 4.369 min; HRMS: m/z (M+H)⁺ = 252.1592 (Calculated for C₁₄H₂₂N0₃ = 252.1594).

[0123] NCGC00241414 (LLI01-094)

N-(3,4-diethoxyphenethyl)-2-(dimethylamino)acetamide

1H NMR (400 MHz, DMSO- 6) δ ppm 8.44 - 8.52 (m, 1 H), 6.84 (d, J=7.83 Hz, 1 H), 6.80 (d, J=1.96 Hz, 1 H), 6.69 (dd, J-8.02, 2.15 Hz, 1 H), 3.98 (dq, J=14.09, 7.04 Hz, 4 H), 3.76 (br. s., 2 H), 3.32 - 3.39 (m, 2 H), 2.71 (s, 6 H), 2.66 (t, J=7.24 Hz, 2 H), 1.30 (dt, J=8.12, 6.90 Hz, 6 H); Method 1, retention time: 3.528 min; HRMS: m/z (M+H)⁺ = 295.2016

(Calculated for Ci₆H₂₇N₂0₃ = 295.2016).

[0124] NCGC00241415 (LLI01-095)

N-(3,4-diethoxyphenethyl)thiophene-2-carboxamide

Ή NMR (400 MHz, DMSO-d6) δ ppm 8.52 (t, J=5.48 Hz, 1 H), 7.72 (ddd, J=5.87, 4.50, 0.98 Hz, 2 H), 7.04 - 7.21 (m, 1 H), 6.85 (d, J=7.83 Hz, 1 H), 6.80 (d, J=l .96 Hz, 1 H), 6.71 (dd, J=8.02, 2.15 Hz, 1 H), 3.91 - 4.01 (m, 4 H), 3.37 - 3.46 (m, 2 H), 2.74 (t, J=7.43 Hz, 2 H), 1.29 (td, J=7.04, 3.52 Hz, 6 H); Method 1 , retention time: 5.343 min; HRMS: m/z (M+H)⁺ = 320.1316 (Calculated for Ci₇H₂₂N0₃S = 320.1315).

[0125] NCGC00241416 (LLI01-096)

N-(3,4-diethoxyphenethyl)-l,2,5-oxadiazole-3-carboxamide

Ή NMR (400 MHz, DMSO- 6) δ ppm 8.50 (t, J=5.87 Hz, 1 H), 6.84 (d, J=7.83 Hz, 1 H), 6.77 (d, J=1 .96 Hz, 1 H), 6.68 (dd, J=8.22, 1.96 Hz, 1 H), 3.97 (quin, J=7.14 Hz, 4 H), 3.34 - 3.42 (m, 2 H), 2.70 (t, J=7.43 Hz, 2 H), 1.30 (td, J=7.04, 3.91 Hz, 6 H); Method 1 , retention time: 4.927 min; HRMS: m/z (M+H)⁺ = 306.1449 (Calculated for Ci₅H₂₀N₃O₄ = 306.1448).

[0126] NCGC00241417 (LLIOl-097)

N-(3,4-diethoxyphenethyl)benzamide

Ή NMR (400 MHz, DMSO-J6) δ ppm 8.50 (t, J=5.48 Hz, 1 H), 7.78 - 7.85 (m, 2 H), 7.48 - 7.55 (m, 1 H), 7.41 - 7.48 (m, 2 H), 6.85 (d, J=8.22 Hz, 1 H), 6.81 (d, J=1.96 Hz, 1 H), 6.72 (dd, J=7.83, 1.96 Hz, 1 H), 3.96 (q, J=7.04 Hz, 4 H), 3.41 - 3.49 (m, 2 H), 2.76 (t, J=7.43 Hz, 2 H), 1.29 (td, J=7.04, 3.13 Hz, 6 H); Method 1, retention time: 5.409 min; HRMS: m/z (M+H)⁺ = 314.1752 (Calculated for Ci₉H₂₄N0₃ = 314.1751).

[0127] NCGC00241418 (LLI01-098)

N-(3,4-diethoxyphenethyl)-3-methyl-5,6-dihydro-l,4-dioxine-2-carboxamide

Ή NMR (400 MHz, DMSO-c/6) δ ppm 7.54 (t, J=5.87 Hz, 1 H), 6.84 (d, J=8.22 Hz, 1 H),

6.76 (d, J=1.96 Hz, 1 H), 6.67 (dd, J=8.22, 1.96 Hz, 1 H), 4.05 - 4.10 (m, 2 H), 3.91 - 4.03 (m, 6 H), 3.24 - 3.31 (m, 2 H), 2.60 - 2.69 (m, 2 H), 2.15 (s, 3 H), 1.25 - 1.35 (m, 6 H);

Method 1, retention time: 5.369 min; HRMS: m/z (M+H)⁺ = 336.1811 (Calculated for C₁₈H₂₆N0₅ = 336.1805).

[0128] NCGC00241419 (LLI01-099)

N-(3,4-diethoxyphenethyl)picolinamide

Ή NMR (400 MHz, DMSO-rf6) δ ppm 8.75 (t, J=6.06 Hz, 1 H), 8.62 (td, J=2.93, 1.57 Hz, 1 H), 7.93 - 8.06 (m, 2 H), 7.56 - 7.65 (m, 1 H), 6.84 (d, J=8.22 Hz, 1 H), 6.81 (d, J=1.96 Hz, 1 H), 6.72 (dd, J=8.02, 2.15 Hz, 1 H), 3.96 (qd, J=6.91 , 2.74 Hz, 4 H), 3.45 - 3.56 (m, 2 H),

2.77 (t, J=7.43 Hz, 2 H), 1.28 (q, J=6.91 Hz, 6 H); Method 1 , retention time: 5.345 min; HRMS: m/z (M+H)⁺ = 315.1707 (Calculated for Ci₈H₂₃N₂0₃ = 315.1703).

[0129] NCGC00241420 (LLI02-001)

N-(3,4-diethoxyphenethyI)-2-phenylacetamide

Ή NMR (400 MHz, DMSO-J6) δ ppm 8.04 (t, J=5.48 Hz, 1 H), 7.24 - 7.30 (m, 2 H), 7.17 - 7.23 (m, 3 H), 6.82 (d, J=7.83 Hz, 1 H), 6.75 (d, J=1.96 Hz, 1 H), 6.64 (dd, J=8.02, 2.15 Hz,

1 H), 3.96 (qd, J=6.91 , 4.30 Hz, 4 H), 3.37 (s, 2 H), 3.20 - 3.28 (m, 2 H), 2.61 (t, J=7.24 Hz,

2 H), 1.29 (t, J=6.85 Hz, 6 H); Method 1 , retention time: 5.342 min; HRMS: m/z (M+H)⁺ = 328.1910 (Calculated for C₂₀H₂₆NO₃ = 328.1907).

[0130] NCGC00241421 (LLI02-002) N-(3,4-diethoxyphenethyl)-l-phenylcyclopropanecarboxamide

Ή NMR (400 MHz, DMSO-c 6) δ ppm 7.24 - 7.35 (m, 5 H), 6.79 (d, J=7.83 Hz, 1 H), 6.67 (d, J=1.96 Hz, 1 H), 6.54 (dd, J=8.02, 2.15 Hz, 1 H), 6.45 (t, J=5.67 Hz, 1 H), 3.96 (qd, J=6.91 , 5.48 Hz, 4 H), 3.15 - 3.25 (m, 2 H), 2.54 (t, J=7.24 Hz, 4 H), 1.26 - 1.34 (m, 6 H), 0.93 (q, J=3.52 Hz, 2 H); Method 1, retention time: 6.036 min; HRMS: m/z (M+H)⁺ = 354.2067 (Calculated for C₂₂H₂₈N0₃ = 354.2064).

[0131] NCGC00241422 (LLI02-003)

N-(3,4-diethoxyphenethyl)benzofuran-2-carboxamide

Ή NMR (400 MHz, DMSO- 6) δ ppm 8.74 (t, J=5.87 Hz, 1 H), 7.76 (dt, J=7.83, 0.98 Hz, 1 H), 7.59 - 7.68 (m, 1 H), 7.50 (d, J=0.78 Hz, 1 H), 7.42 - 7.49 (m, 1 H), 7.33 (td, J=7.53, 0.98 Hz, 1 H), 6.79 - 6.88 (m, 2 H), 6.72 (dd, J=8.02, 2.15 Hz, 1 H), 3.96 (q, J=7.04 Hz, 4 H), 3.43 - 3.52 (m, 2 H), 2.77 (t, J=7.43 Hz, 2 H), 1.27 (dt, J=12.03, 6.90 Hz, 6 H); Method 1 , retention time: 5.870 min; HRMS: m/z (M+H)⁺ = 354.1704 (Calculated for C₂,H₂₄N0₄ = 354.1700).

[0132] NCGC00251423 (LLI02-004)

N-(3,4-diethoxyphenethyl)-2,3-dihydrobenzo[b] [l,4]dioxine-2-carboxamide

Ή NMR (400 MHz, DMSO-c 6) 6 ppm 8.12 (t, J=5.67 Hz, 1 H), 6.93 - 6.97 (m, 1 H), 6.84 - 6.91 (m, 3 H), 6.81 (d, J=8.22 Hz, 1 H), 6.76 (d, J=1.96 Hz, 1 H), 6.62 (dd, J=8.02, 2.15 Hz, 1 H), 4.73 (dd, J=6.26, 2.74 Hz, 1 H), 4.30 (dd, J=l 1.35, 2.74 Hz, 1 H), 4.14 (dd, J=l 1.35, 6.26 Hz, 1 H), 3.97 (quin, J=7.04 Hz, 4 H), 3.27 - 3.37 (m, 2 H), 2.64 (t, J=7.24 Hz, 2 H), 1.29 (t, J=6.85 Hz, 6 H); Method 1, retention time: 5.809 min.

[0133] NCGC00241424 (LLI02-005)

N-(3,4-diethoxyphenethyl)-4-(3-methylbut-2-enyl)-4H-thieno[3,2-b]pyrrole-5- carboxamide

Ή NMR (400 MHz, DMSO-c/6) 5 ppm 8.23 (t, J=5.67 Hz, 1 H), 7.42 (d, J=5.09 Hz, 1 H), 7.08 (d, J=5.87 Hz, 1 H), 6.98 (s, 1 H), 6.78 - 6.88 (m, 2 H), 6.71 (dd, J=8.22, 1.96 Hz, 1 H), 5.18 - 5.27 (m, 1 H), 5.1 1 (d, J=7.04 Hz, 2 H), 3.96 (q, J=7.04 Hz, 4 H), 3.36 - 3.46 (m, 2 H), 2.74 (t, J=7.24 Hz, 2 H), 1.77 (s, 3 H), 1.64 (s, 3 H), 1.28 (q, J=7.04 Hz, 6 H); Method 1 , retention time: 6.748 min; HRMS: m/z (M+H)⁺ = 427.2058 (Calculated for C24H31 N2O3S = 427.2050).

[0134] NCGC00241425 (LLI02-006) N-(3,4-diethoxyphenethyl)-4-(pyridin-3-ylmethyl)-4H-thieno[3,2-b]pyrrole-5- carboxamide

Ή NMR (400 MHz, DMSO- 6) δ ppm 8.44 - 8.51 (m, 2 H), 8.35 (t, J=5.67 Hz, 1 H), 7.53 - 7.60 (m, 1 H), 7.46 (d, J=5.48 Hz, 1 H), 7.37 (dd, J=7.63, 4.89 Hz, 1 H), 7.25 (d, J=5.48 Hz, 1 H), 7.13 (s, 1 H), 6.83 (d, J=8.22 Hz, 1 H), 6.79 (d, J=1.96 Hz, 1 H), 6.68 (dd, J=7.83, 1.96 Hz, 1 H), 5.82 (s, 2 H), 3.95 (qd, J=6.91 , 5.09 Hz, 4 H), 3.41 - 3.51 (m, 2 H), 2.72 (t, J=7.43 Hz, 2 H), 1.28 (dt, J=10.66, 6.99 Hz, 6 H); Method 1 , retention time: 4.617 min; HRMS: m/z (M+H)⁺ = 450.1855 (Calculated for C₂5H28N₃0₃S = 450.1846).

[0135] NCGC00241426 (LLI02-007)

N-(3,4-diethoxyphenethyl)-4-(3-methylbenzyl)-4H-thieno[3,2-b]pyrrole-5-carboxamide

Ή NMR (400 MHz, DMSO- 6) δ ppm 8.29 (t, J=5.67 Hz, 1 H), 7.39 (d, J=5.48 Hz, 1 H), 7.08 - 7.15 (m, 2 H), 7.04 (s, 1 H), 6.96 - 7.02 (m, 2 H), 6.87 (d, J=7.43 Hz, 1 H), 6.75 - 6.83 (m, 2 H), 6.66 (dd, J=8.22, 1.96 Hz, 1 H), 5.71 (s, 2 H), 3.93 (qd, J=6.98, 4.70 Hz, 4 H), 3.34 - 3.43 (m, 2 H), 2.70 (t, J=7.24 Hz, 2 H), 2.19 (s, 3 H), 1.25 (dt, J=10.27, 6.90 Hz, 6 H); Method 1, retention time: 6.81 1 min; HRMS: m/z (M+H)⁺ = 463.2057 (Calculated for C₂₇H₃₁N₂0₃S = 463.2050).

[0136] NCGC00241427 (LLI02-008)

N-(3,4-diethoxyphenethyl)-4-(2,4-difluorobenzyl)-4H-thieno[3,2-b]pyrrole-5- carboxamide

1H NMR (400 MHz, DMSO- 6) δ ppm 8.32 (t, J=5.67 Hz, 1 H), 7.44 (d, J=5.48 Hz, 1 H), 7.23 (ddd, J=10.56, 9.39, 2.54 Hz, 1 H), 7.07 - 7.16 (m, 2 H), 6.90 - 7.02 (m, 1 H), 6.74 - 6.87 (m, 3 H), 6.67 (dd, J=8.12, 2.05 Hz, 1 H), 5.80 (s, 2 H), 3.95 (qd, J=6.98, 3.33 Hz, 4 H), 3.34 - 3.43 (m, 2 H), 2.70 (t, J=7.34 Hz, 2 H), 1.28 (dt, J= 10.03, 7.02 Hz, 6 H); Method 1 , retention time: 6.765 min; HRMS: m/z (M+H)⁺ = 485.1708 (Calculated for C₂6H₂₇F₂N₂0₃S = 485.1705).

[0137] NCGC00241428 (LLI02-009)

N-(3,4-diethoxyphenethyl)-4-(4-(difluoromethoxy)benzyI)-4H-thieno[3,2-b]pyrroIe-5- carboxamide

Ή NMR (400 MHz, DMSCW6) δ ppm 8.28 - 8.34 (m, 1 H), 7.32 - 7.51 (m, 1 H), 7.14 - 7.23 (m, 3 H), 7.05 - 7.10 (m, 1 H), 6.95 - 6.99 (m, 1 H), 6.76 - 6.86 (m, 3 H), 6.69 (ddd, J=7.92, 4.01 , 1.37 Hz, 2 H), 5.73 - 5.79 (m, 2 H), 3.94 (dd, J=12.13, 7.04 Hz, 4 H), 3.38 - 3.45 (m, 2 H), 2.82 - 2.89 (m, 2 H), 1.24 - 1.33 (m, 6 H); Method 1 , retention time: 6.664 min; HRMS: m/z (M+H)⁺ = 515.1814 (Calculated for C₂₇H₂₉F₂N₂0₄S = 515.181 1 ).

[0138] NCGC00241429 (LLI02-010)

4-(4-Chloro-3-fluorobenzyl)-N-(3,4-diethoxyphenethyl)-4H-thieno[3,2-b]pyrrole-5- carboxamide

Ή NMR (400 MHz, DMSO-d6) δ ppm 8.35 (t, J=5.67 Hz, 1 H), 7.49 (t, J=8.02 Hz, 1 H), 7.45 (d, J-5.48 Hz, 1 H), 7.15 - 7.22 (m, 2 H), 7.13 (s, 1 H), 6.93 (dd, J=8.22, 1.57 Hz, 1 H), 6.82 (d, J=7.83 Hz, 1 H), 6.79 (d, J=1.96 Hz, 1 H), 6.66 (dd, J=8.22, 1.96 Hz, 1 H), 5.77 (s, 2 H), 3.95 (qd, J=7.04, 5.09 Hz, 4 H), 3.37 - 3.44 (m, 2 H), 2.72 (t, J=7.24 Hz, 2 H), 1.27 (dt, J=12.42, 6.90 Hz, 6 H); Method 1 , retention time: 6.951 min; HRMS: m/z (M+H)⁺ =

501.1417 (Calculated for C₂₆H₂₇C1FN₂0₃S = 501.1409).

[0139] NCGC00241430 (LLI02-011)

4- (4-(lH-l,2,4-triazol-l-yl)benzyl)-N-(3,4-diethoxyphenethyl)-4H-thieno[3,2-b]pyrrole-

5- carboxamide

1H NMR (400 MHz, DMSO- 6) δ ppm 9.20 (s, 1 H), 8.33 (t, J=5.67 Hz, 1 H), 8.20 (s, 1 H), 7.74 (d, J=8.61 Hz, 2 H), 7.44 (d, J=5.09 Hz, 1 H), 7.30 (d, J=8.61 Hz, 2 H), 7.21 (d, J=5.48 Hz, 1 H), 7.1 1 (s, 1 H), 6.77 - 6.84 (m, 2 H), 6.67 (dd, J=8.22, 1.96 Hz, 1 H), 5.83 (s, 2 H), 3.89 - 3.98 (m, 4 H), 3.36 - 3.45 (m, 2 H), 2.73 (t, J=7.04 Hz, 2 H), 1.21 - 1.31 (m, 6 H); Method 1 , retention time: 5.994 min; HRMS: m/z (M+H)⁺ = 516.2062 (Calculated for C_2gH₃oN₅0₃S = 516.2064).

[0140] NCGC00241431 (LLI02-012)

N-(3,4-diethoxyphenethyl)-4-phenethyl-4H-thieno[3,2-b]pyrrole-5-carboxamide

Ή NMR (400 MHz, DMSO-i/6) δ ppm 8.23 (t, J-5.67 Hz, 1 H), 7.36 (d, J=5.48 Hz, 1 H), 7.21 - 7.27 (m, 2 H), 7.14 - 7.21 (m, 2 H), 7.06 (d, J=5.87 Hz, 1 H), 7.03 (s, 1 H), 6.80 - 6.86 (m, 2 H), 6.73 (dd, J=8.02, 1.76 Hz, 1 H), 6.51 (s, 1 H), 4.62 - 4.70 (m, 2 H), 3.89 - 4.00 (m, 4 H), 3.40 - 3.48 (m, 2 H), 2.90 - 2.98 (m, 2 H), 2.76 (t, J=7.24 Hz, 2 H), 1.27 (t, J=7.04 Hz, 6 H); Method 1 , retention time: 6.815 min; HRMS: m/z (M+H)⁺ = 463.2052 (Calculated for C₂₇H₃iN₂0₃S = 463.2050).

[0141] NCGC00241433 (LLI02-014)

N,4-dibenzyl-N-(3,4-dihydroxyphenethyl)-4H-thieno[3,2-b]pyrrole-5-carboxamide

Ή NMR (400 MHz, DMSO-c 6) δ ppm 1 1.65 (d, J=1.56 Hz, 2 H), 8.25 (t, J=5.67 Hz, 2 H), 7.23 - 7.51 (m, 10 H), 7.06 (dd, J=1.96, 0.78 Hz, 1 H), 6.91 - 6.99 (m, 3 H), 6.75 (dd, J=8.22, 1.96 Hz, 1 H), 5.06 (d, J=l 1.74 Hz, 3 H), 3.39 - 3.50 (m, 2 H), 2.75 (t, J=7.24 Hz, 2 H); Method 1 , retention time: 6.616 min; HRMS: m/z (M+H)⁺ = 483.1718 (Calculated for C₂ H27 20₃S = 483.1737).

[0142] NCGC00241434 (LLI02-017)

N-(3,4-diethoxyphenethyl)-l-methyl-lH-indole-2-carboxamide

Ή NMR (400 MHz, DMSO-d6) 8 ppm 8.52 (d, J=3.13 Hz, 1 H), 7.62 (dd, J=7.83, 2.74 Hz, 1 H), 7.51 (dd, J=8.02, 2.93 Hz, 1 H), 7.20 - 7.31 (m, 1 H), 7.09 (td, J=7.43, 3.13 Hz, 1 H), 7.01 (d, J=3.52 Hz, 1 H), 6.80 - 6.90 (m, 2 H), 6.74 (dd, J=8.02, 1.37 Hz, 1 H), 3.84 - 4.07 (m, 7 H), 3.45 (d, J=3.91 Hz, 2 H), 2.73 - 2.82 (m, 2 H), 1.21 - 1.37 (m, 6 H); Method 1 , retention time: 6.126 min; HRMS: m/z (M+H)⁺ = 367.2019 (Calculated for C₂₂H₂₇N₂0₃ = 367.2016).

[0143] NCGC00241436 (LLI02-019) 3-Benzoyl-N-(3,4-diethoxyphenethyl)benzamide

1H NMR (400 MHz, DMSO- 6) δ ppm 8.71 (d, J=2.35 Hz, 1 H), 8.17 (br. s., 1 H), 8.10 (d, J=7.83 Hz, 1 H), 7.86 (d, J=7.43 Hz, 1 H), 7.52 - 7.80 (m, 6 H), 6.76 - 6.90 (m, 2 H), 6.70 (d, J=7.83 Hz, 1 H), 3.95 (qd, J=6.91 , 2.35 Hz, 4 H), 3.39 - 3.53 (m, 2 H), 2.70 - 2.82 (m, 2 H), 1.15 - 1.46 (m, J=7.24, 7.24, 7.04, 2.35 Hz, 6 H); Method 1, retention time: 6.047 min;

HRMS: m/z (M+H)⁺ = 418.201 1 (Calculated for C₂₆H₂₈N0₄ = 418.2013).

[0144] NCGC00241436 (LLI02-024)

N-(3,4-diethoxyphenethyl)quinoline-2-carboxamide

Ή NMR (400 MHz, DMSO-c/6) 5 ppm 8.85 - 8.97 (m, 1 H), 8.57 (t, J=7.83 Hz, 1 H), 8.04 - 8.20 (m, 3 H), 7.83 - 7.93 (m, 1 H), 7.67 - 7.77 (m, 1 H), 6.81 - 6.92 (m, 2 H), 6.72 - 6.80 (m, 1 H), 3.87 - 4.04 (m, J=13.25, 6.85, 6.85, 6.70 Hz, 4 H), 3.52 - 3.64 (m, 2 H), 2.84 (q, J=6.91 Hz, 2 H), 1.17 - 1.38 (m, 6 H); Method 1 , retention time: 6.183 min; HRMS: m/z (M+H)⁺ = 365.1863 (Calculated for C22H25N2O3 = 365.1860).

[0145] NCGC00241436 (LLI02-025)

N-(3,4-diethoxyphenethyl)-5,6-dihydro-4H-cyclopenta[b]thiophene-2-carboxamide

Ή NMR (400 MHz, DMSO- 6) δ ppm 8.33 (t, J=5.28 Hz, 1 H), 7.47 (s, 1 H), 6.84 (dd, J=8.22, 1.57 Hz, 1 H), 6.79 (s, 1 H), 6.69 (d, J=7.83 Hz, 1 H), 3.96 (qd, J=6.98, 1.37 Hz, 4 H), 3.39 (q, J=6.52 Hz, 2 H), 2.85 (t, J=7.04 Hz, 2 H), 2.63 - 2.76 (m, 4 H), 2.31 - 2.42 (m, J=7.29, 7.29, 7.14, 6.85 Hz, 2 H), 1.25 - 1.33 (m, 6 H); Method 1 , retention time: 5.998 min; HRMS: m/z (M+H)⁺ = 360.1633 (Calculated for C₂oH₂₆N0₃S = 360.1628).

[0146] NCGC00241436 (LLI02-029)

N-(2-(benzo [d] [ 1 ,3] dioxol-5-yl)ethyl)-4-benzyl-4H-thieno [3,2-b] pyrrole-5-carboxamide

1H NMR (400 MHz, DMSO- 6) δ ppm 8.31 (t, J=5.67 Hz, 1 H), 7.41 (d, J=5.09 Hz, 1 H), 7.17 - 7.31 (m, 3 H), 7.10 - 7.17 (m, 3 H), 7.07 (s, 1 H), 6.76 - 6.82 (m, 2 H), 6.64 (dd, J=8.02, 1.37 Hz, 1 H), 5.95 (s, 2 H), 5.78 (s, 2 H), 3.35 - 3.43 (m, 2 H), 2.72 (t, J=7.24 Hz, 2 H); Method 1 , retention time: 6.318 min; HRMS: m/z (M+H)⁺ = 405.1272 (Calculated for C₂₃H₂iN₂0₃S = 405.1267).

[0147] , NCGC00034917 (LLI02-042)

Ethyl l-(l-(3-(2-chlorophenyl)ureido)cyclohexanecarbonyl)piperidine-4-carboxylate

Ή NMR (400 MHz, DMSO- 6) δ ppm 8.20 (s, 1 H), 8.05 (dd, J=8.31, 0.88 Hz, 1 H), 7.39 (dd, J=8.02, 0.78 Hz, 1 H), 7.31 (s, 1 H), 7.16 - 7.24 (m, 1 H), 6.94 (td, J=7.68, 0.88 Hz, 1 H), 4.32 (d, J=13.30 Hz, 2 H), 3.98 (q, J=7.04 Hz, 2 H), 2.77 - 2.96 (m, 2 H), 2.51 - 2.57 (m, 1 H), 1.98 (d, J=13.50 Hz, 2 H), 1.63 - 1.82 (m, 4 H), 1.33 - 1.62 (m, 7 H), 1.14 - 1.27 (m, 1 H), 1.08 (t, J=7.04 Hz, 3 H); Method 1 , retention time: 5.516 min; HRMS: m/z (M+H)⁺ = 436.2004 (Calculated for C₂₂H₃iClN₃0₄ = 436.1998).

[0148] NCGC00241446 (LLI02-044)

Ethyl l-(l-(3-(2-chlorophenyl)ureido)cyclopropanecarbonyl)piperidine-4-carboxylate

1H NMR (400 MHz, DMSO- 6) δ ppm 8.08 (dd, J=8.22, 1.57 Hz, 1 H), 7.98 (br. s., 1 H),

7.79 (s, 1 H), 7.41 (dd, J=8.22, 1.17 Hz, 1 H), 7.24 (td, J=7.83, 1.57 Hz, 1 H), 6.98 (t, J=7.24 Hz, 1 H), 4.14 (d, J=13.30 Hz, 2 H), 4.04 (q, J=7.30 Hz, 2 H), 2.86 - 3.06 (m, 2 H), 2.54 - 2.64 (m, 1 H), 1.83 (dd, J=13.30, 2.74 Hz, 2 H), 1.36 - 1.51 (m, 2 H), 1.09 - 1.26 (m, 5 H), 0.94 (dd, J=2.93, 1.76 Hz, 2 H); Method 1 , retention time: 4.963 min; HRMS: m/z (M+H)⁺ = 394.1527 (Calculated for C,₉H₂₅C1N₃0₄ = 394.1528).

[0149] NCGC00241447 (LLI02-045)

Ethyl l-(l-(3-(2-chlorophenyl)ureido)cyclobutanecarbonyl)piperidine-4-carboxylate

Ή NMR (400 MHz, DMSO-i 6) δ ppm 8.05 (dd, J=8.61 , 1.57 Hz, 1 H), 7.91 (br. s., 1 H),

7.80 (s, 1 H), 7.39 (dd, J=8.02, 1.37 Hz, 1 H), 7.21 (ddd, J=8.41 , 7.24, 1.57 Hz, 1 H), 6.91 - 6.99 (m, 1 H), 4.15 - 4.27 (m, 1 H), 4.00 (q, J=7.04 Hz, 2 H), 3.69 - 3.83 (m, 1 H), 2.93 - 3.08 (m, 2 H), 2.66 - 2.78 (m, 1 H), 2.51 - 2.61 (m, 2 H), 2.14 (br. s., 2 H), 1.83 - 1.96 (m, 1 H), 1.74 - 1.83 (m, 2 H), 1.63 - 1.72 (m, 1 H), 1.40 (br. s., 2 H), 1.07 - 1.13 (m, 3 H); Method 1 , retention time: 5.107 min; HRMS: m/z (M+H)⁺ = 408.1690 (Calculated for C20H27CIN3O4 = 408.1685).

[0150] NCGC00241448 (LLI02-047)

Ethyl l-(l-(3-(2-chlorophenyl)ureido)cyclopentanecarbonyl)piperidine-4-carboxylate

Ή NMR (400 MHz, DMSO-c/6) δ ppm 8.06 (dd, J=8.61, 1.57 Hz, 1 H), 7.92 (s, 1 H), 7.51 (s, 1 H), 7.38 (dd, J=7.83, 1.57 Hz, 1 H), 7.21 (td, J=7.92, 1.37 Hz, 1 H), 6.94 (td, J=7.63, 1.57 Hz, 1 H), 4.19 (d, j=12.13 Hz, 2 H), 3.98 (q, J=7.30 Hz, 2 H), 3.22 (dt, J=12.62, 3.86 Hz, 1 H), 2.83 - 2.96 (m, 2 H), 2.50 - 2.59 (m, 2 H), 1.72 - 1.87 (m, 4 H), 1.55 - 1.71 (m, 4 H), 1.32 - 1.48 (m, 2 H), 1.08 (t, J=7.04 Hz, 3 H); Method 1, retention time: 5.290 min; HRMS: m/z (M+H)⁺ = 422.1844 (Calculated for C₂iH₂₉ClN₃0₄ - 422.1841).

[0151] NCGC241449 (LLI02-051)

Ethyl l-(2-(3-(2-chlorophenyl)ureido)acetyl)piperidine-4-carboxylate

Ή NMR (400 MHz, DMSO-J6) δ ppm 8.42 (s, 1 H), 8.10 (dd, J=8.41, 1.37 Hz, 1 H), 7.39 (dd, J=8.02, 1.37 Hz, 1 H), 7.28 (t, J=4.89 Hz, 1 H), 7.23 (td, J=7.92, 1.37 Hz, 1 H), 6.91 - 6.99 (m, 1 H), 4.22 (d, J=12.91 Hz, 1 H), 4.08 (q, J=7.04 Hz, 2 H), 4.01 (t, J=4.70 Hz, 2 H), 3.73 (d, J=13.69 Hz, 1 H), 3.05 - 3.15 (m, 1 H), 2.74 - 2.84 (m, 1 H), 2.56 - 2.65 (m, 1 H), 1.85 (t, J=8.80 Hz, 2 H), 1.48 - 1.61 (m, 1 H), 1.40 (dd, J=13.11, 3.33 Hz, 1 H), 1.19 (t, 3 H); Method 1 , retention time: 4.862 min.

[0152] NCGC00241450 (LLI02-054)

Ethyl l-(2-(3-(2-chlorophenyl)ureido)-2-methylpropanoyl)piperidine-4-carboxylate

Ή NMR (400 MHz, DMSO-i/6) δ ppm 8.03 (dd, J=8.41, 1.56 Hz, 1 H), 7.94 (s, 1 H), 7.42 (s, 1 H), 7.35 (dd, J=8.02, 1.37 Hz, 1 H), 7.18 (ddd, J=8.41 , 7.24, 1.57 Hz, 1 H), 6.85 - 6.96 (m, 1 H), 4.28 (dt, J=13.16, 3.30 Hz, 2 H), 3.96 (q, J=7.17 Hz, 2 H), 2.76 - 2.99 (m, 2 H), 2.43 - 2.55 (m, 1 H), 1.73 (dd, J=l 3.1 1 , 2.93 Hz, 2 H), 1.31 - 1.45 (m, 8 H), 1.06 (t, J=7.14 Hz, 3 H); Method 1 , retention time: 4.995 min; HRMS: m/z (M+H)⁺ = 396.1686 (Calculated for C 19H27CIN3O4 = 396.1685).

[0153] NCGC00241451 (LLI02-055)

N-(l-(2,4-difluorophenyl)-4,5,6,7-tetrahydro-lH-indazol-4-yl)-4-(3-(trifluoromethyl)- 3H-diazirin-3-yl)benzamide Ή NMR (400 MHz, DMSO-i½) δ ppm 8.84 (d, J=7.83 Hz, 1 H), 7.97 - 8.07 (m, 2 H), 7.51 - 7.64 (m, 3 H), 7.37 (d, J=8.22 Hz, 2 H), 7.21 - 7.32 (m, 1 H), 5.09 - 5.23 (m, 1 H), 2.45 - 2.58 (m, 2 H), 1.90 - 2.07 (m, 2 H), 1.66 - 1.85 (m, 2 H); Method 1 , retention time: 6.41 1 min; HRMS: m/z (M+H)⁺ = 462.1359 (Calculated for C2₂H₁₇F₅N₅0 = 462.1348).

[0154] NCGC00241452 (LLI02-056)

N-(3,4-diethoxyphenethyl)-4-(3-(trifluoromethyI)-3H-diazirin-3-yl)benzamide

Ή NMR (400 MHz, DMSO- 6) 5 ppm 8.65 (t, J=5.48 Hz, 1 H), 7.92 (d, J=8.61 Hz, 2 H), 7.38 (d, J=7.83 Hz, 2 H), 6.84 (d, J=8.22 Hz, 1 H), 6.79 (d, J=1.96 Hz, 1 H), 6.70 (dd, J=8.22, 1.96 Hz, 1 H), 3.95 (qd, J=6.98, 5.28 Hz, 4 H), 3.41 - 3.49 (m, 2 H), 2.75 (t, J=7.24 Hz, 2 H), 1.28 (q, J=7.04 Hz, 6 H); Method 1, retention time: 6.444 min; HRMS: m/z (M+H)⁺ = 422.1693 (Calculated for C₂₁H₂₃F₃N₃0₃ = 422.1686).

[0155] NCGC00241453 (LLI02-063)

4-Benzyl-N-(3,4-dihydroxyphenethyl)-4H-thieno[3,2-b]pyrrole-5-carboxamide

1H NMR (400 MHz, DMSO- 6) δ ppm 8.73 (s, 1 H), 8.62 (s, 1 H), 8.31 (t, J=5.67 Hz, 1 H), 7.41 (d, J=5.48 Hz, 1 H), 7.24 - 7.30 (m, 2 H), 7.19 - 7.23 (m, 1 H), 7.12 - 7.17 (m, 3 H), 7.07 (s, 1 H), 6.60 - 6.64 (m, 2 H), 6.44 (dd, J=8.02, 2.15 Hz, 1 H), 5.78 (s, 2 H), 3.32 - 3.38 (m, 2 H), 2.58 - 2.65 (m, 2 H); Method 1, retention time: 5.440 min; HRMS: m/z (M+H)⁺ =

393.1269 (Calculated for C₂₂H₂iN₂0₃S = 393.1267).

[0156] NCGC00189556 (LLI02-071_2^nd_NEG)

(S)-N-(l-(2,4-difluorophenyl)-4,5,6,7-tetrahydro-lH-indazol-4-yl)picolinamide

1H NMR (400 MHz, DMSO-^6) δ ppm 8.53 - 8.68 (m, 2 H), 8.07 - 8.13 (m, 1 H), 8.02 (td, J=7.68, 1.66 Hz, 1 H), 7.53 - 7.66 (m, 4 H), 7.23 - 7.31 (m, 1 H), 5.12 - 5.20 (m, 1 H), 2.40 - 2.58 (m, 2 H), 1.72 - 2.02 (m, 4 H); Method 1, retention time: 3.267 min; HRMS: m/z (M+H)⁺ = 355.1371 (Calculated for C^H^^O = 355.1365).

[0157] NCGC00242548 (LLI02-073)

N-(l-(4-methoxyphenyl)-4,5,6,7-tetrahydro-lH-indazol-4-yl)picolinamide

Ή NMR (400 MHz, DMSO- 6 ) δ ppm 8.60 - 8.64 (m, 1 H), 8.56 (d, J=8.22 Hz, 1 H), 8.07 - 8.12 (m, 1 H), 8.02 (td, J=7.63, 1.57 Hz, 1 H), 7.61 (ddd, J=7.53, 4.79, 1 .37 Hz, 1 H), 7.51 (s, 1 H), 7.42 - 7.49 (m, 2 H), 7.02 - 7.08 (m, 2 H), 5.1 1 - 5.19 (m, 1 H), 3.81 (s, 3 H), 2.62 - 2.79 (m, 2 H), 1.72 - 2.02 (m, 4 H); Method 1 , retention time: 5.239 min; HRMS: m/z (M+H)⁺ - 349.1667 (Calculated for C20H21N4O2 = 349.1659). [0158] NCGC00242549 (LLI02-081)

N-(l-(4-hydroxyphenyl)-4,5,6,7-tetrahydro-lH-indazol-4-yl)picolinamide

1H NMR (400 MHz, DMSO-76) δ ppm 8.62 - 8.69 (m, 2 H), 8.12 - 8.18 (m, 1 H), 8.09 (t, 7=7.63 Hz, 1 H), 7.66 (dd, J=7.04, 5.48 Hz, 1 H), 7.47 - 7.52 (m, 1 H), 7.28 - 7.36 (m, 2 H), 6.80 - 6.94 (m, 3 H), 5.10 - 5.21 (m, 1 H), 2.57 - 2.77 (m, 2 H), 1.68 - 2.05 (m, 4 H); Method 1 , retention time: 4.493 min; HRMS: m/z (M+H)⁺ = 335.1504 (Calculated for Ci₉Hi₉N₄0₂ = 335.1503).

[0159] NCGC00242550 (LLI02-085) l-(2-(3-(2-Chlorophenyl)ureido)-2-methylpropanoyl)piperidine-4-carboxylic acid

1H NMR (400 MHz, DMSO-76) 6 ppm 12.20 (s, 1 H), 8.07 (dd, J=8.22, 1.56 Hz, 1 H), 7.97 (s, 1 H), 7.47 (d, 7=16.82 Hz, 1 H), 7.39 (dd, J=8.02, 1.37 Hz, 1 H), 7.17 - 7.25 (m, 1 H), 6.90 - 6.98 (m, 1 H), 4.29 (d, 7=13.30 Hz, 2 H), 2.82 - 2.98 (m, 2 H), 2.44 (tt, 7=10.91, 4.16 Hz, 1 H), 1.76 (dd, J=13.1 1, 2.93 Hz, 2 H), 1.33 - 1.48 (m, 8 H); Method 1, retention time: 4.109 min; HRMS: m/z (M+H)⁺ 368.1372 (Calculated for Ci₇H₂₃ClN₃0₄ = 368.1372).

[0160] NCGC00242551 (LLI02-091) te -Butyl 2-(2-(2-(4-(4-(picolinamido)-4,5,6,7-tetrahydro-lH-indazol-l- yl)phenoxy)ethoxy)ethoxy)ethykarbamate

1H NMR (400 MHz, CHLOROFORM-7) 5 ppm 8.53 (ddd, J=4.79, 1.56, 0.88 Hz, 1 H), 8.26 (dt, J=7.83, 0.98 Hz, 2 H), 7.88 (td, 7=7.78, 1.66 Hz, 2 H), 7.63 (s, 1 H), 7.53 (s, 1 H), 7.40 (d, J=9.00 Hz, 2 H), 6.98 - 7.05 (m, 2 H), 5.30 - 5.41 (m, 1 H), 4.19 (dd, J=5.48, 4.1 1 Hz, 2 H), 3.90 (dd, 7=5.28, 4.1 1 Hz, 2 H), 3.71 - 3.77 (m, 2 H), 3.64 - 3.71 (m, 2 H), 3.54 - 3.61 (m, 2 H), 3.34 (ddd, 7=4.45, 2.01 , 1.17 Hz, 2 H), 2.67 - 2.76 (m, 2 H), 1.93 (br. s., 2 H), 1.22 - 1.33 (m, 9 H), 0.89 (br. s., 2 H); Method 1 , retention time: 5.694 min; HRMS: m/z (M+H)⁺ = 566.2984 (Calculated for C₃₀H₄oN₅0₆ = 566.2973).

[0161] NCGC00242552 (LLI02-098)

Ethyl l-(2-(3-(3-methoxyphenyl)ureido)-2-methylpropanoyl)piperidine-4-carboxylate

Ή NMR (400 MHz, DMSO-i/6) δ ppm 8.33 (s, 1 H), 7.06 - 7.13 (m, 2 H), 6.76 - 6.80 (m, 1 H), 6.62 (s, 1 H), 6.44 - 6.48 (m, 1 H), 4.32 (d, J=12.91 Hz, 2 H), 4.00 (q, 7=7.04 Hz, 2 H), 3.67 - 3.71 (m, 3 H), 3.21 (dt, 7=12.52, 3.91 Hz, 1 H), 2.88 (td, 7=12.13, 3.13 Hz, 2 H), 1.76 (dd, 7=12.91 , 2.74 Hz, 2 H), 1.35 - 1.48 (m, 8 H), 1.10 (t, 7=7.24 Hz, 3 H); Method 1 , retention time: 4.654 min; HRMS: m/z (M+H)⁺ = 392.2182 (Calculated for C₂oH₃₀N₃0₅ = 392.2180).

[0162] NCGC00242553 (LLI03-001)

Ethyl l-(2-(3-(3,4-difluorophenyl)ureido)-2-methylpropanoyl)piperidine-4-carboxylate

Ή NMR (400 MHz, DMSO-i½) δ ppm 8.57 (s, 1 H), 7.56 (ddd, J=13.65, 7.48, 2.54 Hz, 1 H), 7.26 (dt, J=10.61 , 9.17 Hz, 1 H), 6.97 (dddd, J=9.02, 3.99, 2.54, 1.66 Hz, 1 H), 6.75 (s, 1 H), 4.31 (dt, J=13.21 , 2.98 Hz, 2 H), 4.00 (q, J=7.1 1 Hz, 2 H), 2.77 - 3.02 (m, 2 H), 2.50 - 2.59 (m, 1 H), 1.70 - 1.82 (m, 2 H), 1.33 - 1.47 (m, 8 H), 1.10 (t, J=7.14 Hz, 3 H); Method 1, retention time: 4.934 min; HRMS: m/z (M+H)⁺ 398.1891 (Calculated for Ci₉H₂₆F₂N₃0₄ = 398.1886).

[0163] NCGC00242554 (LLI03-002)

Ethyl l-(2-(3-(2,3-dihydro-lH-inden-5-yl)ureido)-2-methyIpropanoyl)piperidine-4- carboxylate

1H NMR (400 MHz, DMSO-^6) δ ppm 8.16 (s, 1 H), 7.27 (s, 1 H), 6.95 - 7.07 (m, 2 H), 6.54 (s, 1 H), 4.32 (d, J=13.1 1 Hz, 2 H), 4.00 (q, J=7.04 Hz, 2 H), 3.25 (dt, J=12.67, 3.55 Hz, 1 H), 2.92 (td, J=12.42, 3.13 Hz, 2 H), 2.76 (ddd, J=10.42, 7.48, 7.34 Hz, 4 H), 1.97 (quin, J=7.39 Hz, 2 H), 1.72 - 1.80 (m, 2 H), 1.34 - 1.48 (m, 8 H), 1.10 (t, J=7.14 Hz, 3 H); Method 1 , retention time: 5.247 min; HRMS: m/z (M+H)⁺ = 402.2392 (Calculated for C₂₂H₃₂N₃0₄ = 402.2387).

[0164] NCGC00242555 (LLI03-003)

Ethyl l-(2-methyl-2-(3-(4-phenoxyphenyl)ureido)propanoyl)piperidine-4-carboxylate

Ή NMR (400 MHz, DMSO-c 6) δ ppm 8.35 (s, 1 H), 7.29 - 7.40 (m, 4 H), 7.03 - 7.10 (m, 1 H), 6.85 - 6.96 (m, 4 H), 6.61 (s, 1 H), 4.33 (d, J=12.91Hz, 2 H), 4.01 (q, J=7.04 Hz, 2 H), 2.82 - 2.96 (m, 2 H), 2.51 - 2.58 (m, 1 H), 1.77 (dd, J=13.1 1 , 3.33 Hz, 2 H), 1.34 - 1.50 (m, 8 H), 1.1 1 (t, J=7.24 Hz, 3 H); Method 1 , retention time: 5.531 min; HRMS: m/z (M+H)⁺ = 454.2340 (Calculated for C₂₅H₃₂N₃0₅ = 454.2336).

[0165] NCGC00242556 (LLI03-004)

Ethyl l-(2-(3-(2-chIoro-4-(trifluoromethyl)phenyl)ureido)-2- methylpropanoyl)piperidine-4-carboxylate

1H NMR (400 MHz, DMSO-d6) δ ppm 8.33 (d, J=8.80 Hz, 1 H), 8.29 (s, 1 H), 7.77 (d, J=1.57 Hz, 1 H), 7.67 (s, 1 H), 7.56 (dd, J=9.00, 1.96 Hz, 1 H), 4.18 - 4.33 (m, 2 H), 3.94 (q, J=7.04 Hz, 2 H), 2.71 - 3.02 (m, 2 H), 2.39 - 2.56 (m, 1 H), 1.73 (dd, J=13.01 , 2.64 Hz, 2 H), 1.26 - 1.44 (m, 8 H), 1.02 (t, J=7.14 Hz, 3 H); Method 1 , retention time: 5.748 min; HRMS: m/z (M+H)⁺ - = 464.1561 (Calculated for C₂₀H₂₆ClF3N₃O₄ = 464.1558).

[0166] NCGC00242559 (LLI03-008)

Ethyl l-(2-(3-(3-chloro-4-methoxyphenyl)ureido)-2-methylpropanoyl)piperidine-4- carboxylate

Ή NMR (400 MHz, DMSO-i/6) δ ppm 8.31 (s, 1 H), 7.55 (d, J=2.35 Hz, 1 H), 7.09 - 7.15 (m, 1 H), 7.01 (d, J=9.00 Hz, 1 H), 6.63 (s, 1 H), 4.32 (d, J=13.30 Hz, 2 H), 4.00 (q, J=7.04 Hz, 2 H), 3.77 (s, 3 H), 3.20 - 3.29 (m, 1 H), 2.92 (td, J=12.33, 3.13 Hz, 2 H), 1.76 (dd, J=13.1 1 , 2.93 Hz, 2 H), 1.34 - 1.48 (m, 8 H), 1.10 (t, J=7.04 Hz, 3 H); Method 1 , retention time: 4.880 min; HRMS: m/z (M+H)⁺ = 426.1792 (Calculated for C₂oH2₉ClN₃0₅ =

426.1790).

[0167] NCGC00242560 (LLI03-009)

Ethyl l-(2-(3-(2,4-dichIorophenyl)ureido)-2-methylpropanoyl)piperidine-4-carboxyIate

1H NMR (400 MHz, DMSO- 6) 5 ppm 8.11 (d, J=9.00 Hz, 1 H), 8.07 (s, 1 H), 7.55 (d, J=2.35 Hz, 1 H), 7.50 (s, 1 H), 7.30 (dd, J=9.00, 2.74 Hz, 1 H), 4.29 (d, J=13.30 Hz, 2 H), 3.99 (q, J=7.04 Hz, 2 H), 2.84 - 2.97 (m, 2 H), 2.51 - 2.57 (m, 1 H), 1.76 (dd, J=13.30, 3.13 Hz, 2 H), 1.32 - 1.45 (m, 8 H), 1.09 (t, J=7.04 Hz, 3 H); Method 1 , retention time: 5.494 min; HRMS: m/z (M+H)⁺ 430.1297 (Calculated for Ci₉H₂₆Cl₂N₃0₄ = 430.1295).

[0168] NCGC00242565 (LLI03-019)

Ethyl l-(2-(3-(4-cyanophenyl)ureido)-2-niethylpropanoyI)piperidine-4-carboxylate

Ή NMR (400 MHz, DMSO- 6) δ ppm 8.89 (s, 1 H), 7.65 (d, J=9.00 Hz, 2 H), 7.51 (d, J=9.00 Hz, 2 H), 6.90 (s, 1 H), 4.30 (d, J=13.30 Hz, 2 H), 3.99 (q, J=7.17 Hz, 2 H), 2.79 - 2.99 (m, 2 H), 2.51 - 2.59 (m, 1 H), 1.76 (dd, J=12.91 , 2.74 Hz, 2 H), 1.30 - 1.48 (m, 8 H), 1.09 (t, J=7.24 Hz, 3 H); Method 1 , retention time: 4.569 min; HRMS: m/z (M+H)⁺ = 387.2028 (Calculated for C₂₀H₂₇N₄O₄ = 387.2027).

[0169] NCGC00242566 (LLI03-021)

Ethyl l-(2-methyl-2-(3-naphthalen-2-ylureido)propanoyl)piperidine-4-carboxylate

Ή NMR (400 MHz, DMSO-c 6) δ ppm 8.55 (s, 1 H), 7.99 (d, J=l .96 Hz, 1 H), 7.69 - 7.79 (m, 3 H), 7.35 - 7.44 (m, 2 H), 7.28 - 7.34 (m, 1 H), 6.73 (s, 1 H), 4.35 (d, J=13.30 Hz, 2 H), 3.94 (q, J=7.04 Hz, 2 H), 2.83 - 3.00 (m, 2 H), 2.52 - 2.58 (m, 1 H), 1.72 - 1.83 (m, 2 H), 1.38 - 1.51 (m, 8 H), 1.02 (t, J=7.04 Hz, 3 H); Method 1 , retention time: 5.223 min; HRMS: m/z (M+H)⁺ = 412.2235 (Calculated for C₂3H3oN₃0₄ = 412.2231).

[0170] NCGC00242567 (LLI03-022)

Ethyl l-(2-(3-benzo[b]thiophen-5-ylureido)-2-methylpropanoyl)piperidine-4- carboxylate

Ή NMR (400 MHz, DMSO-c 6) δ ppm 8.41 (s, 1 H), 7.99 (d, J=1.96 Hz, 1 H), 7.80 (d, J=8.61 Hz, 1 H), 7.68 (d, J=5.09 Hz, 1 H), 7.32 (d, J=5.48 Hz, 1 H), 7.23 (dd, J=8.61, 1.96 Hz, 1 H), 6.65 (s, 1 H), 4.34 (d, J=13.30 Hz, 2 H), 3.96 (q, J=7.17 Hz, 2 H), 2.80 - 3.01 (m, 2 H), 2.51 - 2.58 (m, 1 H), 1.77 (dd, J=13.1 1 , 2.93 Hz, 2 H), 1.37 - 1.51 (m, 8 H), 1.05 (t, J=7.04 Hz, 3 H); Method 1, retention time: 5.078 min; HRMS: m/z (M+H)⁺ = 418.1800 (Calculated for C^gNaC^S = 418.1795).

[0171] NCGC00242568 (LLI03-023)

Ethyl l-(2-(3-biphenyl-4-ylureido)-2-methylpropanoyl)piperidine-4-carboxylate

1H NMR (400 MHz, DMSO-c/6) δ ppm 8.44 (s, 1 H), 7.60 (dd, J=8.41 , 1.37 Hz, 2 H), 7.50 - 7.55 (m, 2 H), 7.38 - 7.47 (m, 4 H), 7.26 - 7.32 (m, 1 H), 6.67 (s, 1 H), 4.34 (d, J=13.30 Hz, 2 H), 3.99 (q, J=7.30 Hz, 2 H), 2.81 - 3.01 (m, 2 H), 2.51 - 2.58 (m, 1 H), 1.77 (dd, J=12.91 , 2.74 Hz, 2 H), 1.35 - 1.50 (m, 8 H), 1.08 (t, J=7.04 Hz, 3 H); Method 1, retention time: 5.538 min; HRMS: m/z (M+H)⁺ = 438.2395 (Calculated for C₂₅H₃iN₃0₄ = 438.2387).

[0172] NCGC00242571 (LLI03-036)

N-(l-(2-hydroxyethyl)-4,5,6,7-tetrahydro-lH-indazol-4-yl)picolinamide

Ή NMR (400 MHz, CHLOROFORM-d) δ ppm 8.51 (ddd, J=4.84, 1.71 , 0.88 Hz, 1 H), 8.24 (dt, J=7.83, 1.08 Hz, 1 H), 8.17 (d, J=7.43 Hz, 1 H), 7.87 (td, J=7.73, 1.76 Hz, 1 H), 7.48 (s, 1 H), 7.43 (ddd, J=7.58, 4.84, 1.27 Hz, 1 H), 5.23 - 5.30 (m, 1 H), 4.09 - 4.15 (m, 1 H), 3.99 - 4.05 (m, 2 H), 2.56 - 2.73 (m, 2 H), 2.06 - 2.15 (m, 2 H), 1.82 - 2.06 (m, 4 H); Method 1 , retention time: 3.516 min; HRMS: m/z (M+H)⁺ = 287.1503 (Calculated for Ci₅Hi₉N₄0₂ = 287.1503).

[0173] NCGC00242572 (LLI03-037) tert-Butyl 2-(2-(2-(2-(4-(picolinamido)-4,5,6,7-tetrahydro-lH-indazoI-l- yl)ethoxy)ethoxy)ethoxy)ethylcarbamate

Ή NMR (400 MHz, CHLOROFORM-<f) δ ppm 8.44 - 8.58 (m, 1 H), 8.24 (d, J=7.83 Hz, 1 H), 8.16 (d, J=8.02 Hz, 1 H), 7.86 (td, J=7.73, 1 .17 Hz, 1 H), 7.36 - 7.53 (m, 2 H), 5.20 - 5.29 (m, 1 H), 5.04 - 5.13 (m, 1 H), 4.16 - 4.25 (m, 2 H), 3.80 - 3.89 (m, 2 H), 3.50 - 3.63 (m, 8 H), 3.27 - 3.36 (m, 2 H), 2.62 - 2.75 (m, 2 H), 2.04 - 2.15 (m, 2 H), 1.78 - 2.03 (m, 4 H), 1.38

- 1.50 (m, 9 H); Method 1 , retention time: 4.956 min; HRMS: m/z (M+H)⁺ = 518.2978 (Calculated for C26H40N5O6 = 518.2973).

[0174] NCGC00242573 (LLI03-044)

N-(l-(3-methoxyphenyl)-4,5,6,7-tetrahydro-lH-indazol-4-yl)picolinamide

1H NMR (400 MHz, DMSO- 6) δ ppm 8.60 - 8.63 (m, 1 H), 8.59 (d, J=8.22 Hz, 1 H), 8.08 - 8.12 (m, 1 H), 8.00 - 8.05 (m, 1 H), 7.61 (ddd, J=7.53, 4.79, 1.37 Hz, 1 H), 7.56 (s, 1 H), 7.41 (t, J=8.22 Hz, 1 H), 7.09 - 7.15 (m, 2 H), 6.93 - 6.98 (m, 1 H), 5.12 - 5.19 (m, 1 H), 3.81 (s, 3 H), 2.79 (dt, J=l 1.84, 6.02 Hz, 2 H), 1.77 - 2.01 (m, 4 H); Method 1, retention time: 5.454 min; HRMS: m/z (M+H)⁺ = 349.1662 (Calculated for C₂₀H₂iN₄O₂ = 349.1659).

[0175] NCGC00242574 (LLI03-047)

N-(l-(3-hydroxyphenyI)-4,5,6,7-tetrahydro-lH-indazol-4-yl)picolinamide

1H NMR (400 MHz, DMSO- 6) δ ppm 9.77 (br. s., 1 H), 8.53 - 8.67 (m, 2 H), 8.07 - 8.14 (m,

1 H), 8.02 (td, J=7.68, 1.66 Hz, 1 H), 7.61 (ddd, J=7.58, 4.74, 1.37 Hz, 1 H), 7.53 (s, 1 H), 7.28 (t, J=8.31 Hz, 1 H), 6.93 - 7.01 (m, 2 H), 6.76 (ddd, J=8.22, 2.35, 0.98 Hz, 1 H), 5.09 - 5.20 (m, 1 H), 2.68 - 2.86 (m, 2 H), 1.71 - 2.04 (m, 4 H); Method 1, retention time: 4.686 min; HRMS: m/z (M+H)⁺ = 335.1506 (Calculated for Ci₉Hi₉N₄0₂ = 335.1503).

[0176] NCGC00242575 (LLI03-050) tert-Butyl 2-(2-(2-(3-(4-(picolinamido)-4,5,6,7-tetrahydro-lH-indazol-l- yl)phenoxy)ethoxy)ethoxy)ethylcarbamate

Ή NMR (400 MHz, DMSO-J6) δ ppm 8.53 - 8.66 (m, 2 H), 8.07 - 8.14 (m, 1 H), 7.97 - 8.07 (m, 1 H), 7.61 (ddd, J=7.53, 4.79, 1.37 Hz, 1 H), 7.55 (s, 1 H), 7.40 (t, J=8.22 Hz, 1 H), 7.07

- 7.18 (m, 2 H), 6.93 - 6.99 (m, 1 H), 6.71 - 6.78 (m, 1 H), 5.09 - 5.21 (m, 1 H), 4.1 1 - 4.19 (m, 2 H), 3.72 - 3.82 (m, 2 H), 3.56 - 3.62 (m, 2 H), 3.49 - 3.56 (m, 2 H), 3.06 (q, J=5.93 Hz,

2 H), 2.80 (dd, J=l 1.84, 6.55 Hz, 2 H), 1.97 (ddd, J=3.42, 2.45, 0.78 Hz, 6 H), 1.36 (s, 9 H); Method 1 , retention time: 5.902 min; HRMS: m/z (M+H)⁺ = 566.2979 (Calculated for C₃oH₄oN₅0₆ = 566.2973).

[0177] NCGC00242563 (LLI03-065) l-(2-(3-(2-Chlorophenyl)ureido)-2-methylpropanoyl)-N-ethylpiperidine-4-carboxamide

Ή NMR (400 MHz, DMSO-i 6) δ ppm 8.09 (dd, J=8.22, 1.57 Hz, 1 H), 7.95 (s, 1 H), 7.69 (t, 7=5.48 Hz, 1 H), 7.44 (s, 1 H), 7.39 (dd, 7=8.02, 1.37 Hz, 1 H), 7.18 - 7.25 (m, 1 H), 6.94 (td, J=7.63, 1.57 Hz, 1 H), 4.40 (d, J=13.30 Hz, 2 H), 2.96 - 3.05 (m, 2 H), 2.69 - 2.84 (m, 2 H), 2.20 - 2.30 (m, J=l 1.25, 11.25, 3.91 , 3.72 Hz, 1 H), 1.63 (dd, 7=12.52, 2.35 Hz, 2 H), 1.34 - 1.48 (m, 8 H), 0.95 (t, J=7.24 Hz, 3 H); Method 1 , retention time: 4.206 min; HRMS: m/z (M+H)⁺ = 395.1837 (Calculated for Ci₉H₂₈ClN₄0₃ = 395.1844).

[0178] NCGC00242564 (LLI03-066) l-(2-(3-(2-Chlorophenyl)ureido)-2-methylpropanoyl)-N,N-diethylpiperidine-4- carboxamide

Ή NMR (400 MHz, DMSO-c/6) δ ppm 8.10 (dd, J=8.41 , 1.37 Hz, 1 H), 7.95 (s, 1 H), 7.45 (s, 1 H), 7.38 (dd, J=8.02, 1.37 Hz, 1 H), 7.22 (ddd, J=8.41 , 7.24, 1.57 Hz, 1 H), 6.91 - 6.97 (m, 1 H), 4.44 (d, J=12.91 Hz, 2 H), 3.26 - 3.38 (m, 2 H), 3.20 (q, J=7.04 Hz, 2 H), 2.76 - 3.02 (m, 2 H), 2.65 - 2.76 (m, 1 H), 1.33 - 1.64 (m, 10 H), 1.09 (t, J=7.04 Hz, 3 H), 0.95 (t, J=7.04 Hz, 3 H); Method 1 , retention time: 4.810 min; HRMS: m/z (M+H)⁺ = 423.2158 (Calculated for C₂iH₃₂ClN₄0₃ = 423.2157).

[0179] NCGC00244462 (LLI03-089)

N-(l-(4-(2-(2-(2-(5-((3aS,4S,6aR)-2-oxohexahydro-lH-thieno[3,4-d]imidazol-4- yl)pentanamido)ethoxy)ethoxy)ethoxy)phenyl)-4,5,6,7-tetrahydro-lH-indazol-4- yl)picolinamide

Ή NMR (400 MHz, DMSO-76) 6 ppm 8.57 - 8.63 (m, 1 H), 8.53 (d, J=8.22 Hz, 1 H), 8.04 - 8.1 1 (m, 1 H), 7.99 (td, J=7.63, 1.57 Hz, 1 H), 7.79 (t, J=5.67 Hz, 1 H), 7.58 (ddd, J=7.53, 4.79, 1.37 Hz, 1 H), 7.48 (s, 1 H), 7.39 - 7.45 (m, 2 H), 6.99 - 7.08 (m, 2 H), 6.37 (br. s., 1 H), 5.07 - 5.17 (m, 2 H), 4.26 (dd, J=7.63, 4.50 Hz, 1 H), 4.04 - 4.15 (m, 3 H), 3.74 (dd, J=5.48, 3.91 Hz, 2 H), 3.54 - 3.63 (m, 2 H), 3.38 (t, 7=5.87 Hz, 2 H), 3.12 - 3.21 (m, 2 H), 3.05 (ddd, 7=8.41 , 6.26, 4.50 Hz, 1 H), 2.78 (dd, 7=12.33, 5.28 Hz, 1 H), 2.60 - 2.72 (m, 2 H), 2.54 (d, J=12.52 Hz, 1 H), 2.03 (t, J=7.43 Hz, 2 H), 1.70 - 1.99 (m, 4 H), 1.35 - 1.64 (m, 5 H), 1.16 - 1.34 (m, 3 H); Method 1 , retention time: 4.669 min; HRMS: m/z (M+H)⁺ = = 692.3235 (Calculated for C₃₅H₄₆N₇0₆S = 692.3225).

[0180] NCGC00244960 (LLI04-001)

(S)-ethyl l-(3-(benzyloxy)-2-(3-(2-chlorophenyl)ureido)propanoyl)piperidine-4- carboxylate Ή NMR (400 MHz, DMSO-i 6) δ ppm 8.37 (d, J=8.22 Hz, 1 H), 8.08 (td, J-8.41 , 1.57 Hz, 1 H), 7.54 (d, J=8.61 Hz, 1 H), 7.19 - 7.42 (m, 7 H), 6.96 (td, J=7.63, 1.57 Hz, 1 H), 4.95 (dt, J=8.22, 5.87 Hz, 1 H), 4.44 - 4.57 (m, 2 H), 4.25 (t, J=12.52 Hz, 1 H), 4.06 (q, J=7.04 Hz, 2 H), 3.88 -

3.99 (m, 1 H), 3.56 (d, J=5.48 Hz, 2 H), 3.07 - 3.20 (m, 1 H), 2.72 - 2.86 (m, 1 H), 2.59 (br. s., 1 H), 1.75 - 1.89 (m, 2 H), 1.32 - 1.45 (m, 2 H), 1.17 (t, J=7.04 Hz, 3 H); Method 1, retention time: 6.137 min; HRMS: m/z (M+H)⁺ = 488.1954 (Calculated for C₂₅H₃₁C1N₃0₅ = 488.1947).

[0181] NCGC00244961 (LLI04-002)

(R)-ethyl l-(3-(benzyloxy)-2-(3-(2-chlorophenyl)ureido)propanoyl)piperidine-4- carboxylate

1H NMR (400 MHz, DMSO- 6) δ ppm 8.37 (d, J=8.22 Hz, 1 H), 8.04 - 8.13 (m, 1 H), 7.54 (d, J=8.22 Hz, 1 H), 7.18 - 7.42 (m, 7 H), 6.96 (td, J=7.63, 1.57 Hz, 1 H), 4.95 (ddd, J=8.41, 5.87, 5.67 Hz, 1 H), 4.44 - 4.57 (m, 2 H), 4.25 (t, J=13.30 Hz, 1 H), 4.06 (q, J=7.04 Hz, 2 H), 3.87 - 3.99 (m, 1 H), 3.56 (d, J=5.48 Hz, 2 H), 3.05 - 3.21 (m, 1 H), 2.72 - 2.86 (m, 1 H), 2.53

- 2.64 (m, 1 H), 1.75 - 1.89 (m, 2 H), 1.32 - 1.45 (m, 2 H), 1.17 (t, J=7.04 Hz, 3 H); Method 1 , retention time: 6.145 min; HRMS: m/z (M+H)⁺ = 488.1952 (Calculated for

= 488.1947).

[0182] NCGC00244965 (LLI04-051)

N-(l-(4-(2-(2-(2-(5-(l-(7-hydroxy-2-oxo-2H-chromen-3-yl)-lH-l,2,3-triazol-4- yl)pentanamido)ethoxy)ethoxy)ethoxy)phenyl)-4,5,6,7-tetrahydro-lH-indazoI-4- yl)picolinamide

Ή NMR (400 MHz, CHLOROFORM-d) δ ppm 8.54 (d, J=3.72 Hz, 1 H), 8.35 (s, 1 H), 8.22

- 8.32 (m, 2 H), 7.84 - 7.95 (m, 1 H), 7.67 (br. s., 1 H), 7.41 - 7.49 (m, 1 H), 7.34 (d, J=8.61 Hz, 2 H), 6.92 (d, J=8.02 Hz, 2 H), 6.75 (d, J=8.22 Hz, 1 H), 6.58 (br. s., 1 H), 6.29 (br. s., 1 H), 5.31 - 5.40 (m, 1 H), 4.04 - 4.16 (m, 2 H), 3.83 (td, J=3.72, 0.98 Hz, 2 H), 3.66 (ddd, J=15.1 1 , 3.77, 1.86 Hz, 4 H), 3.54 - 3.61 (m, 2 H), 3.42 - 3.53 (m, 2 H), 2.79 - 2.88 (m, 3 H), 2.61 - 2.75 (m, 3 H), 2.26 (ddd, J=7.04, 4.89, 2.54 Hz, 2 H), 2.13 - 2.22 (m, 1 H), 1.87 - 2.05 (m, 4 H), 1.65 - 1.83 (m, 4 H); Method 1 , retention time: 5.171 min; HRMS: m/z (M+H)⁺ = 777.3368 (Calculated for C₄iH₄5N₈0₈ = 777.3355).

[0183] NCGC00244966 (LLI04-052) N-(l-(4-(2-(2-(2-(2-(l-(7-hydroxy-2-oxo-2H-chromen-3-yl)-lH-l,2,3-triazol-4- yl)ethylamino)ethoxy)ethoxy)ethoxy)phenyl)-4,5,6,7-tetrahydro-lH-indazol-4- yl)picolinamide

Ή NMR (400 MHz, DMSO- 6) 5 ppm 10.94 (s, 1 H), 8.59 - 8.69 (m, 3 H), 8.57 (s, 1 H), 8.55 (d, J=8.22 Hz, 1 H), 8.49 (s, 1 H), 8.07 - 8.13 (m, 1 H), 7.99 - 8.06 (m, 1 H), 7.75 (d,

J=8.61 Hz, 1 H), 7.61 (ddd, J=7.53, 4.79, 1.37 Hz, 1 H), 7.50 (s, 1 H), 7.41 - 7.46 (m, 2 H), 7.02 - 7.08 (m, 2 H), 6.91 (dd, J=8.61 , 2.35 Hz, 1 H), 6.85 (d, J=2.35 Hz, 1 H), 5.10 - 5.19 (m, 1 H), 4.15 (dd, J=5.48, 3.52 Hz, 2 H), 3.76 - 3.81 (m, 2 H), 3.69 - 3.74 (m, 2 H), 3.61 - 3.69 (m, 4 H), 3.18 - 3.26 (m, 2 H), 3.08 - 3.15 (m, 2 H), 2.65 - 2.72 (m, 2 H), 1.73 - 2.00 (m, 5 H); Method 1 , retention time: 4.328 min; HRMS: m/z (M+H)⁺ = 721.3097 (Calculated for C₃8H4iN₈0₇ = 721.3093).

EXAMPLE 10

[0184] This example provides S3 lipid droplet data, S3 cytotoxicity data, and Cos-7 lipid droplet data exhibited by various embodiments of the invention. The results are set forth in Table 4.

Table 4

Compounds of Formula I

S3 Lipid Droplet Data S3 Cytotox Data Cos-7

Lipid Droplet Data

Sample ID AC50(uM) Max Resp AC50(uM) Efficacy A(absent),

R (reduced) NE (no effect)

NCGC00189332- 01 0.056 -100.7321 12.5385 -99.6724 A

NCGC00189555- 01 0.0397 -102.6354 12.5385 -91 .4422 R

NCGC00189556- 01 12.5385 -20.451 1 >57 <-10 R

NCGC00189556- 02 7.91 12 -73.2064 >57 <-10 R

NCGC00238536- 01 15.785 -78.6466 3.5338 -81.9468 NE

NCGC00238537- 01 0.3534 -105.4173 15.785 -101 .2671 A

NCGC00238537- 02 0.315 -105.8565 4.9917 -99.5507 A

NCGC00238539- 01 0.1254 -106.4422 4.4488 -56.1755 A NCGC00238541 - 01 3.5338 -103.9098 15.785 -83.7849 A

NCGC00238543- 01 0.8877 -20.6015 >57 <-10 NE

NCGC00238544- 01 null 5.2709 >57 <-10 NE

NCGC00238547- 01 7.91 12 -87.5549 28.0702 -47.9862 NE

NCGC00238548- 01 0.1 1 17 -102.9283 8.8766 -98.6927 R

NCGC00238548- 02 0.1 1 17 -105.2709 15.785 -94.6374 NE

NCGC00238552- 01 15.785 -88.7262 1 .771 1 -101 .0774 NE

NCGC00238553- 01 14.0684 -70.8638 14.0684 -54.0436 NE

NCGC00238555- 01 null -4.9624 >57 <-10 NE

NCGC00238556- 01 28.0702 -78.6237 2.807 -114.0633 NE

NCGC00238557- 01 null -2.2556 8.8766 -58.1773 NE

NCGC00238558- 01 1.2538 -7.1742 >57 <-10 NE

NCGC00238559- 01 0.1407 -105.4135 4.4488 -97.4066 NE

NCGC00238560- 01 null -6.1654 >57 <-10 NE

NCGC00238561 - 01 7.91 12 -94.4361 17.7111 -44.5996 NE

NCGC00241451 - 01 8.8766 -43.1918 2.2297 -88.4556 NE

NCGC00242548- 01 0.0071 -85.8647 7.0509 -57.5347 NE

NCGC00242549- 01 0.01 -89.6241 17.71 1 1 -52.6097 A

NCGC00242551 - 01 0.0158 -105.2632 2.807 -78.1073 R

NCGC00242571 - 01 14.0684 -78.7701 >57 <-10 R

NCGC00242572- 01 2.2297 -90.6767 25.0176 -43.1033 NE

NCGC00242573- 01 0.0223 -90.2256 14.0684 -65.173 A

NCGC00242574- 01 0.1987 -95.754 19.8722 -57.2459 A

NCGC00242575- 01 0.0705 -106.7669 8.8766 -113.7967 A

NCGC00244462- 01 0.0158 -99.1792 15.785 -64.0914 A

NCGC00244959- 01 null -1 .6997 NE

NCGC00244962- 01 0.0353 -100.4249 17.71 1 1 -60.5182 A

NCGC00244963- 01 15.785 -102.4079 14.0684 -105.8624 NE

NCGC00244964- 01 0.01 -104.104 6.2841 -85.9431 A NCGC00244964- 02 0.01 12 -103.1464 12.5385 -88.279 A

NCGC00244965- 01 0.0397 -93.7073 5.6007 -54.5414 A

NCGC00244966- 01 0.0223 -102.1888 17.7111 -43.6337 A

Compounds of Formula II

S3 Lipid Droplet Data S3 Cytotox Data Cos-7

Lipid Droplet Data

Sample ID AC50(uM) Max Resp AC50(uM) Efficacy A(absent),

R (reduced) NE (no effect)

NCGC00092589- 02 3.965 -73.985 19.8722 -49.2477 A

NCGC001 12165- 02 2.2297 -84.3338 14.0684 -60.8977 A

NCGC00238538- 01 12.5385 -12.6316 >57 <-10 A

NCGC00238540- 01 4.4488 -20.937 >57 <-10 N

NCGC00238546- 01 0.996 -14.2857 17.71 1 1 -53.4788 A

NCGC00238550- 01 1 .1175 -95.754 15.785 -48.7975 A

NCGC00238551 - 01 0.3534 -92.6316 1.9872 -41 .3596 A

NCGC00241413- 01 0.5601 -4.0996 >57 <-10 NE

NCGC00241414- 01 0.7911 -3.8067 >57 <-10 NE

NCGC00241415- 01 0.0008 -9.1729 25.0176 -63.7714 NE

NCGC00241416- 01 0.0353 1.4641 >57 <-10 NE

NCGC00241417- 01 15.785 -67.3684 12.5385 -65.1251 R

NCGC00241418- 01 null -10.0752 17.71 1 1 -50.9293 NE

NCGC00241419- 01 null -3.6603 15.785 -45.5682 NE

NCGC00241420- 01 0.0353 -5.4173 >57 <-10 NE

NCGC00241421 - 01 null -21 .4774 >57 <-10 NE

NCGC00241422- 01 null -22.406 12.5385 -98.8098 NE

NCGC00241423- 01 7.0509 -38.9474 14.0684 -60.1967 R

NCGC00241424- 01 0.7051 -94.1435 28.0702 -54.8531 A

NCGC00241425- 4.4488 -100.4392 25.0176 -45.2889 A 01

NCGC00241426- 01 0.0499 -103.8067 12.5385 -51 .7837 A

NCGC00241427- 01 0.8877 -98.5359 9.9597 -55.091 A

NCGC00241428- 01 0.0628 -100.9023 17.7111 -76.1192 A

NCGC00241429- 01 0.0397 -100.6015 25.0176 -77.1368 A

NCGC00241430- 01 1 .771 1 -87.1157 7.91 12 -62.5658 A

NCGC00241431 - 01 0.2807 -100.4511 15.785 -69.319 A

NCGC00241432- 01 2.2297 -18.448 17.711 1 -37.1109 NE

NCGC00241433- 01 14.0684 -47.6692 17.7111 -40.2916 NE

NCGC00241434- 01 4.4488 -55.188 22.2969 -46.8931 R

NCGC00241435- 01 0.0044 9.3704 15.785 -63.551 NE

NCGC00241436- 01 12.5385 -46.5593 12.5385 -51 .6288 NE

NCGC00241437- 01 null -9.3704 15.785 -44.2225 NE

NCGC00241438- 01 1 .4068 -9.0776 14.0684 -87.4296 NE

NCGC00241439- 01 null 1.6541 15.785 -42.3881 NE

NCGC00241440- 01 31 .5573 -98.7252 12.5632 -57.0247 NE

NCGC00241441 - 01 5.6007 -85.798 15.785 -66.3891 NE

NCGC00241442- 01 0.044 10.2489 13.9119 -32.6435 NE

NCGC00241443- 01 1 1.1749 -16.8421 17.71 1 1 -43.024 NE

NCGC00241444- 01 1.2806 -16.2406 9.0657 -41 .299 NE

NCGC00241445- 01 17.7111 -36.0902 15.785 -53.0237 NE

NCGC00241452- 01 15.785 -82.4897 12.5385 -61 .0015 NE

NCGC00241453- 01 null -13.6842 14.0684 -54.7667 R

Compounds of Formula III

S3 Lipid Droplet Data S3 Cytotox Data Cos-7

Lipid Droplet Data

Sample ID AC50(uM) Max Resp AC50(uM) Efficacy A(absent),

R (reduced) NE (no effect) NCGC00034917- 5.6007 -93.9971 >57 <-10 A 03

NCGC00238542- 15.785 -87.1 157 >57 <-10 A 01

NCGC00241446- 14.0684 -37.594 >57 <-10 R 01

NCGC00241447- 7.91 12 -92.6316 >57 <-10 R 01

NCGC00241448- 4.9917 -90.4832 >57 <-10 R 01

NCGC00241449- 1.1 175 -4.246 >57 <-10 NE 01

NCGC00241450- 4.9917 -96.9253 >57 <-10 R 01

NCGC00242550- 0.996 -5.4173 >57 <-10 NE 01

NCGC00242552- 17.7111 -57.594 17.71 1 1 -30.8915 R 01

NCGC00242553- 28.0702 -52.2694 >57 <-10 R 01

NCGC00242554- null -27.9649 >57 <-10 NE 01

NCGC00242555- 1 1 .1749 -100.5857 15.785 -47.3675 A 01

NCGC00242556- 1.1 175 -101.1713 17.71 11 -56.1647 A 01

NCGC00242557- 0.0158 -1.4641 >57 <-10 NE 01

NCGC00242558- 7.0509 -17.4231 >57 <-10 NE 01

NCGC00242559- 22.2969 -13.9092 >57 <-10 NE 01

NCGC00242560- 2.5018 -96.7789 22.2969 -27.6693 A 01

NCGC00242561 - null -19.9122 >57 <-10 NE 01

NCGC00242562- 0.0071 - 1.2782 >57 <-10 NE 01

NCGC00242563- 25.0176 -39.8496 >57 <-10 NE 01

NCGC00242563- 17.7111 -59.9179 >57 <-10 NE 02

NCGC00242564- 25.0176 -44.812 >57 <-10 NE 01

NCGC00242564- 17.71 1 1 -67.8523 >57 <-10 A 02

NCGC00242565- 1.1 1 75 -19.6992 >57 <-10 NE 01

NCGC00242566- null -41 .6541 >57 <-10 NE 01

NCGC00242567- 12.5385 -27.3684 >57 <-10 NE 01

NCGC00242568- 8.8766 -87.2621 28.0702 -49.9275 A 01

NCGC00242569- 9.9597 -15.8126 >57 <-10 NE 01

NCGC00242570- 0.0071 -1 1 .1274 >57 <-10 NE 01

NCGC00244960- 12.5385 -1 1 .6147 >57 <-10 NE 01

NCGC00244961 - 31 .4952 -48.8372 >57 <-10 NE 01

EXAMPLE 1 1

[0185] This example demonstrates a synthesis of an exemplary embodiment of a compound of Formula I of the invention.

[0186] The synthesis is depicted in Scheme 4.

S

[0187] Scheme 4, Step 1. To a solution of 6,7-dihydro-lH-indazol-4(5H)-one (0.1 g, 0.734 mmol) in DCM (3.5 ml) were added DMAP (0.108 g, 0.881 mmol) and BOC₂0 (0.232 ml, 0.999 mmol). The mixture was stirred at r.t. for lh. Evaporation of the solvent and purification by Biotage, eluting with a hexanes-EtOAc gradient, gave title product (0.16g, 92%).

[0188] Scheme 4, Step 2. To a solution of tert-butyl 4-oxo-4,5,6,7-tetrahydro-lH- indazole-l -carboxylate (3.04 g, 12.87 mmol) in iPrOH (120 ml) was added ammonium acetate (9.92 g, 129 mmol) and stirred at r.t. for 2 hrs. To the reaction mixture were added 4A molecule sieves (powder) and sodium cyanoborohydride (4.04 g, 64.3 mmol). The mixture was stirred at 70°C for 2 hrs and filtered. The solvent was removed. The residue was diluted with EtOAc and washed with IN NaOH and brine. The organic layer was dried over Na₂S0₄ and concentrated. The crude product was used in the next reaction without purification.

[0189] Scheme 4, Step 3. To a solution of picolinic acid (1.226 g, 9.96 mmol) and

HATU (4.17 g, 10.96 mmol) in DMF (85 ml) was added DIPEA (5.22 ml, 29.9 mmol). The mixture was stirred at r.t. for 10 min. tert-butyl 4-amino-4,5,6,7-tetrahydro-lH-indazole-l- carboxylate (2.6 g, 10.96 mmol) was added to the mixture. The reaction mixture was stirred at r.t. for 2 hrs. Water (160 ml) was added to the mixture. The solid was filtered and washed with water, and dried. The crude product was purified by Biotage, eluting with a hexanes- EtOAc gradient, to give title product (1.8 g, 53%).

[0190] Scheme 4, Step 4. To the solution of tert-butyl 4-(picolinamido)-4,5,6,7- tetrahydro-lH-indazole-l-carboxylate (1.8 g, 5.26 mmol) in DCM (50 ml) was added TFA (5 mL, 64.9 mmol). The mixture was stirred at r.t. for overngiht. The solvent was removed. The crude product was used in next reaction without purification.

[0191] Scheme 4, Step 5. The mixture of N-(4,5,6,7-tetrahydro-lH-indazol-4- yl)picolinamide (50 mg„ 2-fluoropyridine and NaH in DMF (1 ml) was irradiated in a microwave reactor for 30 min at 120 °C. Water was added to the mixture, and then purified by reverse phase purification system to give the title product as a TFA salt.

[0192] Ή NMR (400 MHz, DMSO- 6) δ ppm 8.75 (d, J=7.83 Hz, 1 H), 8.63 (dq,

J=4.74, 0.90 Hz, 1 H), 8.37 - 8.40 (m, 1 H), 8.36 (s, 1 H), 8.09 - 8.13 (m, 1 H), 8.02 (td, J=7.73, 1.76 Hz, 1 H), 7.91 - 7.97 (m, 1 H), 7.82 - 7.87 (m, 1 H), 7.61 (ddd, J=7.43, 4.70, 1.17 Hz, 1 H), 7.28 (ddd, J=7.34, 4.99, 0.98 Hz, 1 H), 5.14 (td, J=7.73, 4.89 Hz, 1 H), 2.67 - 2.73 (m, 2 H), 2.00 - 2.07 (m, 2 H), 1.76 - 1.92 (m, 2 H); Method 1 , retention time: 5.153 min; HRMS: m/z (M+H)⁺ = 320.1496 (Calculated for Ci₈H₁₈N₅0 = 320.1506).

EXAMPLE 12

[00104] This example demonstrates a synthesis of an exemplary embodiment of a compound of Formula I of the invention.

[00105] The synthesis is depicted in Scheme 5.

Scheme 5

[0193] Scheme 5, Step 1. To a soultion of N-(4,5,6,7-tetrahydro-lH-indazol-4- yl)picolinamide (50 mg, 0.206 mmol) in DMF (1 ml) was added potassium carbonate (86 mg, 0.619 mmol). The mixture was stirred at r.t. for 10 min. To this mixture was added 1- (bromomethyl)-2,4-difluorobenzene (51.3 mg, 0.248 mmol). The mixture was stirred at 80 °C for 2 days. Water was added to the mixture, and then purified by reverse phase purification system to give the title product as a TFA salt.

[0194] 1H NMR (400 MHz, DMSO- 6) δ ppm 8.61 (dq, J=4.74, 0.90 Hz, 1 H), 8.53 (d, J=8.61 Hz, 1 H), 8.05 - 8.11 (m, 1 H), 7.97 - 8.05 (m, 1 H), 7.57 - 7.64 (m, 2 H), 7.32 (td, J=8.71 , 6.85 Hz, 1 H), 7.24 (ddd, J=10.37, 9.39, 2.54 Hz, 1 H), 7.02 - 7.10 (m, 1 H), 5.23 (s, 2 H), 5.06 (td, J=7.73, 4.89 Hz, 1 H), 2.53 (dd, J=6.65, 1.96 Hz, 2 H), 1.87 - 1.99 (m, 2 H), 1.66 - 1.83 (m, 2 H); Method 1, retention time: 5.345 min; HRMS: m/z (M+H)⁺ = 369.1515 (Calculated for C₂oHi9F₂N₄0 = 369.1521).

EXAMPLE 13

[00106] This example demonstrates a synthesis of an exemplary embodiment of a compound of the invention.

[00107] The synthesis is depicted in Scheme 6.

Scheme 6

[0195] Scheme 6, Step 1. The title product was prepared according to the method used to prepare compound described in Scheme 4, Step 3 above, substituting 2-((tert- butoxycarbonyl)amino)-2-methylpropanoic acid for picolinic acid and substituting ethyl piperidine-4-carboxylate for tert-butyl 4-amino-4,5,6,7-tetrahydro-lH-indazole-l- carboxylate.

[0196] Scheme 6, Step 2. The title product was prepared according to the method used to prepare compound described inScheme 4, Step 4 above, substituting ethyl l-(2-((tert- butoxycarbonyl)amino)-2-methylpropanoyl)piperidine-4-carboxylate for tert-butyl 4- (picolinamido)-4,5,6,7-tetrahydro-lH-indazole-l-carboxylate.

[0197] Scheme 6, Step 3. The title product was prepared according to the method used to prepare compound described inScheme 4, Step 3 above, substituting 2-chlorobenzoic acid for picolinic acid and substituting ethyl l-(2-amino-2-methylpropanoyl)piperidine-4- carboxylate for tert-butyl 4-amino-4,5,6,7-tetrahydro-lH-indazole-l -carboxylate.

[0198] Ή NMR (400 MHz, DMSO-t/6) δ ppm 8.75 (s, 1 H), 7.39 - 7.53 (m, 4 H),

4.24 - 4.33 (m, 2 H), 4.06 (q, J=7.04 Hz, 2 H), 2.84 - 3.06 (m, 2 H), 2.54 - 2.63 (m, 1 H), 1.82 (dd, J=13.30, 3.13 Hz, 2 H), 1.37 - 1.51 (m, 8 H), 1.13 - 1.20 (m, 3 H); Method 1 , retention time: 4.771 min; HRMS: m/z (M+H)⁺ = 381.1571 (Calculated for Ci₉H₂₆ClN₂0₄ =

381.1576).

EXAMPLE 14

[00108] This example demonstrates a synthesis ofan embodiment of a compound of the invention.

[00109] The synthesis is depicted in Scheme 7.

Scheme 7

[0199] Scheme 7, Step 1. The title product was prepared according to the method used to prepare compound described inScheme 4, Step 3 above, substituting 2-(2- chlorophenyl)acetic acid for picolinic acid and substituting ethyl l-(2-amino-2- methylpropanoyl)piperidine-4-carboxylate for tert-butyl 4-amino-4,5,6,7-tetrahydro-l H- indazole- 1 -carboxylate.

[0200] Ή NMR (400 MHz, DMSO- 6) δ ppm 8.40 (s, 1 H), 7.37 - 7.44 (m, 1 H),

7.30 - 7.35 (m, 1 H), 7.22 - 7.29 (m, 2 H), 4.16 - 4.26 (m, 2 H), 4.01 - 4.09 (m, 2 H), 3.58 (s, 2 H), 2.76 - 2.98 (m, 3 H), 2.51 - 2.57 (m, 2 H), 1.75 (dd, J=13.1 1, 3.33 Hz, 2 H), 1.32 - 1.38 (m, 6 H), 1.13 - 1.20 (m, 3 H); Method 1, retention time: 4.989 min; HRMS: m/z (M+H)⁺ = 395.1722 (Calculated for C20H₂8CIN2O4 = 395.1732).

EXAMPLE 15

[00110] This example demonstrates a synthesis of an exemplary intermediate for a compound of formula (II) in accordance with an embodiment of a compound of the invention.

[00111] The synthesis is depicted in Scheme 8.

Scheme 8

[0201] Scheme 8, Step 1. To a solution of 2-(3,4-diethoxyphenyl)acetonitrile (0.2 g,

0.974 mmol) in t-BuOH (5 ml) was added a solution of potassium fer/-butoxide (0.109 g, 0.974 mmol) in t-BuOH (2.5ml) and subsequently methyl iodide (0.067 ml, 1.072 mmol).

The mixture was stirred at r.t. for lh, 40°C for lh, and reflux for 2h. The reaction mixture was concentrated and the residue diluted DCM. The organic layer was washed with water, dried over Na2S04, and concentrated. The crude product was purified by Biotage, eluting with a hexanes-EtOAc gradient, to afford title product. LCMS: : m/z (M+H)⁺ = 220.1.

[0202] Scheme 8, Step 2. To a solution of 2-(3,4-diethoxyphenyl)propanenitrile ( 130 mg, 0.593 mmol) in THF (3 ml) was added slowly borane-methyl sulfide complex (0.593 ml, 1.186 mmol) (2.0M in THF). After the reaction mixture was refluxed for overnight, it was quenched with methanol and concentrated in vacuuo. The crude product was used in the next reaction without further purification.

[0203] Ή NMR (400 MHz, CHLOROFORM-d) δ ppm 6.84 (d, J=8.22 Hz, 1 H),

6.70 - 6.76 (m, 2 H), 4.09 (dq, J=8.61 , 7.04 Hz, 4 H), 3.70 (br. s., 1 H), 2.77 - 2.85 (m, 2 H), 2.64 - 2.71 (m, 1 H), 1.66 - 1.72 (m, 1 H), 1.44 (td, J=6.95, 3.33 Hz, 6 H), 1.23 (d, J=7.04 Hz, 3 H).

EXAMPLE 16

[00112] This example demonstrates a synthesis of an exemplary intermediate for a compound of formula (II) in accordance with an embodiment of a compound of the invention.

[00113] The synthesis is depicted in Scheme 9.

Scheme 9

[0204] Scheme 9, Step 1. To a solution of 2-(3,4-diethoxyphenyl)acetonitrile (0.2 g,

0.974 mmol) in DCM (9 ml) was added dropwise BBr3 (3.90 ml, 3.90 mmol). The mixture was stirred at r.t. for 3hrs. The solvent was removed. The crude product was purified by Biotage, eluting with a DCM-MeOH gradient, to give title product.

[0205] Scheme 9, Step 2. To a mixture of 2,2,2-trifluoroethyl

trifluoromethanesulfonate (322 mg, 1.388 mmol) and potassium carbonate (192 mg, 1.388 mmol) in aceton (2 ml) was added dropwise a solution of 2-(3,4-dihydroxyphenyl)acetonitrile (90 mg, 0.603 mmol) in aceton (2 ml). The mixture was refluxed for 4hrs. The solvent was removed. The residue was mixed with water and EtOAc. The organic layer was washed with water and brine, dried over Na2SC> , and concentrated. The crude product was used in the next reaction without purification.

[0206] ^!H NMR (400 MHz, CHLOROFORM-i ) δ ppm 6.94 - 7.08 (m, 3 H), 4.41

(qd, J=8.09, 6.65 Hz, 4 H), 3.72 (s, 2 H).

[0207] Scheme 9, Step 3. To a solution of 2-(3,4-bis(2,2,2- trifluoroethoxy)phenyl)acetonitrile (0.18 g, 0.575 mmol) in THF (3 ml) was added slowly borane-methyl sulfide complex (0.575 ml, 1.149 mmol) (2.0M in THF). After the reaction mixture was refluxed for overnight, it was quenched with methanol and concentrated in vacuuo. The crude product was used in the next reaction without further purification. LCMS: w/z (M+H)⁺ = 318.1.

EXAMPLE 17

[00114] This example demonstrates a synthesis of an embodiment of a compound of the invention.

[00115] The synthesis is depicted in Scheme 10.

Scheme 10

[0208] Scheme 10, Step 1. To a solution of ethyl 4H-thieno[3,2-b]pyrrole-5- carboxylate (0.3 g, 1.537 mmol) in DMF (5 ml) was added NaH (0.055 g, 2.305 mmol). The mixture was stirred at r.t. for l Omin, and benzyl bromide (0.219 ml, 1.844 mmol) was added to the mixture. The reaction mixture was stirred at r.t. for overnight. H20 was slowly added to the mixture. The organic layer was washed with Sat. NaHC0₃ (3X) and brine, dried over Na₂S0₄, and concentrated. The crude product was purified by Biotage, eluting with a hexanes-EtOAc gradient, gave title product.

[0209] Scheme 10, Step 2. To a solution of ethyl 4-benzyl-4H-thieno[3,2-b]pyrrole-

5-carboxylate (0.245 g, 0.859 mmol) in dioxane (1 1 ml) was added KOH (4 ml, 16.00 mmol) (4M). The mixture was heated to reflux for lday. After cooled, the mixture was acidified with HC1 (cone). Solid was filtered and dried. The crude product was used in the next reaction without further purification.

[0210] Scheme 10, Step 3. Hydroxylamine hydrochloride (0.068 g, 0.974 mmol) and potassium hydroxide (0.055 g, 0.974 mmol) were dissolved in MeOH (8 ml) and stirred at r.t. for 0.5 h. 2-(3,4-diethoxyphenyl)acetonitrile (0.2 g, 0.974 mmol) was added to the mixture. The reaction mixture was heated to reflux for 6.5 hrs. After filtration of inorganic salts, the solvent was evaporated under reduced pressure. The crude product was purified by Biotage, eluting with a DCM-MeOH gradient, afforded title product.

[0211] Scheme 10, Step 4. 4-Benzyl-4H-thieno[3,2-b]pyrrole-5-carboxylic acid (64 mg, 0.249 mmol) and CDI (44.4 mg, 0.274 mmol) were dissolved in DMF (2 ml). After stirring the solution at r.t. for 3 hrs, (Z)-2-(3,4-diethoxyphenyl)-N'-hydroxyacetimidamide (65.2 mg, 0.274 mmol) and potassium carbonate (103 mg, 0.746 mmol) were added .The reaction mixture was heated at 90°C for 2hrs. The solid was filtered off. The crude product was purified by reverse phase purification system to give the title product as a TFA salt.

[0212] Ή NMR (400 MHz, DMSO-d6) δ ppm 7.63 (d, J=5.48 Hz, 1 H), 7.46 (s, 1 H),

7.28 (d, J=5.48 Hz, 1 H), 7.17 - 7.23 (m, 3 H), 7.05 - 7.10 (m, 2 H), 6.93 (d, J=1.96 Hz, 1 H), 6.85 - 6.90 (m, 1 H), 6.77 - 6.82 (m, 1 H), 5.86 (s, 2 H), 4.02 (s, 2 H), 3.98 (q, J=7.04 Hz, 2 H), 3.92 (q, J=6.78 Hz, 2 H), 1.28 (dt, J=1 1.84, 6.99 Hz, 6 H) Method 1 , retention time: 3.421 min; HRMS: m/z (M+H)⁺ = 460.1674 (Calculated for C₂₆H₂₆N₃0₃S = 460.1689).

EXAMPLE 18

[00116] This example demonstrates a synthesis of an exemplary embodiment of a compound of Formula II of the invention.

[00117] The synthesis is depicted in Scheme 1 1.

Scheme 11

[0213] Scheme 11, Stepl. To a solution of 4-benzyl-N-(3,4-diethoxyphenethyl)-4H- thieno[3,2-b]pyrrole-5-carboxamide (30 mg, 0.067 mmol) in DMF (0.7 ml) was added NaH (4.81 mg, 0.201 mmol). The mixture was stirred at r.t. for l Omin. To the mixture was added methyl iodide (5.02 μΐ, 0.080 mmol). The reaction mixture was stirred at r.t. for 3 hrs. Water was added to the mixture, and then purified by reverse phase purification system to give the title product as a TFA salt.

[0214] Ή NMR (400 MHz, DMSO-c 6) 5 ppm 7.35 (d, J=5.48 Hz, 1 H), 7.19 - 7.30 (m, 3 H), 7.07 - 7.14 (m, 3 H), 6.80 (d, J=8.22 Hz, 1 H), 6.60 (br. s., 3 H), 5.32 (br. s., 2 H), 3.84 - 3.98 (m, 4 H), 3.56 (t, J=7.43 Hz, 2 H), 2.96 (s, 3 H), 2.62 - 2.70 (m, 2 H), 1.21 - 1.33 (m, 6 H); Method 1 , retention time: 3.338 min; HRMS: m/z (M+H)⁺ = 463.2039 (Calculated for C₂₇H₃iN₂0₃S = 463.2050).

EXAMPLE 19

[00118] This example demonstrates a synthesis of an exemplary embodiment of a compound of Formula II of the invention.

[00119] The synthesis is depicted in Scheme 12.

Scheme 12

[0215] Scheme 12, Step 1. To a solution of N-(3,4-diethoxyphenethyl)-4H-thieno[3,2- b]pyrrole-5-carboxamide (50 mg, 0.139 mmol) and triphenylphosphine (47.6 mg, 0.181 mmol) in THF (2ml) was added dropwise a solution of 1 -phenylethanol (0.019 ml, 0.153 mmol) in THF (0.5ml). Then a solution of di-tert-butyl azodicarboxylate (42.4 mg, 0.184 mmol) in THF (1ml) was added, and the reaction mixture was allowed to stir at r.t. for 2.5 days. The solvent was removed. DMF was added to the mixture, and then purified by reverse phase purification system to give the title product as a TFA salt.

[0216] Ή NMR (400 MHz, DMSO-i 6) δ ppm 8.37 (t, J=5.67 Hz, 1 H), 7.27 - 7.34

(m, 3 H), 7.20 - 7.27 (m, 3 H), 7.00 (d, J=0.78 Hz, 1 H), 6.88 (q, J=7.30 Hz, 1 H), 6.81 - 6.85 (m, 2 H), 6.70 - 6.74 (m, 2 H), 3.96 (qd, J=7.04, 4.70 Hz, 4 H), 3.40 - 3.47 (m, 2 H), 2.76 (t, J=7.43 Hz, 2 H), 1.84 (d, J=7.04 Hz, 3 H), 1.28 (q, J=7.04 Hz, 6 H); Method 1 , retention time: 6.967 min; HRMS: m/z (M+H)⁺ = 463.2047 (Calculated for C₂₇H3 iN₂0₃S = 463.2050). EXAMPLE 20

[00120] This example demonstrates a synthesis of an exemplary intermediate for a compound of formula (II) in accordance with an embodiment of a compound of the invention.

[00121] The synthesis is depicted in Scheme 13.

Scheme 13

[0217] Scheme 13, Step 1. To a solution of 1 -(chloromethyl)-2-fluoro-4,5- dimethoxybenzene (0.5 g, 2.443 mmol) in DMSO (Volume: 25 ml) was added sodium cyanide (0.150 g, 3.05 mmol). The mixture was stirred at r.t. for 1.5hrs. The resulting mixture was poured into 100 ml of water, extracted with EtOAc (2X). The organic phase was dried over Na2S04 and concentrated. Crystallization of the solid in hexane-DCM gave 0.21g (44%) of the desired cyanide.

[0218] Scheme 13, Step 2. To a solution of 2-(2-fluoro-4,5- dimethoxyphenyl)acetomtrile (0.3 g, 1.537 mmol) in DCM (15 ml) was added BBr₃ (4.61 ml, 4.61 mmol) (1.0M in DCM) with cooling in an ice bath. The reaction mixture was stirred at r.t. for 1 hr. The solvent was removed. The crude product was purified by Biotage, eluting with a DCM-MeOH gradient, to afford title product.

[0219] Scheme 13, Step 3. To a solution of 2-(2-fluoro-4,5-dihydroxyphenyl)acetonitrile (83 mg, 0.497 mmol) in DMF (5 ml) was added potassium carbonate (206 mg, 1.49 mmol), and then bromoethane (0.074 ml, 0.993 mmol). The mixture was heated at 80 °C for overnight. Water was added to the mixture. The organic layer was washed with Sat. NaHC03 (3X) and brine, and dried over Na2S04, and concentrated. The crude product was purified by Biotage, eluting with a DCM-MeOH gradient, gave title product. [0220] Scheme 13, Step 4. . The title product was prepared according to the method used to prepare compound described inScheme 8, Step 2 above, substituting 2-(4,5-diethoxy- 2-fluorophenyl)acetonitrile for 2-(3,4-diethoxyphenyl)propanenitrile. LCMS: m/z (M+H)⁺ = 228.1.

EXAMPLE 21

[0221] This example sets forth characterization data for several representative embodiments of the invention.

[0222] NCGC00238537 (LLI01-002)

N-(l-(2,4-difluorophenyl)-4,5,6,7-tetrahydro-lH-indazol-4-yl)benzamide

Ή NMR (400 MHz, DMSO- 6) δ ppm 8.67 (d, J=7.63 Hz, 1 H), 7.88 - 7.94 (m, 2 H), 7.40 - 7.62 (m, 6 H), 7.23 - 7.31 (m, 1 H), 5.13 - 5.22 (m, 1 H), 2.50 (dt, J=3.42, 1.81 Hz, 2 H), 1.94 - 2.03 (m, 2 H), 1.72 - 1.80 (m, 2 H); Method 1, retention time: 5.440 min; HRMS: m/z (M+H)⁺ = 354.1406 (Calculated for C₂0H₁8F2N3O = 354.1412).

[0223] NCGC00238560 (LLIOl-01 1)

N-(l-(2,4-difluorophenyl)-4,5,6,7-tetrahydro-lH-indazol-4-yl)-l,2,5-oxadiazole-3- carboxamide

Ή NMR (400 MHz, DMSO-i 6) δ ppm 8.76 (d, J=8.22 Hz, 1 H), 7.52 - 7.61 (m, 4 H), 7.23 - 7.30 (m, 1 H), 5.00 - 5.09 (m, 1 H), 2.41 - 2.48 (m, 2 H), 1.87 - 1.98 (m, 2 H), 1.68 - 1.78 (m, 2 H); Method 1 , retention time: 4.969 min; HRMS: m/z (M+H)⁺ = 346.1 104 (Calculated for C₁₆H₁₄F₂N₅0₂ = 346.1 1 10). [0224] NCGC00238547 (LLI01-012)

N-(l-(2,4-difluorophenyl)-4,5,6,7-tetrahydro-lH-indazol-4-yl)cyclopropanecarboxamide

Ή NMR (400 MHz, DMSO- 6) δ ppm 8.37 (d, J=7.83 Hz, 1 H), 7.50 - 7.63 (m, 3 H), 7.22 - 7.31 (m, J=8.56, 8.56, 2.84, 1.57 Hz, 1 H), 4.85 - 4.94 (m, 1 H), 2.45 (q, J=5.74 Hz, 2 H), 1.80 - 1.90 (m, 2 H), 1.67 - 1.78 (m, 1 H), 1.54 - 1.64 (m, 2 H), 0.58 - 0.77 (m, 4 H); Method 1, retention time: 4.870 min; HRMS: m/z (M+H)⁺ = 318.1420 (Calculated for C₁₇Hi₈F₂N₃0 = 318.1412).

[0225] NCGC00238548 (LLIOl-013)

Ή NMR (400 MHz, DMSO-c?6) δ ppm 8.72 (d, J=8.22 Hz, 1 H), 7.87 (dd, J=3.91 , 1.17 Hz, 1 H), 7.75 (dd, J=4.70, 1.17 Hz, 1 H), 7.52 - 7.63 (m, 3 H), 7.22 - 7.31 (m, J=8.56, 8.56, 2.84, 1.17 Hz, 1 H), 7.13 (dd, J=4.89, 3.72 Hz, 1 H), 5.08 - 5.17 (m, 1 H), 2.49 (br. s., 2 H), 1.92 - 2.03 (m, 2 H), 1.67 - 1.82 (m, 2 H); Method 1 , retention time: 5.386 min; HRMS: m/z (M+H)⁺ = 360.0974 (Calculated for

360.0977).

[0226] NCGC00238559 (LLI01 -014)

1H NMR (400 MHz, DMSO-i/6) δ ppm 8.50 (d, J=8.22 Hz, 1 H), 8.22 (dd, J=2.74, 1.57 Hz, 1 H), 7.52 - 7.63 (m, 5 H), 7.22 - 7.31 (m, 1 H), 5.09 - 5.18 (m, 1 H), 3.34 - 3.45 (m, 2 H), 1.92 - 2.02 (m, 2 H), 1.74 (td, J=10.86, 6.46 Hz, 2 H); Method 1, retention time: 5.321 min;

HRMS: m/z (M+H)⁺ = 360.0975 (Calculated for Ci₈H₁₆F₂N₃OS = 360.0977).

[0227] NCGC00238557 (LL101 -015)

1H NMR (400 MHz, DMSO-c 6) δ ppm 8.89 (d, J=8.22 Hz, 1 H), 8.01 - 8.10 (m, 2 H), 7.65 - 7.83 (m, 5 H), 7.50 - 7.64 (m, 5 H), 7.20 - 7.30 (m, 1 H), 5.18 (td, J=2.25, 0.98 Hz, 1 H), 2.40 - 2.56 (m, 2 H), 1.92 - 2.04 (m, 2 H), 1.69 - 1.84 (m, 2 H); Method 1, retention time: 6.071 min; HRMS: m/z (M+H)⁺ = 458.1679 (Calculated for C₂7H22F₂N30₂ = 458.1675).

[0228] NCGC00238558 (LLI01-016)

tart-Butyl 2-(l-(2,4-difluorophenyl)-4,5,6,7-tetrahydro-lH-indazol-4- ylcarbamoyl)piperidine-l-carboxylate

Ή NMR (400 MHz, DMSO-i 6) δ ppm 8.00 - 8.14 (m, 1 H), 7.43 - 7.63 (m, 3 H), 7.22 - 7.31 (m, 1 H), 4.86 - 4.96 (m, 1 H), 4.39 - 4.60 (m, 1 H), 3.79 (dd, J=l 1.54, 0.98 Hz, 1 H), 3.07 - 3.31 (m, 2 H), 2.39 - 2.48 (m, 2 H), 1.95 - 2.08 (m, 1 H), 1.80 - 1.94 (m, 2 H), 1.48 - 1.79 (m, 5 H), 1.19 - 1.46 (m, 10 H); Method 1, retention time: 6.095 min; HRMS: m/z (M+H)⁺ = 461.2360 (Calculated for C₂₄H₃₁F₂N₄0₃ = 461.2359).

[0229] NCGC00238556 (LLI01-018)

N-(l-(2,4-difluorophenyl)-4,5,6,7-tetrahydro-lH-indazol-4-yl)isonicotinamide

Ή NMR (400 MHz, DMSO-<f6) δ ppm 9.05 (d, J=7.83 Hz, 1 H), 8.77 (d, J=5.87 Hz, 2 H), 7.91 (d, J=6.26 Hz, 2 H), 7.51 - 7.66 (m, 3 H), 7.23 - 7.32 (m, 1 H), 5.12 - 5.23 (m, 1 H), 2.48 - 2.59 (m, 2 H), 1.99 (dd, J=10.17, 3.52 Hz, 2 H), 1.70 - 1.83 (m, 2 H); Method 1, retention time: 3.993 min; HRMS: m/z (M+H)⁺ = 355.1373 (Calculated for Ci₉Hi₇F₂N₄0 = 355.1365).

[0230] NCGC00238550 (LLI01-020)

N-(3,4-diethoxyphenethyl)-4-isopropyl-4H-thieno[3,2-b]pyrrole-5-carboxamide

Ή NMR (400 MHz, DMSO-i 6) δ ppm 8.25 (t, J=5.48 Hz, 1 H), 7.41 (d, J=5.09 Hz, 1 H), 7.30 (d, J=5.87 Hz, 1 H), 6.83 - 6.88 (m, 2 H), 6.82 (d, J=l .96 Hz, 1 H), 6.72 (dd, J=8.22, 1.96 Hz, 1 H), 5.59 (dt, J=13.79, 6.99 Hz, 1 H), 3.97 (qd, J=6.98, 4.50 Hz, 4 H), 3.37 - 3.44 (m, 2 H), 2.74 (t, J=7.24 Hz, 2 H), 1.44 (d, J-6.65 Hz, 6 H), 1.29 (td, J=6.95, 2.15 Hz, 6 H)Method 1 , retention time: 6.439 min; HRMS: m/z (M+H)⁺ = 401.1883 (Calculated for C₂₂H₂₉N₂0₃S = 401.1893). [0231] NCGC00092589 (LLI01 -021)

N-(3,4-diethoxyphenethyl)-4-methyI-4H-thieno[3,2-b]pyrrole-5-carboxamide

1H NMR (400 MHz, DMSO- 6) 6 ppm 8.24 (t, J=5.67 Hz, 1 H), 7.43 (d, J=5.48 Hz, 1 H), 7.18 (d, J=5.87 Hz, 1 H), 7.02 (s, 1 H), 6.79 - 6.88 (m, 2 H), 6.72 (dd, J=8.02, 2.15 Hz, 1 H), 3.90 - 4.02 (m, 7 H), 3.35 - 3.46 (m, 2 H), 2.74 (t, J=7.24 Hz, 2 H), 1.29 (td, J=6.95, 4.11 Hz, 6 H); Method 1, retention time: 6.023 min; HRMS: m/z (M+H)⁺ = 373.1579 (Calculated for C₂₀H₂₅N₂O₃S = 373.1580).

[0232] NCGC00238551 (LLI01-022)

4-BenzyI-N-(3,4-diethoxyphenethyl)-4H-thieno[3,2-b]pyrrole-5-carboxamide

^!H NMR (400 MHz, DMSO-^6) δ ppm 8.31 (t, J=5.58 Hz, 1 H), 7.41 (d, J=5.28 Hz, 1 H), 7.17 - 7.29 (m, 3 H), 7.10 - 7.17 (m, 3 H), 7.08 (s, 1 H), 6.82 (d, J=8.22 Hz, 1 H), 6.79 (d, J=l .96 Hz, 1 H), 6.68 (dd, J=8.22, 1.96 Hz, 1 H), 5.78 (s, 2 H), 3.95 (qd, J=6.98, 3.52 Hz, 4 H), 3.36 - 3.44 (m, 2 H), 2.72 (t, J=7.24 Hz, 2 H), 1.28 (dt, J=9.88, 6.99 Hz, 6 H); Method 1 , retention time: 6.671 min; HRMS: m/z (M+H)⁺ = 449.1897 (Calculated for C₂₆H₂₉N₂0₃S = 449.1893).

[0233] NCGC00238549 (LLI01 -023)

N-(3,4-dimethoxybenzyl)-4-ethyl-4H-thieno[3,2-b]pyrrole-5-carboxamide Ή NMR (400 MHz, DMSO-i 6) 5 ppm 8.69 (t, J=6.06 Hz, 1 H), 7.44 (d, J=5.09 Hz, 1 H), 7.21 (d, J=4.70 Hz, 1 H), 7.1 1 (s, 1 H), 6.94 (d, J=1.96 Hz, 1 H), 6.87 - 6.92 (m, 1 H), 6.80 - 6.86 (m, 1 H), 4.53 (q, J=7.04 Hz, 2 H), 4.38 (d, J=6.26 Hz, 2 H), 3.73 (s, 3 H), 3.72 (s, 3 H), 1.27 (t, J=7.04 Hz, 3 H); Method 1 , retention time: 5.587 min; HRMS: m/z (M+H)⁺ =

345.1258 (Calculated for C18H21N2O3S = 345.1267).

[0234] NCGC00238552 (LLIO 1-025)

Ή NMR (400 MHz, DMSO- 6) δ ppm 7.96 (d, J=7.83 Hz, 1 H), 7.51 - 7.64 (m, 2 H), 7.48 (s, 1 H), 7.20 - 7.30 (m, 1 H), 4.80 - 4.92 (m, 1 H), 2.36 - 2.47 (m, 2 H), 2.13 (tt, J=l 1.59, 3.28 Hz, 1 H), 1.79 - 1.95 (m, 2 H), 1.48 - 1.77 (m, 7 H), 1.30 - 1.45 (m, 2 H), 1.10 - 1.27 (m, 3 H); Method 1 , retention time: 5.679 min; HRMS: m/z (M+H)⁺ = 360.1885 (Calculated for C₂₀H₂₄F₂N₃O = 360.1882).

[0235] NCGC00238553 (LLIO 1-026)

N-(l-(2,4-difluorophenyl)-4,5,6,7-tetrahydro-lH-indazol-4-yl)-lH-pyrazoIe-3- carboxamide

Ή NMR (400 MHz, DMSO-i 6) δ ppm 7.91 - 8.03 (m, 1 H), 7.46 - 7.67 (m, 3 H), 7.20 - 7.34 (m, 2 H), 6.69 (t, J=2.15 Hz, 1 H), 5.05 - 5.17 (m, 1 H), 4.64 - 4.79 (m, 1 H), 2.50 - 2.62 (m, 2 H), 1.88 - 2.09 (m, 2 H), 1.65 - 1.87 (m, 2 H); Method 1 , retention time: 4.558 min; HRMS: m/z (M+H)⁺ = 344.1307 (Calculated for CvH^NsO = 344.1317). [0236] NCGC00238539 (LLIO 1-030)

Ή NMR (400 MHz, DMSO- 6) 5 ppm 7.49 - 7.63 (m, 3 H), 7.44 (d, J=8.22 Hz, 1 H), 7.21 - 7.30 (m, J=8.51 , 8.51, 2.74, 1.37 Hz, 1 H), 4.91 - 5.03 (m, 1 H), 4.09 (t, J=3.91 Hz, 2 H), 3.99 (q, J=3.65 Hz, 2 H), 2.38 - 2.48 (m, 2 H), 2.16 - 2.22 (m, 3 H), 1.80 - 1.96 (m, 2 H), 1.71 (ddd, J=l 1.54, 6.06, 5.87 Hz, 2 H); Method 1 , retention time: 5.380 min; HRMS: m/z (M+H)⁺ = 376.1467 (Calculated for C₁₉H2oF₂N₃0₃ = 376.1467).

[0237] NCGC00238554 (LLI01-046_2^nd)

N-(l-(4-fluorophenyl)-lH-indazol-4-yl)picolinamide

Ή NMR (400 MHz, DMSO-i 6) δ ppm 10.94 (s, 1 H), 8.82 (dt, J=4.84, 0.81 Hz, 1 H), 8.48 (s, 1 H), 8.23 (dd, J=7.73, 0.88 Hz, 1 H), 8.06 - 8.16 (m, 1 H), 7.70 - 7.85 (m, 4 H), 7.56 - 7.62 (m, 1 H), 7.41 - 7.55 (m, 3 H); Method 1 , retention time: 6.170 min; HRMS: m/z (M+H)⁺ = 333.1 137 (Calculated for Ci₉Hi₄FN₄0 = 333.1 146).

[0238] NCGC00238541 (LLI01-050)

N-(l-(2,4-difluorophenyl)-4,5,6,7-tetrahydro-lH-indazol-4-yl)pyrazine-2-carboxamide

1H NMR (400 MHz, DMSO- 6) δ ppm 9.24 (d, 7=1.37 Hz, 1 H), 8.87 (d, 7=2.54 Hz, 1 H), 8.83 (d, 7=8.22 Hz, 1 H), 8.72 (dt, 7=2.54, 1.27 Hz, 1 H), 7.51 - 7.65 (m, 3 H), 7.22 - 7.31 (m, 1 H), 5.14 - 5.24 (m, 1 H), 2.41 - 2.56 (m, 2 H), 1.92 - 2.02 (m, 2 H), 1.83 - 1.92 (m, 1 H), 1.71 - 1.82 (m, 1 H); Method 1, retention time: 4.971 min; HRMS: m/z (M+H)⁺ = 356.1325 (Calculated for C₁₈H₁₆F₂N₅0 = 356.1317).

[0239] NCGC00241413 (LLI01-091)

N-(3,4-diethoxyphenethyl)acetamide

Ή NMR (400 MHz, DMSO-76) δ ppm 7.93 (t, 7=5.28 Hz, 1 H), 6.92 (d, 7=8.22 Hz, 1 H), 6.86 (d, 7=1.96 Hz, 1 H), 6.75 (dd, 7=8.02, 2.15 Hz, 1 H), 4.06 (dq, 7=12.33, 6.98 Hz, 4 H), 3.24 - 3.34 (m, 2 H), 2.68 (t, 7=7.43 Hz, 2 H), 1.86 (s, 3 H), 1.39 (td, 7=6.85, 5.87 Hz, 6 H); Method 1, retention time: 4.369 min; HRMS: m/z (M+H)⁺ = 252.1596 (Calculated for Ci₄H₂₂N0₃ = 252.1594).

[0240] NCGC00241414 (LLI01-094)

N-(3,4-diethoxyphenethyl)-2-(dimethylamino)acetamide

1H NMR (400 MHz, DMSO-76) δ ppm 8.44 - 8.52 (m, 1 H), 6.84 (d, 7=7.83 Hz, 1 H), 6.80 (d, 7=1.96 Hz, 1 H), 6.69 (dd, 7=8.02, 2.15 Hz, 1 H), 3.98 (dq, 7=14.09, 7.04 Hz, 4 H), 3.76 (br. s., 2 H), 3.32 - 3.39 (m, 2 H), 2.71 (s, 6 H), 2.66 (t, 7=7.24 Hz, 2 H), 1.30 (dt, 7=8.12, 6.90 Hz, 6 H); Method 1 , retention time: 3.573 min; HRMS: m/z (M+H)⁺

(Calculated for Ci₆H₂7N₂03 = 295.2016).

[0241] NCGC00241415 (LLI01-095)

N-(3,4-diethoxyphenethyl)thiophene-2-carboxamide

Ή NMR (400 MHz, DMSO-i 6) δ ppm 8.52 (t, J=5.48 Hz, 1 H), 7.72 (ddd, J=5.87, 4.50, 0.98 Hz, 2 H), 7.04 - 7.21 (m, 1 H), 6.85 (d, J=7.83 Hz, 1 H), 6.80 (d, J=1.96 Hz, 1 H), 6.71 (dd, J=8.02, 2.15 Hz, 1 H), 3.91 - 4.01 (m, 4 H), 3.37 - 3.46 (m, 2 H), 2.74 (t, J=7.43 Hz, 2 H), 1.29 (td, J=7.04, 3.52 Hz, 6 H); Method 1, retention time: 5.343 min; HRMS: m/z (M+H)⁺ = 320.1320 (Calculated for Ci₇H₂₂N0₃S = 320.1315).

[0242] NCGC00241416 (LLI01-096)

N-(3,4-diethoxyphenethyl)-l,2,5-oxadiazole-3-carboxamide

Ή NMR (400 MHz, DMSO- 6) 5 ppm 8.50 (t, J=5.87 Hz, 1 H), 6.84 (d, J=7.83 Hz, 1 H), 6.77 (d, J=1.96 Hz, 1 H), 6.68 (dd, J=8.22, 1.96 Hz, 1 H), 3.97 (quin, J=7.14 Hz, 4 H), 3.34 - 3.42 (m, 2 H), 2.70 (t, J=7.43 Hz, 2 H), 1.30 (td, J=7.04, 3.91 Hz, 6 H); Method 1 , retention time: 4.927 min; HRMS: m/z (M+H)⁺ = 306.1443 (Calculated for Ci₅H₂₀N₃O₄ = 306.1448).

[0243] NCGC00241417 (LLI01 -097)

N-(3,4-diethoxyphenethyl)benzamide

H NMR (400 MHz, DMSO-i 6) δ ppm 8.50 (t, J=5.48 Hz, 1 H), 7.78 - 7.85 (m, 2 H), 7.48 - 7.55 (m, 1 H), 7.41 - 7.48 (m, 2 H), 6.85 (d, J=8.22 Hz, 1 H), 6.81 (d, J=l .96 Hz, 1 H), 6.72 (dd, J=7.83, 1.96 Hz, 1 H), 3.96 (q, J=7.04 Hz, 4 H), 3.41 - 3.49 (m, 2 H), 2.76 (t, J=7.43 Hz, 2 H), 1.29 (td, J=7.04, 3.13 Hz, 6 H); Method 1 , retention time: 5.407 min; HRMS: m/z (M+H)⁺ = 314.1752 (Calculated for C9H₂₄NO₃ = 314.1751).

[0244] NCGC00241418 (LLI01 -098)

N-(3,4-diethoxyphenethyl)-3-methyl-5,6-dihydro-l,4-dioxine-2-carboxamide

Ή NMR (400 MHz, DMSO- 6) δ ppm 7.54 (t, J=5.87 Hz, 1 H), 6.84 (d, J=8.22 Hz, 1 H), 6.76 (d, J=1.96 Hz, 1 H), 6.67 (dd, J=8.22, 1.96 Hz, 1 H), 4.05 - 4.10 (m, 2 H), 3.91 - 4.03 (m, 6 H), 3.24 - 3.31 (m, 2 H), 2.60 - 2.69 (m, 2 H), 2.15 (s, 3 H), 1.25 - 1.35 (m, 6 H);

Method 1 , retention time: 5.368 min; HRMS: m/z (M+H)⁺ = 336.1804 (Calculated for C₁₈H₂₆N0₅ = 336.1805).

[0245] NCGC00241419 (LLI01-099)

N-(3,4-diethoxyphenethyl)picolinamide

Ή NMR (400 MHz, DMSO-c 6) δ ppm 8.75 (t, J=6.06 Hz, 1 H), 8.62 (td, J=2.93, 1.57 Hz, 1 H), 7.93 - 8.06 (m, 2 H), 7.56 - 7.65 (m, 1 H), 6.84 (d, J=8.22 Hz, 1 H), 6.81 (d, J=1.96 Hz, 1 H), 6.72 (dd, J=8.02, 2.15 Hz, 1 H), 3.96 (qd, J=6.91 , 2.74 Hz, 4 H), 3.45 - 3.56 (m, 2 H), 2.77 (t, J=7.43 Hz, 2 H), 1.28 (q, J=6.91 Hz, 6 H); Method 1 , retention time: 5.345 min; HRMS: m/z (M+H)⁺ = 315.1706 (Calculated for C 18H23N2O3 = 315.1703).

[0246] NCGC00241420 (LLI02-001)

N-(3,4-diethoxyphenethyl)-2-phenylacetamide Ή NMR (400 MHz, DMSO-i/6) δ ppm 8.04 (t, J=5.48 Hz, 1 H), 7.24 - 7.30 (m, 2 H), 7.17 - 7.23 (m, 3 H), 6.82 (d, J=7.83 Hz, 1 H), 6.75 (d, J=1.96 Hz, 1 H), 6.64 (dd, J=8.02, 2.15 Hz,

2 H), 1.29 (t, J=6.85 Hz, 6 H); Method 1 , retention time: 5.342 min; HRMS: m/z (M+H)⁺ = 328.191 1 (Calculated for C₂₀H₂₆NO₃ - 328.1907).

[0247] NCGC00241421 (LLI02-002)

N-(3,4-diethoxyphenethyl)-l-phenylcyclopropanecarboxamide

1H NMR (400 MHz, DMSO- 6) 5 ppm 7.24 - 7.35 (m, 5 H), 6.79 (d, J=7.83 Hz, 1 H), 6.67 (d, J=1.96 Hz, 1 H), 6.54 (dd, J=8.02, 2.15 Hz, 1 H), 6.45 (t, J=5.67 Hz, 1 H), 3.96 (qd, J=6.91, 5.48 Hz, 4 H), 3.15 - 3.25 (m, 2 H), 2.54 (t, J=7.24 Hz, 4 H), 1.26 - 1.34 (m, 6 H), 0.93 (q, J=3.52 Hz, 2 H); Method 1 , retention time: 6.036 min; HRMS: m/z (M+H)⁺ = 354.2059 (Calculated for C₂₂H₂₈N0₃ = 354.2064).

[0248] NCGC00241422 (LLI02-003)

N-(3,4-diethoxyphenethyl)benzofuran-2-carboxamide

Ή NMR (400 MHz, DMSO-i/6) 5 ppm 8.74 (t, J=5.87 Hz, 1 H), 7.76 (dt, J=7.83, 0.98 Hz, 1 H), 7.59 - 7.68 (m, 1 H), 7.50 (d, J=0.78 Hz, 1 H), 7.42 - 7.49 (m, 1 H), 7.33 (td, J=7.53, 0.98 Hz, 1 H), 6.79 - 6.88 (m, 2 H), 6.72 (dd, J=8.02, 2.15 Hz, 1 H), 3.96 (q, J=7.04 Hz, 4 H), 3.43 - 3.52 (m, 2 H), 2.77 (t, J=7.43 Hz, 2 H), 1.27 (dt, J=12.03, 6.90 Hz, 6 H); Method 1 , retention time: 5.870 min; HRMS: m/z (M+H)⁺ = 354.1716 (Calculated for C₂₁H₂₄N0₄ = 354.1700).

[0249] NCGC00251423 (LLI02-004)

N-(3,4-diethoxyphenethyl)-2,3-dihydrobenzo[b] [l,4]dioxine-2-carboxamide

Ή NMR (400 MHz, DMSO-76) δ ppm 8.12 (t, 7=5.67 Hz, 1 H), 6.93 - 6.97 (m, 1 H), 6.84 - 6.91 (m, 3 H), 6.81 (d, 7=8.22 Hz, 1 H), 6.76 (d, J=1.96 Hz, 1 H), 6.62 (dd, J=8.02, 2.15 Hz, 1 H), 4.73 (dd, J=6.26, 2.74 Hz, 1 H), 4.30 (dd, J=l 1.35, 2.74 Hz, 1 H), 4.14 (dd, J=l 1.35, 6.26 Hz, 1 H), 3.97 (quin, J=7.04 Hz, 4 H), 3.27 - 3.37 (m, 2 H), 2.64 (t, J=7.24 Hz, 2 H), 1.29 (t, J=6.85 Hz, 6 H); Method 1 , retention time: 5.809 min; HRMS: m/z (M+H)⁺ = 372.1802 (Calculated for C₂iH₂₆N0₅ = 372.1805).

[0250] NCGC00241424 (LLI02-005)

1H NMR (400 MHz, DMSO-c/6) δ ppm 8.23 (t, 7=5.67 Hz, 1 H), 7.42 (d, 7=5.09 Hz, 1 H), 7.08 (d, J=5.87 Hz, 1 H), 6.98 (s, 1 H), 6.78 - 6.88 (m, 2 H), 6.71 (dd, 7=8.22, 1.96 Hz, 1 H), 5.18 - 5.27 (m, 1 H), 5.1 1 (d, J=7.04 Hz, 2 H), 3.96 (q, J=7.04 Hz, 4 H), 3.36 - 3.46 (m, 2 H), 2.74 (t, J=7.24 Hz, 2 H), 1.77 (s, 3 H), 1.64 (s, 3 H), 1.28 (q, J=7.04 Hz, 6 H); Method 1, retention time: 6.748 min; HRMS: m/z (M+H)⁺ = 427.2047 (Calculated for C₂₄H₃₁N₂0₃S = 427.2050).

[0251] NCGC00241425 (LLI02-006)

N-(3,4-diethoxyphenethyl)-4-(pyridin-3-ylmethyl)-4H-thieno[3,2-b]pyrrole-5- carboxamide

1H NMR (400 MHz, DMSO-76) 5 ppm 8.44 - 8.51 (m, 2 H), 8.35 (t, 7=5.67 Hz, 1 H), 7.53 - 7.60 (m, 1 H), 7.46 (d, J=5.48 Hz, 1 H), 7.37 (dd, 7=7.63, 4.89 Hz, 1 H), 7.25 (d, 7=5.48 Hz, 1 H), 7.13 (s, 1 H), 6.83 (d, J=8.22 Hz, 1 H), 6.79 (d, J=1.96 Hz, 1 H), 6.68 (dd, 7=7.83, 1.96 Hz, 1 H), 5.82 (s, 2 H), 3.95 (qd, 7=6.91 , 5.09 Hz, 4 H), 3.41 - 3.51 (m, 2 H), 2.72 (t, 7=7.43 Hz, 2 H), 1.28 (dt, J=10.66, 6.99 Hz, 6 H); Method 1 , retention time: 4.617 min; HRMS: m/z (M+H)⁺ = 450.1855 (Calculated for C₂₅H₂₈N₃0₃S = 450.1846).

[0252] NCGC00241426 (LLI02-007)

Ή NMR (400 MHz, DMSO- 6) δ ppm 8.29 (t, J=5.67 Hz, 1 H), 7.39 (d, J=5.48 Hz, 1 H), 7.08 - 7.15 (m, 2 H), 7.04 (s, 1 H), 6.96 - 7.02 (m, 2 H), 6.87 (d, J=7.43 Hz, 1 H), 6.75 - 6.83 (m, 2 H), 6.66 (dd, J=8.22, 1.96 Hz, 1 H), 5.71 (s, 2 H), 3.93 (qd, J=6.98, 4.70 Hz, 4 H), 3.34 - 3.43 (m, 2 H), 2.70 (t, J=7.24 Hz, 2 H), 2.19 (s, 3 H), 1.25 (dt, J=10.27, 6.90 Hz, 6 H); Method 1 , retention time: 6.811 min; HRMS: m/z (M+H)⁺ = 463.2057 (Calculated for C₂₇H₃iN₂0₃S = 463.2050).

[0253] NCGC00241427 (LLI02-008)

Ή NMR (400 MHz, DMSO- 6) δ ppm 8.32 (t, J=5.67 Hz, 1 H), 7.44 (d, J=5.48 Hz, 1 H), 7.23 (ddd, J=10.56, 9.39, 2.54 Hz, 1 H), 7.07 - 7.16 (m, 2 H), 6.90 - 7.02 (m, 1 H), 6.74 - 6.87 (m, 3 H), 6.67 (dd, J=8.12, 2.05 Hz, 1 H), 5.80 (s, 2 H), 3.95 (qd, J=6.98, 3.33 Hz, 4 H), 3.34 - 3.43 (m, 2 H), 2.70 (t, J=7.34 Hz, 2 H), 1.28 (dt, J=10.03, 7.02 Hz, 6 H); Method 1 , retention time: 6.765 min; HRMS: m/z (M+H)⁺ = 485.1729 (Calculated for C₂6H2₇F₂N20₃S = 485.1705).

[0254] NCGC00241428 (LLI02-009)

N-(3,4-diethoxyphenethyl)-4-(4-(difluoromethoxy)benzyl)-4H-thieno[3,2-b]pyrrole-5- carboxamide

1H NMR (400 MHz, DMSO-J6) δ ppm 8.28 - 8.34 (m, 1 H), 7.32 - 7.51 (m, 1 H), 7.14 - 7.23 (m, 3 H), 7.05 - 7.10 (m, 1 H), 6.95 - 6.99 (m, 1 H), 6.76 - 6.86 (m, 3 H), 6.69 (ddd, J=7.92, 4.01, 1.37 Hz, 2 H), 5.73 - 5.79 (m, 2 H), 3.94 (dd, J=12.13, 7.04 Hz, 4 H), 3.38 - 3.45 (m, 2 H), 2.82 - 2.89 (m, 2 H), 1.24 - 1.33 (m, 6 H); Method 1 , retention time: 6.664 min; HRMS: m/z (M+H)⁺ = 515.1814 (Calculated for C27H29F2N2O4S = 515.1811).

[0255] NCGC00241429 (LLI02-010)

Ή NMR (400 MHz, DMSO-d6) δ ppm 8.35 (t, J=5.67 Hz, 1 H), 7.49 (t, J=8.02 Hz, 1 H), 7.45 (d, J=5.48 Hz, 1 H), 7.15 - 7.22 (m, 2 H), 7.13 (s, 1 H), 6.93 (dd, J=8.22, 1.57 Hz, 1 H), 6.82 (d, J=7.83 Hz, 1 H), 6.79 (d, j=1.96 Hz, 1 H), 6.66 (dd, J=8.22, 1.96 Hz, 1 H), 5.77 (s, 2 H), 3.95 (qd, J=7.04, 5.09 Hz, 4 H), 3.37 - 3.44 (m, 2 H), 2.72 (t, J=7.24 Hz, 2 H), 1.27 (dt, j=12.42, 6.90 Hz, 6 H); Method 1 , retention time: 6.951 min; HRMS: m/z (M+H)⁺ =

501.1389 (Calculated for C₂₆H₂₇CIFN₂O₃S = 501.1409).

[0256] NCGC00241430 (LLI02-01 1)

5- carboxamide Ή NMR (400 MHz, DMSO-c 6) 5 ppm 9.20 (s, 1 H), 8.33 (t, J=5.67 Hz, 1 H), 8.20 (s, 1 H), 7.74 (d, J=8.61 Hz, 2 H), 7.44 (d, J=5.09 Hz, 1 H), 7.30 (d, J=8.61 Hz, 2 H), 7.21 (d, J=5.48 Hz, 1 H), 7.1 1 (s, 1 H), 6.77 - 6.84 (m, 2 H), 6.67 (dd, J=8.22, 1.96 Hz, 1 H), 5.83 (s, 2 H), 3.89 - 3.98 (m, 4 H), 3.36 - 3.45 (m, 2 H), 2.73 (t, J=7.04 Hz, 2 H), 1.21 - 1.31 (m, 6 H); Method 1, retention time: 5.994 min; HRMS: m/z (M+H)⁺ = 516.2071 (Calculated for C₂8H₃oN₅0₃S = 516.2064).

[0257] NCGC00241431 (LLI02-012)

N-(3,4-diethoxyphenethyl)-4-phenethyI-4H-thieno[3,2-b]pyrroIe-5-carboxamide

1H NMR (400 MHz, DMSO-i/6) δ ppm 8.23 (t, J=5.67 Hz, 1 H), 7.36 (d, J=5.48 Hz, 1 H), 7.21 - 7.27 (m, 2 H), 7.14 - 7.21 (m, 2 H), 7.06 (d, J=5.87 Hz, 1 H), 7.03 (s, 1 H), 6.80 - 6.86 (m, 2 H), 6.73 (dd, J=8.02, 1.76 Hz, 1 H), 6.51 (s, 1 H), 4.62 - 4.70 (m, 2 H), 3.89 - 4.00 (m, 4 H), 3.40 - 3.48 (m, 2 H), 2.90 - 2.98 (m, 2 H), 2.76 (t, J=7.24 Hz, 2 H), 1.27 (t, J=7.04 Hz, 6 H); Method 1 , retention time: 6.815 min; HRMS: m/z (M+H)⁺ - 463.2052 (Calculated for C₂₇H₃iN₂0₃S = 463.2050).

[0258] NCGC00241433 (LLI02-014)

N,4-dibenzyl-N-(3,4-dihydroxyphenethyl)-4H-thieno[3,2-b]pyrrole-5-carboxamide

Ή NMR (400 MHz, DMSO-i 6) δ ppm 1 1.65 (d, J=1.56 Hz, 2 H), 8.25 (t, J=5.67 Hz, 2 H), 7.23 - 7.51 (m, 10 H), 7.06 (dd, J=1.96, 0.78 Hz, 1 H), 6.91 - 6.99 (m, 3 H), 6.75 (dd, J=8.22, 1.96 Hz, 1 H), 5.06 (d, J=l 1.74 Hz, 3 H), 3.39 - 3.50 (m, 2 H), 2.75 (t, J=7.24 Hz, 2 H); Method 1 , retention time: 6.614 min; HRMS: m/z (M+H)⁺ = 483.1734 (Calculated for C29H₂₇N₂0₃S = 483.1737).

[0259] NCGC00241434 (LLI02-017)

N-(3,4-diethoxyphenethyl)-l-methyl-lH-indole-2-carboxamide

Ή NMR (400 MHz, DMSO- 6) δ ppm 8.52 (d, J=3.13 Hz, 1 H), 7.62 (dd, J=7.83, 2.74 Hz, 1 H), 7.51 (dd, J=8.02, 2.93 Hz, 1 H), 7.20 - 7.31 (m, 1 H), 7.09 (td, J=7.43, 3.13 Hz, 1 H), 7.01 (d, J=3.52 Hz, 1 H), 6.80 - 6.90 (m, 2 H), 6.74 (dd, J=8.02, 1.37 Hz, 1 H), 3.84 - 4.07 (m, 7 H), 3.45 (d, J=3.91 Hz, 2 H), 2.73 - 2.82 (m, 2 H), 1.21 - 1.37 (m, 6 H); Method 1 , retention time: 6.125 min; HRMS: m/z (M+H)⁺ = 367.2019 (Calculated for C22H₂₇N₂0₃ = 367.2016).

[0260] NCGC00241436 (LLI02-019)

3-Benzoyl-N-(3,4-diethoxyphenethyl)benzamide

Ή NMR (400 MHz, DMSO- 6) δ ppm 8.71 (d, J=2.35 Hz, 1 H), 8.17 (br. s., 1 H), 8.10 (d, J=7.83 Hz, 1 H), 7.86 (d, J=7.43 Hz, 1 H), 7.52 - 7.80 (m, 6 H), 6.76 - 6.90 (m, 2 H), 6.70 (d, J=7.83 Hz, 1 H), 3.95 (qd, J=6.91, 2.35 Hz, 4 H), 3.39 - 3.53 (m, 2 H), 2.70 - 2.82 (m, 2 H), 1.15 - 1.46 (m, J=7.24, 7.24, 7.04, 2.35 Hz, 6 H); Method 1, retention time: 6.045 min;

HRMS: m/z (M+H)⁺ = 418.2012 (Calculated for C₂₆H₂₈N0₄ = 418.2013).

[0261] NCGC00241437 (LLI02-020)

4-Benzoyl-N-(3,4-diethoxyphenethyl)benzamide

Ή NMR (400 MHz, DMSO- 6) δ ppm 8.72 (t, J=5.67 Hz, 1 H), 7.95 - 8.00 (m, 2 H), 7.78 - 7.82 (m, 2 H), 7.74 - 7.78 (m, 2 H), 7.68 - 7.74 (m, 1 H), 7.56 - 7.62 (m, 2 H), 6.86 (d, J=8.22 Hz, 1 H), 6.83 (d, J=1.96 Hz, 1 H), 6.73 (dd, J=8.02, 2.15 Hz, 1 H), 3.98 (qd, J=6.98, 3.33 Hz, 4 H), 3.46 - 3.53 (m, 2 H), 2.79 (t, J=7.43 Hz, 2 H), 1.30 (td, 6 H); Method 1 , retention time: 6.035 min; HRMS: m/z (M+H)⁺ = 418.2013 (Calculated for C26H28NO4 = 418.2013). [0262] NCGC00241440 (LLI02-024)

N-(3,4-diethoxyphenethyl)quinoline-2-carboxamide

Ή NMR (400 MHz, DMSO- 6) δ ppm 8.85 - 8.97 (m, 1 H), 8.57 (t, J=7.83 Hz, 1 H), 8.04 - 8.20 (m, 3 H), 7.83 - 7.93 (m, 1 H), 7.67 - 7.77 (m, 1 H), 6.81 - 6.92 (m, 2 H), 6.72 - 6.80 (m, 1 H), 3.87 - 4.04 (m, J=13.25, 6.85, 6.85, 6.70 Hz, 4 H), 3.52 - 3.64 (m, 2 H), 2.84 (q, J=6.91 Hz, 2 H), 1.17 - 1.38 (m, 6 H); Method 1, retention time: 6.181 min; HRMS: m/z (M+H)⁺ - 365.1858 (Calculated for C₂₂H₂5N₂0₃ = 365.1860).

[0263] NCGC00241441 (LLI02-025)

N-(3,4-diethoxyphenethyl)-5,6-dihydro-4H-cyclopenta[b]thiophene-2-carboxamide

Ή NMR (400 MHz, DMSO-c 6) δ ppm 8.33 (t, J=5.28 Hz, 1 H), 7.47 (s, 1 H), 6.84 (dd, J=8.22, 1.57 Hz, 1 H), 6.79 (s, 1 H), 6.69 (d, J=7.83 Hz, 1 H), 3.96 (qd, J=6.98, 1.37 Hz, 4 H), 3.39 (q, J=6.52 Hz, 2 H), 2.85 (t, J=7.04 Hz, 2 H), 2.63 - 2.76 (m, 4 H), 2.31 - 2.42 (m, J=7.29, 7.29, 7.14, 6.85 Hz, 2 H), 1.25 - 1.33 (m, 6 H); Method 1 , retention time: 5.998 min; HRMS: m/z (M+H)⁺ = 360.1633 (Calculated for C₂₀H₂₆NO₃S = 360.1628).

[0264] NCGC00241445 (LLI02-029)

N-(2-(benzo [d] [ 1 ,3] dioxol-5-yl)ethyl)-4-benzyl-4H-thieno [3,2-b]pyrrole-5-carboxamide

Ή NMR (400 MHz, DMSO-i/6) 5 ppm 8.31 (t, J=5.67 Hz, 1 H), 7.41 (d, J=5.09 Hz, 1 H), 7.17 - 7.31 (m, 3 H), 7.10 - 7.17 (m, 3 H), 7.07 (s, 1 H), 6.76 - 6.82 (m, 2 H), 6.64 (dd, J=8.02, 1.37 Hz, 1 H), 5.95 (s, 2 H), 5.78 (s, 2 H), 3.35 - 3.43 (m, 2 H), 2.72 (t, J=7.24 Hz, 2 H); Method 1, retention time: 6.318 min; HRMS: m/z (M+H)⁺ = 405.1277 (Calculated for

C₂₃H₂iN₂0₃S = 405.1267).

[0265] NCGC00034917 (LLI02-042)

Ethyl l-(l-(3-(2-chIorophenyl)ureido)cyclohexanecarbonyl)piperidine-4-carboxylate

Ή NMR (400 MHz, DMSO- 6) δ ppm 8.20 (s, 1 H), 8.05 (dd, J=8.31 , 0.88 Hz, 1 H), 7.39 (dd, J=8.02, 0.78 Hz, 1 H), 7.31 (s, 1 H), 7.16 - 7.24 (m, 1 H), 6.94 (td, J=7.68, 0.88 Hz, 1 H), 4.32 (d, J=13.30 Hz, 2 H), 3.98 (q, J=7.04 Hz, 2 H), 2.77 - 2.96 (m, 2 H), 2.51 - 2.57 (m, 1 H), 1.98 (d, J=13.50 Hz, 2 H), 1.63 - 1.82 (m, 4 H), 1.33 - 1.62 (m, 7 H), 1.14 - 1.27 (m, 1 H), 1.08 (t, J=7.04 Hz, 3 H); Method 1, retention time: 5.516 min; HRMS: m/z (M+H)⁺ = 436.2004 (Calculated for C₂₂H₃iClN₃0₄ = 436.1998).

[0266] NCGC00241446 (LLI02-044)

Ή NMR (400 MHz, DMSO- 6) δ ppm 8.08 (dd, J=8.22, 1.57 Hz, 1 H), 7.98 (br. s., 1 H), 7.79 (s, 1 H), 7.41 (dd, J=8.22, 1.17 Hz, 1 H), 7.24 (td, J=7.83, 1.57 Hz, 1 H), 6.98 (t, J=7.24 Hz, 1 H), 4.14 (d, J=13.30 Hz, 2 H), 4.04 (q, J=7.30 Hz, 2 H), 2.86 - 3.06 (m, 2 H), 2.54 - 2.64 (m, 1 H), 1.83 (dd, J=l 3.30, 2.74 Hz, 2 H), 1.36 - 1.51 (m, 2 H), 1.09 - 1.26 (m, 5 H), 0.94 (dd, J-2.93, 1.76 Hz, 2 H); Method 1 , retention time: 4.963 min; HRMS: m/z (M+H)⁺ = 394.1525 (Calculated for C_{I 9}H₂₅C1N₃0₄ - 394.1528).

[0267] NCGC00241447 (LLI02-045)

Ή NMR (400 MHz, DMSO- 6) δ ppm 8.05 (dd, J=8.61 , 1.57 Hz, 1 H), 7.91 (br. s., 1 H), 7.80 (s, 1 H), 7.39 (dd, 7=8.02, 1.37 Hz, 1 H), 7.21 (ddd, J=8.41 , 7.24, 1.57 Hz, 1 H), 6.91 - 6.99 (m, 1 H), 4.15 - 4.27 (m, 1 H), 4.00 (q, J=7.04 Hz, 2 H), 3.69 - 3.83 (m, 1 H), 2.93 - 3.08 (m, 2 H), 2.66 - 2.78 (m, 1 H), 2.51 - 2.61 (m, 2 H), 2.14 (br. s., 2 H), 1.83 - 1.96 (m, 1 H), 1.74 - 1.83 (m, 2 H), 1.63 - 1.72 (m, 1 H), 1.40 (br. s., 2 H), 1.07 - 1.13 (m, 3 H); Method 1 , retention time: 5.107 min; HRMS: m/z (M+H)⁺ = 408.1674 (Calculated for C₂₀H₂₇ClN₃O₄ = 408.1685).

[0268] NCGC00241448 (LLI02-047)

1H NMR (400 MHz, DMSO-i 6) δ ppm 8.06 (dd, J=8.61 , 1.57 Hz, 1 H), 7.92 (s, 1 H), 7.51 (s, 1 H), 7.38 (dd, 7=7.83, 1.57 Hz, 1 H), 7.21 (td, 7=7.92, 1.37 Hz, 1 H), 6.94 (td, J=7.63, 1.57 Hz, 1 H), 4.19 (d, J=12.13 Hz, 2 H), 3.98 (q, J=7.30 Hz, 2 H), 3.22 (dt, 7=12.62, 3.86 Hz, 1 H), 2.83 - 2.96 (m, 2 H), 2.50 - 2.59 (m, 2 H), 1.72 - 1.87 (m, 4 H), 1.55 - 1.71 (m, 4 H), 1.32 - 1.48 (m, 2 H), 1.08 (t, 7=7.04 Hz, 3 H); Method 1 , retention time: 5.290 min; HRMS: m/z (M+H)⁺ = 422.1833 (Calculated for C₂₁H₂₉C1N₃0₄ = 422.1841).

[0269] NCGC00241449 (LLI02-051)

Ethyl l-(2-(3-(2-chlorophenyl)ureido)acetyl)piperidine-4-carboxylate

Ή NMR (400 MHz, DMSO- 6) 5 ppm 8.42 (s, 1 H), 8.10 (dd, 7=8.41 , 1.37 Hz, 1 H), 7.39 (dd, 7=8.02, 1.37 Hz, 1 H), 7.28 (t, J=4.89 Hz, 1 H), 7.23 (td, 7=7.92, 1.37 Hz, 1 H), 6.91 - 6.99 (m, 1 H), 4.22 (d, J=12.91 Hz, 1 H), 4.08 (q, J=7.04 Hz, 2 H), 4.01 (t, J=4.70 Hz, 2 H), 3.73 (d, J=13.69 Hz, 1 H), 3.05 - 3.15 (m, 1 H), 2.74 - 2.84 (m, 1 H), 2.56 - 2.65 (m, 1 H), 1.85 (t, J=8.80 Hz, 2 H), 1.48 - 1.61 (m, 1 H), 1.40 (dd, J=13.1 1 , 3.33 Hz, 1 H), 1.19 (t, 3 H); Method 1, retention time: 4.862 min; HRMS: m/z (M+H)⁺ - 368.1377 (Calculated for Ci₇H₂₃ClN₃0₄ = 368.1372).

[0270] NCGC00241450 (LLI02-054)

Ethyl l-(2-(3-(2-chIorophenyl)ureido)-2-methylpropanoyl)piperidine-4-carboxylate

1H NMR (400 MHz, DMSO-i 6) 5 ppm 8.03 (dd, J=8.41 , 1.56 Hz, 1 H), 7.94 (s, 1 H), 7.42 (s, 1 H), 7.35 (dd, J=8.02, 1.37 Hz, 1 H), 7.18 (ddd, J=8.41, 7.24, 1.57 Hz, 1 H), 6.85 - 6.96 (m, 1 H), 4.28 (dt, J=13.16, 3.30 Hz, 2 H), 3.96 (q, J=7.17 Hz, 2 H), 2.76 - 2.99 (m, 2 H), 2.43 - 2.55 (m, 1 H), 1.73 (dd, J=13.11 , 2.93 Hz, 2 H), 1.31 - 1.45 (m, 8 H), 1.06 (t, J=7.14 Hz, 3 H); Method 1 , retention time: 4.995 min; HRMS: m/z (M+H)⁺ = 396.1676 (Calculated for Ci₉H₂₇ClN₃0₄ = 396.1685).

[0271] NCGC00241451 (LLI02-055)

N-(l-(2,4-difluorophenyl)-4,5,6,7-tetrahydro-lH-indazol-4-yl)-4-(3-(trifluoromethyl)- 3H-diazirin-3-yl)benzamide

Ή NMR (400 MHz, DMSO-i/6) δ ppm 8.84 (d, J=7.83 Hz, 1 H), 7.97 - 8.07 (m, 2 H), 7.51 - 7.64 (m, 3 H), 7.37 (d, J=8.22 Hz, 2 H), 7.21 - 7.32 (m, 1 H), 5.09 - 5.23 (m, 1 H), 2.45 - 2.58 (m, 2 H), 1.90 - 2.07 (m, 2 H), 1.66 - 1 .85 (m, 2 H); Method 1 , retention time: 6.409 min; HRMS: m/z (M+H)⁺ = 462.1340 (Calculated for C₂₂H,₇F₅N₅0 = 462.1348).

[0272] NCGC00241452 (LLI02-056)

N-(3,4-diethoxyphenethyl)-4-(3-(trifluoromethyl)-3H-diazirin-3-yl)benzamide

1H NMR (400 MHz, DMSO-t 6) δ ppm 8.65 (t, J-5.48 Hz, 1 H), 7.92 (d, J=8.61 Hz, 2 H), 7.38 (d, J=7.83 Hz, 2 H), 6.84 (d, J=8.22 Hz, 1 H), 6.79 (d, J=1.96 Hz, 1 H), 6.70 (dd, J=8.22, 1.96 Hz, 1 H), 3.95 (qd, J=6.98, 5.28 Hz, 4 H), 3.41 - 3.49 (m, 2 H), 2.75 (t, J-7.24 Hz, 2 H), 1.28 (q, J=7.04 Hz, 6 H); Method 1, retention time: 6.444 min; HRMS: m/z (M+Na)⁺ = 444.1485 (Calculated for C₂iH₂₂F₃N₃Na0₃ = 444.1505).

[0273] NCGC00241453 (LLI02-063)

4-Benzyl-N-(3,4-dihydroxyphenethyl)-4H-thieno[3,2-b]pyrrole-5-carboxamide

Ή NMR (400 MHz, DMSO- 6) δ ppm 8.73 (s, 1 H), 8.62 (s, 1 H), 8.31 (t, J=5.67 Hz, 1 H), 7.41 (d, J=5.48 Hz, 1 H), 7.24 - 7.30 (m, 2 H), 7.19 - 7.23 (m, 1 H), 7.12 - 7.17 (m, 3 H), 7.07 (s, 1 H), 6.60 - 6.64 (m, 2 H), 6.44 (dd, J=8.02, 2.15 Hz, 1 H), 5.78 (s, 2 H), 3.32 - 3.38 (m, 2 H), 2.58 - 2.65 (m, 2 H); Method 1, retention time: 5.440 min; HRMS: m/z (M+H)⁺ = 393.1263 (Calculated for C₂₂H₂iN₂0₃S = 393.1267).

[0274] NCGC00189556 (LLI02-071_2^nd_NEG)

(S)-N-(l-(2,4-difluorophenyl)-4,5,6,7-tetrahydro-lH-indazol-4-yl)picolinamide

Ή NMR (400 MHz, DMSO-c 6) δ ppm 8.53 - 8.68 (m, 2 H), 8.07 - 8.13 (m, 1 H), 8.02 (td, J=7.68, 1.66 Hz, 1 H), 7.53 - 7.66 (m, 4 H), 7.23 - 7.31 (m, 1 H), 5.12 - 5.20 (m, 1 H), 2.40 - 2.58 (m, 2 H), 1.72 - 2.02 (m, 4 H); Method 1, retention time: 5.150 min; HRMS: m/z (M+H)⁺ = 355.1367 (Calculated for C₁₉Hi₇F₂N₄0 = 355.1365).

[0275] NCGC00242548 (LLI02-073)

N-(l-(4-methoxyphenyl)-4,5,6,7-tetrahydro-lH-indazol-4-yl)picolinamide

1H NMR (400 MHz, DMSO- 6 ) δ ppm 8.60 - 8.64 (m, 1 H), 8.56 (d, J=8.22 Hz, 1 H), 8.07 - 8.12 (m, 1 H), 8.02 (td, J=7.63, 1.57 Hz, 1 H), 7.61 (ddd, J=7.53, 4.79, 1.37 Hz, 1 H), 7.51 (s, 1 H), 7.42 - 7.49 (m, 2 H), 7.02 - 7.08 (m, 2 H), 5.1 1 - 5.19 (m, 1 H), 3.81 (s, 3 H), 2.62 - 2.79 (m, 2 H), 1.72 - 2.02 (m, 4 H); Method 1 , retention time: 5.239 min; HRMS: m/z (M+H)⁺ = 349.1648 (Calculated for C₂oH₂iN₄0₂ = 349.1659).

[0276] NCGC00242549 (LLI02-081)

N-(l-(4-hydroxyphenyl)-4,5,6,7-tetrahydro-lH-indazol-4-yl)picolinamide

Ή NMR (400 MHz, DMSO-c/6) δ ppm 8.62 - 8.69 (m, 2 H), 8.12 - 8.18 (m, 1 H), 8.09 (t, J=7.63 Hz, 1 H), 7.66 (dd, J=7.04, 5.48 Hz, 1 H), 7.47 - 7.52 (m, 1 H), 7.28 - 7.36 (m, 2 H), 6.80 - 6.94 (m, 3 H), 5.10 - 5.21 (m, 1 H), 2.57 - 2.77 (m, 2 H), 1.68 - 2.05 (m, 4 H); Method 1 , retention time: 4.493 min; HRMS: m/z (M+H)⁺ = 335.1501 (Calculated for C|₉H₁₉N₄0₂ = 335.1503).

[0277] NCGC00242550 (LLI02-085)

l-(2-(3-(2-Chlorophenyl)ureido)-2-methylpropanoyl)piperidine-4-carboxylic acid

1H NMR (400 MHz, DMSO- 6) δ ppm 12.20 (s, 1 H), 8.07 (dd, J=8.22, 1.56 Hz, 1 H), 7.97 (s, 1 H), 7.47 (d, J=16.82 Hz, 1 H), 7.39 (dd, J=8.02, 1.37 Hz, 1 H), 7.17 - 7.25 (m, 1 H), 6.90 - 6.98 (m, 1 H), 4.29 (d, J=13.30 Hz, 2 H), 2.82 - 2.98 (m, 2 H), 2.44 (tt, J=10.91, 4.16 Hz, 1 H), 1.76 (dd, J=13.11 , 2.93 Hz, 2 H), 1.33 - 1.48 (m, 8 H); Method 1 , retention time: 4.109 min; HRMS: m/z (M+H)⁺ = 368.1366 (Calculated for C_I7H₂₃C1N₃0₄ = 368.1372).

[0278] NCGC00242551 (LLI02-091)

feri-Butyl 2-(2-(2-(4-(4-(picolinamido)-4,5,6,7-tetrahydro-lH-indazol-l- yl)phenoxy)ethoxy)ethoxy)ethylcarbamate

Ή NMR (400 MHz, CHLOROFORM-d) δ ppm 8.53 (ddd, J=4.79, 1.56, 0.88 Hz, 1 H), 8.26 (dt, J=7.83, 0.98 Hz, 2 H), 7.88 (td, J=7.78, 1.66 Hz, 2 H), 7.63 (s, 1 H), 7.53 (s, 1 H), 7.40 (d, J=9.00 Hz, 2 H), 6.98 - 7.05 (m, 2 H), 5.30 - 5.41 (m, 1 H), 4.19 (dd, J=5.48, 4.1 1 Hz, 2 H), 3.90 (dd, J=5.28, 4.1 1 Hz, 2 H), 3.71 - 3.77 (m, 2 H), 3.64 - 3.71 (m, 2 H), 3.54 - 3.61 (m, 2 H), 3.34 (ddd, J=4.45, 2.01 , 1.17 Hz, 2 H), 2.67 - 2.76 (m, 2 H), 1.93 (br. s., 2 H), 1.22 - 1.33 (m, 9 H), 0.89 (br. s., 2 H); Method 1 , retention time: 5.694 min; HRMS: m/z (M+H)⁺ = 566.2963 (Calculated for C₃oH4oN₅0₆ = 566.2973).

[0279] NCGC00242552 (LLI02-098)

Ή NMR (400 MHz, DMSO- 6) δ ppm 8.33 (s, 1 H), 7.06 - 7.13 (m, 2 H), 6.76 - 6.80 (m, 1 H), 6.62 (s, 1 H), 6.44 - 6.48 (m, 1 H), 4.32 (d, J=12.91 Hz, 2 H), 4.00 (q, J=7.04 Hz, 2 H), 3.67 - 3.71 (m, 3 H), 3.21 (dt, J=12.52, 3.91 Hz, 1 H), 2.88 (td, J=12.13, 3.13 Hz, 2 H), 1.76 (dd, J=12.91 , 2.74 Hz, 2 H), 1.35 - 1.48 (m, 8 H), 1.10 (t, J=7.24 Hz, 3 H); Method 1, retention time: 4.654 min; HRMS: m/z (M+H)⁺ = 392.2176 (Calculated for C₂₀H₃oN₃0₅ = 392.2180).

[0280] NCGC00242553 (LLI03-001)

Ethyl l-(2-(3-(3,4-difluorophenyl)ureido)-2-methyIpropanoyl)piperidine-4-carboxylate

Ή NMR (400 MHz, DMSO- 6) δ ppm 8.57 (s, 1 H), 7.56 (ddd, J=13.65, 7.48, 2.54 Hz, 1 H), 7.26 (dt, J=l 0.61 , 9.17 Hz, 1 H), 6.97 (dddd, J=9.02, 3.99, 2.54, 1.66 Hz, 1 H), 6.75 (s, 1 H), 4.31 (dt, J=13.21, 2.98 Hz, 2 H), 4.00 (q, J=7.11 Hz, 2 H), 2.77 - 3.02 (m, 2 H), 2.50 - 2.59 (m, 1 H), 1.70 - 1.82 (m, 2 H), 1.33 - 1.47 (m, 8 H), 1.10 (t, J=7.14 Hz, 3 H); Method 1 , retention time: 4.934 min; HRMS: m/z (M+H)⁺ = 398.1873 (Calculated for Ci₉H₂₆F₂N₃0₄ = 398.1886

[0281] NCGC00242554 (LLI03-002)

Ethyl l-(2-(3-(2,3-dihydro-lH-inden-5-yl)ureido)-2-methylpropanoyl)piperidine-4- carboxylate

Ή NMR (400 MHz, DMSO-i 6) δ ppm 8.16 (s, 1 H), 7.27 (s, 1 H), 6.95 - 7.07 (m, 2 H), 6.54 (s, 1 H), 4.32 (d, J=13.1 1 Hz, 2 H), 4.00 (q, J=7.04 Hz, 2 H), 3.25 (dt, J=12.67, 3.55 Hz, 1 H), 2.92 (td, J=12.42, 3.13 Hz, 2 H), 2.76 (ddd, J=10.42, 7.48, 7.34 Hz, 4 H), 1.97 (quin, J=7.39 Hz, 2 H), 1.72 - 1 .80 (m, 2 H), 1.34 - 1 .48 (m, 8 H), 1.10 (t, J=7.14 Hz, 3 H); Method 1 , retention time: 5.247 min; HRMS: m/z (M+H)⁺ = 402.2380 (Calculated for C₂₂H₃2N₃04 = 402.2387).

[0282] NCGC00242555 (LLI03-003)

Ή NMR (400 MHz, DMSO- 6) δ ppm 8.35 (s, 1 H), 7.29 - 7.40 (m, 4 H), 7.03 - 7.10 (m, 1 H), 6.85 - 6.96 (m, 4 H), 6.61 (s, 1 H), 4.33 (d, J=12.91Hz, 2 H), 4.01 (q, J=7.04 Hz, 2 H), 2.82 - 2.96 (m, 2 H), 2.51 - 2.58 (m, 1 H), 1.77 (dd, J=13.1 1 , 3.33 Hz, 2 H), 1.34 - 1.50 (m, 8 H), 1.1 1 (t, J=7.24 Hz, 3 H); Method 1, retention time: 5.531 min; HRMS: m/z (M+H)⁺ = 454.2339 (Calculated for C₂₅H₃₂N₃0₅ = 454.2336).

[0283] NCGC00242556 (LLI03-004)

Ethyl 1 -(2-(3-(2-chloro-4-(trifluoromethyl)phenyl)ureido)-2- methylpropanoyl)piperidine-4-carboxylate

Ή NMR (400 MHz, DMSO-d6) δ ppm 8.33 (d, J=8.80 Hz, 1 H), 8.29 (s, 1 H), 7.77 (d, J=1.57 Hz, 1 H), 7.67 (s, 1 H), 7.56 (dd, J=9.00, 1.96 Hz, 1 H), 4.18 - 4.33 (m, 2 H), 3.94 (q, J=7.04 Hz, 2 H), 2.71 - 3.02 (m, 2 H), 2.39 - 2.56 (m, 1 H), 1.73 (dd, J=13.01 , 2.64 Hz, 2 H), 1.26 - 1.44 (m, 8 H), 1.02 (t, J=7.14 Hz, 3 H); Method 1 , retention time: 5.748 min; HRMS: m/z (M+H)⁺ = 464.1561 (Calculated for C₂₀H₂₆ClF₃N₃O₄ = 464.1558).

[0284] NCGC00242559 (LLI03-008)

1H NMR (400 MHz, DMSO- 6) 6 ppm 8.31 (s, 1 H), 7.55 (d, J=2.35 Hz, 1 Η), 7.09 - 7.15 (m, 1 H), 7.01 (d, J=9.00 Hz, 1 H), 6.63 (s, 1 H), 4.32 (d, J=13.30 Hz, 2 H), 4.00 (q, J=7.04 Hz, 2 H), 3.77 (s, 3 H), 3.20 - 3.29 (m, 1 H), 2.92 (td, J=12.33, 3.13 Hz, 2 H), 1.76 (dd, J=13.11 , 2.93 Hz, 2 H), 1.34 - 1.48 (m, 8 H), 1.10 (t, J=7.04 Hz, 3 H); Method p retention time: 4.880 min; HRMS: m/z (M+H)⁺ = 426.1798 (Calculated for C₂oH₂9ClN₃0₅ =

426.1790).

[0285] NCGC00242560 (LLI03-009)

Ethyl l-(2-(3-(2,4-dichlorophenyl)ureido)-2-methylpropanoyl)piperidine-4-carboxylate

1H NMR (400 MHz, DMSO-^6) δ ppm 8.1 1 (d, J=9.00 Hz, 1 H), 8.07 (s, 1 H), 7.55 (d, J=2.35 Hz, 1 H), 7.50 (s, 1 H), 7.30 (dd, J=9.00, 2.74 Hz, 1 H), 4.29 (d, J=13.30 Hz, 2 H), 3.99 (q, J=7.04 Hz, 2 H), 2.84 - 2.97 (m, 2 H), 2.51 - 2.57 (m, 1 H), 1.76 (dd, J=13.30, 3.13 Hz, 2 H), 1.32 - 1.45 (m, 8 H), 1.09 (t, J=7.04 Hz, 3 H); Method 1 , retention time: 5.494 min; HRMS: m/z (M+H)⁺ = 430.1287 (Calculated for Ci₉H₂₆Cl₂N₃0₄ = 430.1295).

[0286] NCGC00242565 (LLI03-019)

Ethyl l-(2-(3-(4-cyanophenyl)ureido)-2-methylpropanoyl)piperidine-4-carboxylate

1H NMR (400 MHz, DMSO-i 6) δ ppm 8.89 (s, 1 H), 7.65 (d, J=9.00 Hz, 2 H), 7.51 (d, J=9.00 Hz, 2 H), 6.90 (s, 1 H), 4.30 (d, J=13.30 Hz, 2 H), 3.99 (q, J=7.17 Hz, 2 H), 2.79 - 2.99 (m, 2 H), 2.51 - 2.59 (m, 1 H), 1.76 (dd, J=l 2.91 , 2.74 Hz, 2 H), 1.30 - 1.48 (m, 8 H), 1.09 (t, J=7.24 Hz, 3 H); Method 1 , retention time: 4.569 min; HRMS: m/z (M+H)⁺ = 387.2010 (Calculated for C₂₀H₂₇N₄O₄ = 387.2027).

[0287] NCGC00242566 (LLI03-021 )

Ethyl l-(2-methyl-2-(3-naphthalen-2-ylureido)propanoyl)piperidine-4-carboxylate

Ή NMR (400 MHz, DMSO- 6) δ ppm 8.55 (s, 1 H), 7.99 (d, J=1.96 Hz, 1 H), 7.69 - 7.79 (m, 3 H), 7.35 - 7.44 (m, 2 H), 7.28 - 7.34 (m, 1 H), 6.73 (s, 1 H), 4.35 (d, J=13.30 Hz, 2 H), 3.94 (q, J=7.04 Hz, 2 H), 2.83 - 3.00 (m, 2 H), 2.52 - 2.58 (m, 1 H), 1.72 - 1.83 (m, 2 H), 1.38 - 1.51 (m, 8 H), 1.02 (t, J=7.04 Hz, 3 H); Method 1 , retention time: 5.223 min; HRMS: m/z (M+H)⁺ = 412.2224 (Calculated for C₂₃H₃₀N₃O₄ = 412.2231).

[0288] NCGC00242567 (LLI03-022)

Ethyl 1 -(2-(3-benzo [b] thiophen-5-ylureido)-2-methylpropanoyl)piperidine-4- carboxylate

1H NMR (400 MHz, DMSO- 6) δ ppm 8.41 (s, 1 H), 7.99 (d, J=1.96 Hz, 1 H), 7.80 (d, J=8.61 Hz, 1 H), 7.68 (d, J-5.09 Hz, 1 H), 7.32 (d, J=5.48 Hz, 1 H), 7.23 (dd, J=8.61 , 1.96 Hz, 1 H), 6.65 (s, 1 H), 4.34 (d, J=13.30 Hz, 2 H), 3.96 (q, J=7.17 Hz, 2 H), 2.80 - 3.01 (m, 2 H), 2.51 - 2.58 (m, 1 H), 1.77 (dd, J=l 3.11, 2.93 Hz, 2 H), 1.37 - 1.51 (m, 8 H), 1.05 (t, J=7.04 Hz, 3 H); Method 1 , retention time: 5.078 min; HRMS: m/z (M+H)⁺ = 418.1783 (Calculated for C₂iH₂₈N₃0₄S = 418.1795).

[0289] NCGC00242568 (LLI03-023)

Ethyl l-(2-(3-biphenyl-4-ylureido)-2-methylpropanoyl)piperidine-4-carboxylate

Ή NMR (400 MHz, DMSO- 6) δ ppm 8.44 (s, 1 H), 7.60 (dd, J=8.41 , 1.37 Hz, 2 H), 7.50 - 7.55 (m, 2 H), 7.38 - 7.47 (m, 4 H), 7.26 - 7.32 (m, 1 H), 6.67 (s, 1 H), 4.34 (d, J=13.30 Hz, 2 H), 3.99 (q, J=7.30 Hz, 2 H), 2.81 - 3.01 (m, 2 H), 2.51 - 2.58 (m, 1 H), 1.77 (dd, J-12.91 , 2.74 Hz, 2 H), 1.35 - 1.50 (m, 8 H), 1.08 (t, J=7.04 Hz, 3 H); Method 1 , retention time: 5.538 min; HRMS: m/z (M+H)⁺ = 438.2395 (Calculated for C25H32N3O4 = 438.2387).

[0290] NCGC00242569 (LLI03-026)

Ethyl l-(2-methyl-2-(3-(4-nitrophenyl)ureido)propanoyl)piperidine-4-carboxylate

Ή NMR (400 MHz, DMSCW6) δ ppm 9.17 (s, 1 H), 8.09 - 8.16 (m, 2 H), 7.54 - 7.61 (m, 2 H), 7.01 (s, 1 H), 4.29 (d, J=13.30 Hz, 2 H), 3.99 (q, J=7.04 Hz, 2 H), 2.90 (br. s., 2 H), 2.52 - 2.58 (m, 1 H), 1.76 (dd, J=13.1 1, 2.93 Hz, 2 H), 1.32 - 1.47 (m, 8 H), 1.08 (t, 3 H); Method 1, retention time: 4.818 min; HRMS: m/z (M+H)⁺ = 407.1928 (Calculated for Ci₉H₂₇N₄0₆ = 407.1925).

[0291] NCGC00242571 (LLI03-036)

N-(l-(2-hydroxyethyl)-4,5,6,7-tetrahydro-lH-indazol-4-yl)picolinamide

1H NMR (400 MHz, CHLOROFORM-d) δ ppm 8.51 (ddd, J=4.84, 1.71 , 0.88 Hz, 1 H), 8.24 (dt, J=7.83, 1.08 Hz, 1 H), 8.17 (d, J=7.43 Hz, 1 H), 7.87 (td, J=7.73, 1.76 Hz, 1 H), 7.48 (s, 1 H), 7.43 (ddd, J=7.58, 4.84, 1.27 Hz, 1 H), 5.23 - 5.30 (m, 1 H), 4.09 - 4.15 (m, 1 H), 3.99 - 4.05 (m, 2 H), 2.56 - 2.73 (m, 2 H), 2.06 - 2.15 (m, 2 H), 1.82 - 2.06 (m, 4 H); Method 1 , retention time: 3.516 min; HRMS: m/z (M+H)⁺ = 287.1515 (Calculated for Ci₅H₁₉N₄0₂ = 287.1503).

[0292] NCGC00242572 (LLI03-037)

tert-Butyl 2-(2-(2-(2-(4-(picolinamido)-4,5,6,7-tetrahydro-lH-indazol-l- yl)ethoxy)ethoxy)ethoxy)ethylcarbamate

Ή NMR (400 MHz, CHLOROFORM-c ) 6 ppm 8.44 - 8.58 (m, 1 H), 8.24 (d, J=7.83 Hz, 1 H), 8.16 (d, J=8.02 Hz, 1 H), 7.86 (td, J=7.73, 1.17 Hz, 1 H), 7.36 - 7.53 (m, 2 H), 5.20 - 5.29 (m, 1 H), 5.04 - 5.13 (m, 1 H), 4.16 - 4.25 (m, 2 H), 3.80 - 3.89 (m, 2 H), 3.50 - 3.63 (m, 8 H), 3.27 - 3.36 (m, 2 H), 2.62 - 2.75 (m, 2 H), 2.04 - 2.15 (m, 2 H), 1.78 - 2.03 (m, 4 H), 1.38 - 1.50 (m, 9 H); Method 1, retention time: 4.956 min; HRMS: m/z (M+H)⁺ = 518.2970 (Calculated for C₂6H₄oN₅0₆ = 518.2973).

[0293] NCGC00242573 (LLI03-044)

N-(l-(3-methoxyphenyl)-4,5,6,7-tetrahydro-lH-indazol-4-yl)picolinamide

1H NMR (400 MHz, DMSO-i/6) δ ppm 8.60 - 8.63 (m, 1 H), 8.59 (d, J=8.22 Hz, 1 H), 8.08 - 8.12 (m, 1 H), 8.00 - 8.05 (m, 1 H), 7.61 (ddd, J=7.53, 4.79, 1.37 Hz, 1 H), 7.56 (s, 1 H), 7.41 (t, J=8.22 Hz, 1 H), 7.09 - 7.15 (m, 2 H), 6.93 - 6.98 (m, 1 H), 5.12 - 5.19 (m, 1 H), 3.81 (s, 3 H), 2.79 (dt, J=\ 1.84, 6.02 Hz, 2 H), 1.77 - 2.01 (m, 4 H); Method 1 , retention time: 5.454 min; HRMS: m/z (M+H)⁺ = 349.1665 (Calculated for C₂₀H₂iN₄O₂ = 349.1659).

[0294] NCGC00242574 (LLI03-047)

OH N-(l-(3-hydroxyphenyl)-4,5,6,7-tetrahydro-lH-indazol-4-yl)picolinamide

Ή NMR (400 MHz, DMSO- 6) δ ppm 9.77 (br. s., 1 Η), 8.53 - 8.67 (m, 2 H), 8.07 - 8.14 (m, 1 H), 8.02 (td, J=7.68, 1.66 Hz, 1 H), 7.61 (ddd, J=7.58, 4.74, 1.37 Hz, 1 H), 7.53 (s, 1 H), 7.28 (t, J=8.31 Hz, 1 H), 6.93 - 7.01 (m, 2 H), 6.76 (ddd, J=8.22, 2.35, 0.98 Hz, 1 H), 5.09 - 5.20 (m, 1 H), 2.68 - 2.86 (m, 2 H), 1.71 - 2.04 (m, 4 H); Method 1 , retention time: 4.686 min; HRMS: m/z (M+Na)⁺ = 357.1331 (Calculated for Ci₉H₁₈N Na0₂ = 357.1322).

[0295] NCGC00242575 (LLI03-050)

fert-Butyl 2-(2-(2-(3-(4-(picolinamido)-4,5,6,7-tetrahydro-lH-indazol-l- yl)phenoxy)ethoxy)ethoxy)ethylcarbamate

Ή NMR (400 MHz, DMSO-c/6) δ ppm 8.53 - 8.66 (m, 2 H), 8.07 - 8.14 (m, 1 H), 7.97 - 8.07 (m, 1 H), 7.61 (ddd, J=7.53, 4.79, 1.37 Hz, 1 H), 7.55 (s, 1 H), 7.40 (t, J=8.22 Hz, 1 H), 7.07 - 7.18 (m, 2 H), 6.93 - 6.99 (m, 1 H), 6.71 - 6.78 (m, 1 H), 5.09 - 5.21 (m, 1 H), 4.1 1 - 4.19 (m, 2 H), 3.72 - 3.82 (m, 2 H), 3.56 - 3.62 (m, 2 H), 3.49 - 3.56 (m, 2 H), 3.06 (q, J=5.93 Hz, 2 H), 2.80 (dd, J=l 1.84, 6.55 Hz, 2 H), 1.97 (ddd, J=3.42, 2.45, 0.78 Hz, 6 H), 1.36 (s, 9 H); Method 1 , retention time: 5.902 min; HRMS: m/z (M+H)⁺ = 566.2984 (Calculated for C₃oH4oN₅0₆ = 566.2973).

[0296] NCGC00242563 (LLI03-065)

l-(2-(3-(2-Chlorophenyl)ureido)-2-methylpropanoyl)-N-ethylpiperidine-4-carboxamide

Ή NMR (400 MHz, DMSO-c 6) δ ppm 8.09 (dd, J=8.22, 1.57 Hz, 1 H), 7.95 (s, 1 H), 7.69 (t, j=5.48 Hz, 1 H), 7.44 (s, 1 H), 7.39 (dd, J=8.02, 1.37 Hz, 1 H), 7.18 - 7.25 (m, 1 H), 6.94 (td, J=7.63, 1.57 Hz, 1 H), 4.40 (d, J=13.30 Hz, 2 H), 2.96 - 3.05 (m, 2 H), 2.69 - 2.84 (m, 2 H), 2.20 - 2.30 (m, J=l 1.25, 11.25, 3.91 , 3.72 Hz, 1 H), 1.63 (dd, J=12.52, 2.35 Hz, 2 H), 1.34 - 1.48 (m, 8 H), 0.95 (t, J=7.24 Hz, 3 H); Method 1 , retention time: 4.206 min; HRMS: m/z (M+H)⁺ = 395.1843 (Calculated for C₁₉H₂₈C1N₄0₃ = 395.1844).

[0297] NCGC00242564 (LLI03-066)

l-(2-(3-(2-Chlorophenyl)ureido)-2-methylpropanoyl)-N,N-diethylpiperidine-4- carboxamide

Ή NMR (400 MHz, DMSO- 6) δ ppm 8.10 (dd, J=8.41 , 1.37 Hz, 1 H), 7.95 (s, 1 H), 7.45 (s, 1 H), 7.38 (dd, J=8.02, 1.37 Hz, 1 H), 7.22 (ddd, J=8.41, 7.24, 1.57 Hz, 1 H), 6.91 - 6.97 (m, 1 H), 4.44 (d, J=12.91 Hz, 2 H), 3.26 - 3.38 (m, 2 H), 3.20 (q, J=7.04 Hz, 2 H), 2.76 - 3.02 (m, 2 H), 2.65 - 2.76 (m, 1 H), 1.33 - 1.64 (m, 10 H), 1.09 (t, J=7.04 Hz, 3 H), 0.95 (t, J=7.04 Hz, 3 H); Method 1, retention time: 4.810 min; HRMS: m/z (M+H)⁺ = 423.2150 (Calculated for C₂iH₃₂ClN₄0₃ = 423.2157).

[0298] NCGC00244462 (LLI03-089)

Ή NMR (400 MHz, DMSO- 6) δ ppm 8.57 - 8.63 (m, 1 H), 8.53 (d, J=8.22 Hz, 1 H), 8.04 - 8.1 1 (m, 1 H), 7.99 (td, J=7.63, 1.57 Hz, 1 H), 7.79 (t, J=5.67 Hz, 1 H), 7.58 (ddd, J=7.53, 4.79, 1.37 Hz, 1 H), 7.48 (s, 1 H), 7.39 - 7.45 (m, 2 H), 6.99 - 7.08 (m, 2 H), 6.37 (br. s., 1 H), 5.07 - 5.17 (m, 2 H), 4.26 (dd, J=7.63, 4.50 Hz, 1 H), 4.04 - 4.15 (m, 3 H), 3.74 (dd, J=5.48, 3.91 Hz, 2 H), 3.54 - 3.63 (m, 2 H), 3.38 (t, J=5.87 Hz, 2 H), 3.12 - 3.21 (m, 2 H), 3.05 (ddd, J=8.41 , 6.26, 4.50 Hz, 1 H), 2.78 (dd, J=12.33, 5.28 Hz, 1 H), 2.60 - 2.72 (m, 2 H), 2.54 (d, J=12.52 Hz, 1 H), 2.03 (t, J=7.43 Hz, 2 H), 1.70 - 1.99 (m, 4 H), 1.35 - 1.64 (m, 5 H), 1.16 - 1.34 (m, 3 H); Method 1 , retention time: 4.669 min; HRMS: m/z (M+H)⁺ = 692.3225 (Calculated for C₃5H₄6N₇0₆S = 692.3225).

[0299] NCGC00244959 (LLI03-093)

2-(Dimethylamino)-N-(l-(4-methoxyphenyl)-4,5,6,7-tetrahydro-lH-indazol-4- yl)acetamide

Ή NMR (400 MHz, DMSO-i 6) δ ppm 8.83 (d, J=7.83 Hz, 1 H), 7.51 - 7.54 (m, 1 H), 7.40 - 7.45 (m, 2 H), 7.03 - 7.07 (m, 2 H), 4.94 - 5.00 (m, 1 H), 3.89 (d, J=1.57 Hz, 2 H), 3.81 (s, 3 H), 2.81 - 2.85 (m, 6 H), 2.68 (t, J=5.87 Hz, 2 H), 1.74 - 1.94 (m, 3 H), 1.63 - 1.71 (m, 1 H); Method 1 , retention time: 3.561 min; HRMS: m/z (M+H)⁺ = 329.1980 (Calculated for C₁₈H₂₅N₄02 = 329.1972).

[0300] NCGC00244960 (LLI04-001)

(S)-Ethyl l-(3-(benzyloxy)-2-(3-(2-chlorophenyl)ureido)propanoyl)piperidine-4- carboxylate

1H NMR (400 MHz, DMSO-i 6) δ ppm 8.37 (d, J=8.22 Hz, 1 H), 8.08 (td, J=8.41 , 1.57 Hz, 1 H), 7.54 (d, J=8.61 Hz, 1 H), 7.19 - 7.42 (m, 7 H), 6.96 (td, J=7.63, 1.57 Hz, 1 H), 4.95 (dt, J=8.22, 5.87 Hz, 1 H), 4.44 - 4.57 (m, 2 H), 4.25 (t, J=12.52 Hz, 1 H), 4.06 (q, J=7.04 Hz, 2 H), 3.88 -3.99 (m, 1 H), 3.56 (d, J=5.48 Hz, 2 H), 3.07 - 3.20 (m, 1 H), 2.72 - 2.86 (m, 1 H), 2.59 (br. s., 1 H), 1.75 - 1.89 (m, 2 H), 1.32 - 1.45 (m, 2 H), 1.17 (t, J=7.04 Hz, 3 H); Method 1 , retention time: 6.137 min; HR.MS: m/z (M+H)⁺ = 488.1954 (Calculated for C2₅H3₁CIN3O5 = 488.1947).

[0301] NCGC00244961 (LLI04-002)

Ή NMR (400 MHz, DMSO- 6) δ ppm 8.37 (d, J=8.22 Hz, 1 H), 8.04 - 8.13 (m, 1 H), 7.54 (d, J=8.22 Hz, 1 H), 7.18 - 7.42 (m, 7 H), 6.96 (td, J=7.63, 1.57 Hz, 1 H), 4.95 (ddd, J=8.41 , 5.87, 5.67 Hz, 1 H), 4.44 - 4.57 (m, 2 H), 4.25 (t, J=13.30 Hz, 1 H), 4.06 (q, J=7.04 Hz, 2 H), 3.87 - 3.99 (m, 1 H), 3.56 (d, J=5.48 Hz, 2 H), 3.05 - 3.21 (m, 1 H), 2.72 - 2.86 (m, 1 H), 2.53 - 2.64 (m, 1 H), 1.75 - 1.89 (m, 2 H), 1.32 - 1.45 (m, 2 H), 1.17 (t, J=7.04 Hz, 3 H); Method 1 , retention time: 6.145 min; HRMS: m/z (M+H)⁺ = 488.1942 (Calculated for C₂₅H₃iClN₃0₅ = 488.1947).

[0302] NCGC00244963 (LLI04-032)

N-(l-(4-methoxyphenyl)-4,5,6,7-tetrahydro-lH-indazol-4-yl)quinoline-6-carboxamide

Ή NMR (400 MHz, DMSO-t/6) δ ppm 9.05 (dd, J=4.50, 1.76 Hz, 1 H), 8.92 (d, J=7.83 Hz, 1 H), 8.63 (d, J=1.96 Hz, 1 H), 8.59 (dd, J=8.61 , 0.78 Hz, 1 H), 8.29 (dd, J=8.61 , 1.96 Hz, 1 H), 8.1 1 (d, J=9.00 Hz, 1 H), 7.70 (dd, J=8.22, 4.30 Hz, 1 H), 7.58 (s, 1 H), 7.44 - 7.49 (m, 2 H), 7.03 - 7.09 (m, 2 H), 5.20 - 5.26 (m, 1 H), 3.81 (s, 3 H), 2.73 (br. s., 2 H), 1.98 - 2.05 (m, 2 H), 1.82 (dd, 2 H); Method 1 , retention time: 4.179 min; HRMS: m/z (M+H)⁺ = 399.1815 (Calculated for C₂₄H23N₄02 = 399.1816).

[0303] NCGC00244965 (LLI04-051)

N-(l-(4-(2-(2-(2-(5-(l-(7-hydroxy-2-oxo-2H-chromen-3-yl)-lH-l,2,3-triazol-4- yl)pentanamido)ethoxy)ethoxy)ethoxy)phenyl)-4,5,6,7-tetrahydro-lH-indazol-4- yl)picolinamide

Ή NMR (400 MHz, CHLOROFORM-cf) δ ppm 8.54 (d, J=3.72 Hz, 1 H), 8.35 (s, 1 H), 8.22 - 8.32 (m, 2 H), 7.84 - 7.95 (m, 1 H), 7.67 (br. s., 1 H), 7.41 - 7.49 (m, 1 H), 7.34 (d, J=8.61 Hz, 2 H), 6.92 (d, J=8.02 Hz, 2 H), 6.75 (d, J=8.22 Hz, 1 H), 6.58 (br. s., 1 H), 6.29 (br. s., 1 H), 5.31 - 5.40 (m, 1 H), 4.04 - 4.16 (m, 2 H), 3.83 (td, J=3.72, 0.98 Hz, 2 H), 3.66 (ddd, J=15.11 , 3.77, 1.86 Hz, 4 H), 3.54 - 3.61 (m, 2 H), 3.42 - 3.53 (m, 2 H), 2.79 - 2.88 (m, 3 H), 2.61 - 2.75 (m, 3 H), 2.26 (ddd, J=7.04, 4.89, 2.54 Hz, 2 H), 2.13 - 2.22 (m, 1 H), 1.87 - 2.05 (m, 4 H), 1.65 - 1.83 (m, 4 H); Method 1 , retention time: 5.170 min; HRMS: m/z (M+H)⁺ = 777.3362 (Calculated for C₄iH₄₅N₈0₈ = 777.3355).

[0304] NCGC00244966 (LLI04-052)

N-(l-(4-(2-(2-(2-(2-(l-(7-hydroxy-2-oxo-2H-chromen-3-yl)-lH-l,2,3-triazol-4- yl)ethylamino)ethoxy)ethoxy)ethoxy)phenyl)-4,5,6,7-tetrahydro-lH-indazol-4- yl)picolinamide Ή NMR (400 MHz, DMSO-t 6) 5 ppm 10.94 (s, 1 H), 8.59 - 8.69 (m, 3 H), 8.57 (s, 1 H), 8.55 (d, J=8.22 Hz, 1 H), 8.49 (s, 1 H), 8.07 - 8.13 (m, 1 H), 7.99 - 8.06 (m, 1 H), 7.75 (d, J=8.61 Hz, 1 H), 7.61 (ddd, J-7.53, 4.79, 1.37 Hz, 1 H), 7.50 (s, 1 H), 7.41 - 7.46 (m, 2 H), 7.02 - 7.08 (m, 2 H), 6.91 (dd, J=8.61 , 2.35 Hz, 1 H), 6.85 (d, J=2.35 Hz, 1 H), 5.10 - 5.19 (m, 1 H), 4.15 (dd, J=5.48, 3.52 Hz, 2 H), 3.76 - 3.81 (m, 2 H), 3.69 - 3.74 (m, 2 H), 3.61 - 3.69 (m, 4 H), 3.18 - 3.26 (m, 2 H), 3.08 - 3.15 (m, 2 H), 2.65 - 2.72 (m, 2 H), 1.73 - 2.00 (m, 5 H); Method 1, retention time: 4.328 min; HRMS: m/z (M+H)⁺ - 721.3090 (Calculated for C₃₈H₄₁N₈0₇ = 721.3093).

253 (LLI04-078)

N-(l-(4-hydroxyphenyl)-4,5,6,7-tetrahydro-lH-indazol-4-yl)-2-(5,6,7,8- tetrahydronaphthalen-2-yl)acetamide

Ή NMR (400 MHz, DMSO-J6) δ ppm 9.69 (s, 1 H), 8.28 (d, J=7.83 Hz, 1 H), 7.37 (s, 1 H), 7.25 - 7.32 (m, 2 H), 6.92 - 6.99 (m, 3 H), 6.81 - 6.88 (m, 2 H), 4.80 - 4.89 (m, 1 H), 3.37 (br. s., 3 H), 2.57 - 2.75 (m, 6 H), 1.84 (ddd, J=7.63, 4.11, 3.91 Hz, 2 H), 1.72 (dt, J=6.36, 3.28 Hz, 4 H), 1.53 - 1.63 (m, 1 H); Method 1 , retention time: 5.559 min; HRMS: m/z (M+H)⁺ = 402.2159 (Calculated for C25H28N3O2 = 402.2176).

264 (LLI04-079)

N-(2-(l-(4-hydroxyphenyl)-4,5,6,7-tetrahydro-lH-indazol-4-ylamino)-2- oxoethyl)benzamide

Ή NMR (400 MHz, DMSO-c 6) 6 ppm 9.69 (br. s., 1 H), 8.67 (t, J=5.87 Hz, 1 H), 8.18 (d, J=7.83 Hz, 1 H), 7.89 (d, J=7.04 Hz, 2 H), 7.42 - 7.58 (m, 4 H), 7.24 - 7.32 (m, 2 H), 6.81 - 6.88 (m, 2 H), 4.87 - 4.96 (m, 1 H), 3.89 (d, J=5.87 Hz, 2 H), 2.63 (t, J=5.28 Hz, 2 H), 1.87 (dd, J=9.39, 4.70 Hz, 2 H), 1.67 - 1.78 (m, 1 H), 1.57 - 1.67 (m, 1 H); Method 1 , retention time: 4.128 min; HRMS: m/z (M+H)⁺ = 391.1748 (Calculated for C₂₂H23N₄03 = 391.1765).

LLI06-030)

(S)-ethyl l-(2-(3-(2-chlorophenyl)ureido)propanoyl)piperidine-4-carboxylate

Ή NMR (400 MHz, DMSO- 6) 5 ppm 8.26 (br. s., 1 H), 8.1 1 (d, J=8.22 Hz, 1 H), 7.45 (d, J=7.83 Hz, 1 H), 7.39 (d, J=7.83 Hz, 1 H), 7.22 (t, J=7.63 Hz, 1 H), 6.95 (t, J=7.63 Hz, 1 H), 4.71 (qd, J=6.91, 6.65 Hz, 1 H), 4.15 - 4.31 (m, 1 H), 4.07 (dq, J=6.26, 6.00 Hz, 2 H), 3.89 (t, J=13.89 Hz, 1 H), 3.10 - 3.25 (m, 1 H), 2.70 - 2.88 (m, 1 H), 2.63 (t, J=10.76 Hz, 1 H), 1.78 - 1.97 (m, 2 H), 1.45 - 1.60 (m, 1 H), 1.33 - 1.45 (m, 1 H), 1.14 - 1.25 (m, 6 H); Method 1 , retention time: 5.246 min; HRMS: m/z (M+H)⁺ = 382.1521 (Calculated for C₁₈H₂₅C1N₃04 = 382.1528).

LLI06-031)

(R)-ethyl l-(2-(3-(2-chlorophenyl)ureido)propanoyl)piperidine-4-carboxyIate

'H NMR (400 MHz, DMSO-c/6) 5 ppm 8.26 (d, J=4.30 Hz, 1 H), 8.1 1 (dd, J=8.61 , 1.17 Hz, 1 H), 7.45 (d, J=7.83 Hz, 1 H), 7.39 (dd, J=8.02, 1.37 Hz, 1 H), 7.22 (t, J=7.63 Hz, 1 H), 6.95 (t, J=7.63 Hz, 1 H), 4.71 (qd, J=7.11, 6.85 Hz, 1 H), 4.16 - 4.31 (m, 1 H), 4.02 - 4.13 (m, 2 H), 3.89 (t, J=13.89 Hz, 1 H), 3.09 - 3.24 (m, 1 H), 2.70 - 2.86 (m, 1 H), 2.57 - 2.68 (m, 1 H), 1.79 - 1.97 (m, 2 H), 1.46 - 1.59 (m, 1 H), 1.32 - 1.46 (m, 1 H), 1.19 (t, J=6.06 Hz, 6 H); Method 1 , retention time: 5.226 min; HRMS: m/z (M+H)⁺ = 382.1516 (Calculated for Ci₈H₂₅ClN₃0₄ = 382.1528).

NCGC00250262 (LLI06-039)

Ethyl l-(2-(2-chlorobenzamido)-2-methylpropanoyl)piperidine-4-carboxylate

Ή NMR (400 MHz, DMSO-t 6) δ ppm 8.75 (s, 1 H), 7.39 - 7.53 (m, 4 H), 4.24 - 4.33 (m, 2 H), 4.06 (q, J=7.04 Hz, 2 H), 2.84 - 3.06 (m, 2 H), 2.54 - 2.63 (m, 1 H), 1.82 (dd, J=13.30, 3.13 Hz, 2 H), 1.37 - 1.51 (m, 8 H), 1.13 - 1.20 (m, 3 H); Method 1 , retention time: 4.771 min; HRMS: m/z (M+H)⁺ = 381.1571 (Calculated for C₁₉H₂₆C1N₂0₄ = 381.1576).

LI06-040)

Ethyl l-(2-(2-(2-chlorophenyl)acetamido)-2-methylpropanoyl)piperidine-4-carboxylate

Ή NMR (400 MHz, DMSO- 6) δ ppm 8.40 (s, 1 H), 7.37 - 7.44 (m, 1 H), 7.30 - 7.35 (m, 1 H), 7.22 - 7.29 (m, 2 H), 4.16 - 4.26 (m, 2 H), 4.01 - 4.09 (m, 2 H), 3.58 (s, 2 H), 2.76 - 2.98 (m, 3 H), 2.51 - 2.57 (m, 2 H), 1.75 (dd, J=13.1 1 , 3.33 Hz, 2 H), 1.32 - 1.38 (m, 6 H), 1.13 - 1.20 (m, 3 H); Method 1, retention time: 4.989 min; HRMS: m/z (M+H)⁺ = 395.1722 (Calculated for C₂oH₂₈ClN₂0₄ = 395.1732).

[0311] NCGC00253898 (LLI06-069)

N-(l-(2,4-difluorobenzyl)-4,5,6,7-tetrahydro-lH-indazol-4-yl)picolinamide

1H NMR (400 MHz, DMSO- 6) δ ppm 8.61 (dq, J=4.74, 0.90 Hz, 1 H), 8.53 (d, J=8.61 Hz, 1 H), 8.05 - 8.1 1 (m, 1 H), 7.97 - 8.05 (m, 1 H), 7.57 - 7.64 (m, 2 H), 7.32 (td, J=8.71, 6.85 Hz, 1 H), 7.24 (ddd, J=10.37, 9.39, 2.54 Hz, 1 H), 7.02 - 7.10 (m, 1 H), 5.23 (s, 2 H), 5.06 (td, J=7.73, 4.89 Hz, 1 H), 2.53 (dd, J=6.65, 1.96 Hz, 2 H), 1.87 - 1.99 (m, 2 H), 1.66 - 1.83 (m, 2 H); Method 1 , retention time: 5.345 min; HRMS: m/z (M+H)⁺ = 369.1515 (Calculated for C₂₀Hi₉F₂N₄O = 369.1521).

[0312] NCGC00253900 (LLI06-072)

N-(l-(2-chIoro-4-fluorobenzyl)-4,5,6,7-tetrahydro-lH-indazol-4-yI)picolinamide 1H NMR (400 MHz, DMSO-76) δ ppm 8.61 (dq, J=4.70, 0.91 Hz, 1 H), 8.54 (d, 7=8.22 Hz, 1 H), 8.05 - 8.10 (m, 1 H), 8.01 (td, J=7.63, 1.57 Hz, 1 H), 7.64 (s, 1 H), 7.60 (ddd, J=7.43, 4.70, 1.17 Hz, 1 H), 7.46 (dd, J=8.80, 2.54 Hz, 1 H), 7.18 - 7.24 (m, 1 H), 7.12 - 7.17 (m, 1 H), 5.29 (s, 2 H), 5.08 (td, J=7.92, 4.89 Hz, 1 H), 2.53 - 2.58 (m, 2 H), 1.95 (dt, 7=8.51, 5.14 Hz, 2 H), 1.68 - 1.83 (m, 2 H); Method 1 , retention time: 5.632 min; HRMS: m/z (M+H)⁺ = 385.1209 (Calculated for C₂oH₁₉ClFN₄0 = 385.1226).

[0313] NCGC00253901 (LLI06-073)

N-(l-(pyridin-2-yl)-4,5,6,7-tetrahydro-lH-indazol-4-yl)picolinamide

1H NMR (400 MHz, DMSO-t/6) δ ppm 8.75 (d, 7=7.83 Hz, 1 H), 8.63 (dq, J=4.74, 0.90 Hz, 1 H), 8.37 - 8.40 (m, 1 H), 8.36 (s, 1 H), 8.09 - 8.13 (m, 1 H), 8.02 (td, J=7.73, 1.76 Hz, 1 H), 7.91 - 7.97 (m, 1 H), 7.82 - 7.87 (m, 1 H), 7.61 (ddd, 7=7.43, 4.70, 1.17 Hz, 1 H), 7.28 (ddd, J=7.34, 4.99, 0.98 Hz, 1 H), 5.14 (td, 7=7.73, 4.89 Hz, 1 H), 2.67 - 2.73 (m, 2 H), 2.00 - 2.07 (m, 2 H), 1.76 - 1.92 (m, 2 H); Method 1, retention time: 5.153 min; HRMS: m/z (M+H)⁺ = 320.1496 (Calculated for Ci₈Hi₈N₅0 = 320.1506).

[0314] NCGC00253902 (LLI06-074_PK2)

N-(l-(5-fluoropyridin-3-yl)-4,5,6,7-tetrahydro-lH-indazol-4-yl)picolinamide

Ή NMR (400 MHz, DMSO-76) δ ppm 8.95 - 9.00 (m, 1 H), 8.78 (d, J=8.61 Hz, 1 H), 8.61 - 8.66 (m, 1 H), 8.43 - 8.49 (m, 2 H), 8.18 (dt, J=10.56, 2.35 Hz, 1 H), 8.09 - 8.14 (m, 1 H), 8.03 (td, 7=7.73, 1.76 Hz, 1 H), 7.61 (ddd, 7=7.53, 4.79, 1.37 Hz, 1 H), 5.21 (td, 7=7.92, 4.50 Hz, 1 H), 2.66 - 2.73 (m, 2 H), 1.98 - 2.06 (m, 2 H), 1.75 - 1.89 (m, 2 H); Method 1 , retention time: 5.005 min; HRMS: m/z (M+H)⁺ = 338.1400 (Calculated for Ci₈H_{! 7}FN₅0 = 338.1412). [0315] NCGC00253894 (LLI06-078)

N-(l-(4,6-dimethylpyridin-2-yl)-4,5,6,7-tetrahydro-lH-indazol-4-yl)picolinamide

1H NMR (400 MHz, DMSO-<¾) 5 ppm 8.75 (d, 7 = 8.2 Hz, 1H), 8.63 (ddd, 7 = 4.8, 1.5, 0.8 Hz, 1 H), 8.30 (d, J= 0.7 Hz, 1H), 8.11 (dt, 7= 7.9, 1.1 Hz, 1H), 8.03 (td, J= 7.7, 1.7 Hz, 1H), 7.62 (ddd, J - 7.5, 4.8, 1.4 Hz, 1H), 7.52 - 7.50 (m, 1 H), 6.97 (s, 1H), 5.15 (td, 7 = 8.2, 4.6 Hz, 1H), 2.71 - 2.67 (m, 2H), 2.40 (s, 3H), 2.34 (s, 3H), 2.13 - 1.97 (m, 2H), 1.94 - 1.71 (m, 2H).; Method 1, retention time: 5.889 min; HRMS: m/z (M+H)⁺ = 348.1809 (Calculated for C₂oH₂₂N₅0 = 348.1819). 07-027)

2-Bromo-N-(3,4-diethoxyphenethyl)-4H-thieno[3,2-b]pyrrole-5-carboxamide

Ή NMR (400 MHz, DMSO- 6) δ ppm 1 1.78 (br. s., 1 H), 8.28 (t, J=5.67 Hz, 1 H), 7.05 (s, 1 H), 7.01 (d, 7=1.96 Hz, 1 H), 6.84 (d, 7=8.22 Hz, 1 H), 6.81 (d, 7=1.96 Hz, 1 H), 6.71 (dd, 7=8.22, 1.96 Hz, 1 H), 3.96 (qd, 7=6.98, 2.15 Hz, 4 H), 3.40 - 3.48 (m, 2 H), 2.74 (t, 7=7.43 Hz, 2 H), 1.28 (q, 7=7.04 Hz, 6 H); Method 1 , retention time: 6.173 min; HRMS: m/z (M+H)" = 437.0517 (Calculated for CigH₂₂BrN₂0₃S = 437.0529).

LI07-028)

3-Bromo-N-(3,4-diethoxyphenethyl)-4H-thieno[3,2-b]pyrrole-5-carboxamide Ή NMR (400 MHz, DMSO-i/6) 6 ppm 1 1.98 (s, 1 H), 8.26 (t, J=5.48 Hz, 1 H), 7.49 (s, 1 H), 7.09 (d, J=1.57 Hz, 1 H), 6.85 (d, J=8.22 Hz, 1 H), 6.82 (d, J=1.96 Hz, 1 H), 6.72 (dd, J=8.22, 1.96 Hz, 1 H), 3.96 (qd, J=6.98, 3.72 Hz, 4 H), 3.42 - 3.49 (m, 2 H), 2.75 (t, J=7.24 Hz, 2 H), 1.28 (dt, 6 H); Method 1 , retention time: 6.089 min; HRMS: m/z (M+H)⁺ =

437.0515 (Calculated for C₁₉H2₂BrN₂0₃S = 437.0529).

[0318] NCGC00253907 (LLI07-039)

N-(3,4-diethoxyphenethyl)-4H-furo [3,2-b] pyrrole-5-carboxamide

1H NMR (400 MHz, DMSO-^6) δ ppm 1 1.18 (s, 1 H), 8.07 (t, J=5.67 Hz, 1 H), 7.65 (d, J=1.96 Hz, 1 H), 6.84 (d, J=8.22 Hz, 1 H), 6.81 (d, J=1.96 Hz, 1 H), 6.76 (dd, J=1.57, 0.78 Hz, 1 H), 6.71 (dd, J=8.22, 1.96 Hz, 1 H), 6.54 (dd, J=2.35, 0.78 Hz, 1 H), 3.96 (q, J=7.04 Hz, 4 H), 3.38 - 3.46 (m, 2 H), 2.74 (t, J=7.43 Hz, 2 H), 1.28 (q, 6 H); Method 1, retention time: 2.291 min; HRMS: m/z (M+H)⁺ = 343.1646 (Calculated for Ci₉H₂₃N₂0₄ = 343.1652).

[0319] NCGC00263033 (LLI08-031)

(6,7-Diethoxy-3,4-dihydroisoquinolin-2(lH)-yl)(4H-thieno[3,2-b]pyrrol-5-yl)methanone

Ή NMR (400 MHz, DMSO- 6) δ ppm 1 1.70 (s, 1 H), 7.40 (d, J=5.09 Hz, 1 H), 6.96 - 6.99 (m, 1 H), 6.94 (d, J=1.56 Hz, 1 H), 6.84 (s, 1 H), 6.77 (s, 1 H), 4.79 (br. s., 2 H), 3.98 (qd, J=6.98, 4.89 Hz, 4 H), 3.89 (br. s., 2 H), 2.82 (t, J=5.48 Hz, 2 H), 1.30 (td, 6 H); Method 1 , retention time: 2.614 min; HRMS: m/z (M+H)⁺ = 371.1414 (Calculated for C₂₀H₂₃N₂O₃S = 371.1424).

[0320] NCGC00262861 (LLI08-037)

N-(2-(3,4-diethoxyphenyl)propyl)-4H-thieno[3,2-b]pyrrole-5-carboxamide

Ή NMR (400 MHz, DMSO-i/6) 6 ppm 1 1.61 (s, 1 H), 8.14 (t, J=5.87 Hz, 1 H), 7.35 (d, J=5.09 Hz, 1 H), 7.03 (d, J=1.56 Hz, 1 H), 6.94 (dd, J=5.09, 0.78 Hz, 1 H), 6.85 (d, J=8.22 Hz, 1 H), 6.82 (d, J=1.96 Hz, 1 H), 6.73 (dd, J=8.22, 1.96 Hz, 1 H), 3.93 - 4.02 (m, 4 H), 3.32 - 3.39 (m, 2

H), 2.90 - 3.01 (m, 1 H), 1.28 (td, J=7.04, 5.48 Hz, 6 H), 1.20 (d, 3 H); Method 1, retention time: 5.863 min; HRMS: m/z (M+H)⁺ = 373.1570 (Calculated for C₂₀H₂₅N₂O₃S = 373.1580).

[0321] NCGC00263052 (LLI08-045)

N-(3,4-bis(2,2,2-trifluoroethoxy)phenethyl)-4H-thieno[3,2-b]pyrrole-5-carboxamide

Ή NMR (400 MHz, DMSO-i/6) δ ppm 1 1.63 (s, 1 H), 8.25 (t, J=5.67 Hz, 1 H), 7.36 (d, J=5.09 Hz, 1 H), 7.03 - 7.10 (m, 3 H), 6.95 (dd, J=5.09, 0.78 Hz, 1 H), 6.91 (dd, J=8.22, 1.96 Hz, 1 H), 4.68 (qd, J=8.87, 4.70 Hz, 4 H), 3.44 - 3.51 (m, 2 H), 2.80 (t, 2 H); Method 1, retention time: 6.225 min; HRMS: m/z (M+H)⁺ = 467.0840 (Calculated for d₉H₁₇F₆N₂0₃S = 467.0859).

[0322] NCGC00263053 (LLI08-051)

N-(3,4-diethoxyphenethyl)-4-(l-phenylethyl)-4H-thieno[3,2-b]pyrrole-5-carboxamide

Ή NMR (400 MHz, DMSO-i 6) δ ppm 8.37 (t, J=5.67 Hz, 1 H), 7.27 - 7.34 (m, 3 H), 7.20 - 7.27 (m, 3 H), 7.00 (d, J=0.78 Hz, 1 H), 6.88 (q, J=7.30 Hz, 1 H), 6.81 - 6.85 (m, 2 H), 6.70 - 6.74 (m, 2 H), 3.96 (qd, J=7.04, 4.70 Hz, 4 H), 3.40 - 3.47 (m, 2 H), 2.76 (t, J=7.43 Hz, 2 H), 1.84 (d, J=7.04 Hz, 3 H), 1.28 (q, J=7.04 Hz, 6 H); Method 1 , retention time: 6.967 min; HRMS: m/z (M+H)⁺ = 463.2047 (Calculated for C27H31N2O3S = 463.2050). LLI08-052)

N,4-dibenzyl-2-bromo-N-(3,4-diethoxyphenethyl)-4H-thieno[3,2-b]pyrrole-5- carboxamide

Ή NMR (400 MHz, DMSO- 6) δ ppm 7.47 (s, 1 H), 7.40 (s, 1 H), 7.23 - 7.34 (m, 7 H), 7.06 - 7.12 (m, 3 H), 6.77 (d, J=8.22 Hz, 1 H), 6.53 (dd, J=3.91 , 2.35 Hz, 2 H), 5.39 (br. s., 2 H), 4.63 (br. s., 2 H), 3.93 (q, J=6.91 Hz, 4 H), 3.37 - 3.44 (m, 2 H), 2.60 (t, J=7.43 Hz, 2 H), 1.23 - 1.30 (m, 6 H); Method 1, retention time: 7.803 min; HRMS: m/z (M+Na)⁺ = 639.1259 (Calculated for C₃₃H₃₃BrN₂Na0₃S = 639.1287).

[ 08-053)

N,4-dibenzyl-3-bromo-N-(3,4-diethoxyphenethyl)-4H-thieno[3,2-b]pyrrole-5- carboxamide

Ή NMR (400 MHz, DMSO- 6) δ ppm 7.55 (s, 1 H), 7.19 - 7.32 (m, 7 H), 6.94 (br. s., 3 H), 6.77 (d, J=8.22 Hz, 2 H), 6.51 (br. s., 2 H), 5.61 (br. s., 2 H), 4.61 (br. s., 2 H), 3.94 (q, J=7.04 Hz, 4 H), 3.32 - 3.40 (m, 2 H), 2.56 (t, J=7.43 Hz, 2 H), 1.21 - 1.33 (m, 6 H); Method 1 , retention time: 7.751 min; HRMS: m/z (M+H)⁺ = 617.1461 (Calculated for

C₃₃H₃₄BrN₂0₃S = 617.1468).

[0325] NCGC00263047 (LLI08-054)

(4-Benzyl-4H-thieno[3,2-b]pyrrol-5-yl)(6,7-diethoxy-3,4-dihydroisoquinolin-2(lH)- yl)methanone

1H NMR (400 MHz, DMSO- 6) δ ppm 7.40 (d, J=5.48 Hz, 1 H), 7.21 (d, J=4.70 Hz, 1 H), 7.07 (br. s., 5 H), 6.79 (d, J=0.78 Hz, 1 H), 6.70 (s, 2 H), 5.45 (s, 2 H), 4.64 (s, 2 H), 3.89 - 4.02 (m, 4 H), 3.72 (t, J=5.48 Hz, 2 H), 2.65 (t, J=5.48 Hz, 2 H), 1.24 - 1.35 (m, 6 H);

Method 1, retention time: 3.089 min; HRMS: m/z (M+H)⁺ = 461.1884 (Calculated for C₂₇H₂₉N₂0₃S = 461.1893).

LI08-055)

N,4-dibenzyl-N-(2-(3,4-diethoxyphenyl)propyl)-4H-thieno[3,2-b]pyrrole-5-carboxamide

Ή NMR (400 MHz, DMSO- 6) δ ppm 7.36 (d, J=5.48 Hz, 1 H), 7.21 - 7.32 (m, 7 H), 7.09 (dd, J=7.43, 1.96 Hz, 3 H), 7.06 (d, J=5.48 Hz, 2 H), 6.79 (d, J=8.22 Hz, 1 H), 6.56 - 6.63 (m, 1 H), 6.49 - 6.55 (m, 1 H), 5.33 (br. s., 2 H), 4.70 (d, J=16.04 Hz, 2 H), 3.95 (q, J=6.78 Hz, 4 H), 3.47 (dd, J=12.91 , 6.26 Hz, 2 H), 3.05 (dd, J=8.22, 5.48 Hz, 1 H), 1.22 - 1.32 (m, 6 H), 1.00 - 1.08 (m, 3 H); Method 1 , retention time: 7.624 min; HRMS: m/z (M+H)⁺ = 553.2507 (Calculated for C^Hsv^OsS = 553.2519).

I08-057)

4-BenzyI-2-bromo-N-(3,4-diethoxyphenethyl)-4H-thieno[3,2-b]pyrroIe-5-carboxamide 1H NMR (400 MHz, DMSO- 6) δ ppm 8.36 (t, J=5.48 Hz, 1 H), 7.46 (s, 1 H), 7.20 - 7.31 (m, 3 H), 7.1 1 - 7.16 (m, 2 H), 7.01 - 7.04 (m, 1 H), 6.82 (d, J=8.22 Hz, 1 H), 6.78 (d, J=1.96 Hz, 1 H), 6.67 (dd, J=8.22, 1.96 Hz, 1 H), 5.73 - 5.76 (m, 2 H), 3.95 (qd, J=7.04, 3.91 Hz, 4 H), 3.35 - 3.44 (m, 2 H), 2.71 (t, J=7.24 Hz, 2 H), 1.28 (dt, 6 H); Method 1, retention time: 3.237 min; HRMS: m/z (M+H)⁺ = 527.0979 (Calculated for C₂6H₂₈BrN₂0₃S = 527.0999).

LI08-058)

4-Benzyl-3-bromo-N-(3,4-diethoxyphenethyl)-4H-thieno[3,2-b]pyrrole-5-carboxamide

1H NMR (400 MHz, DMSO-i/6) δ ppm 8.42 (t, J=5.67 Hz, 1 H), 7.56 (s, 1 H), 7.15 - 7.30 (m, 3 H), 7.1 1 (s, 1 H), 6.93 (d, J=7.04 Hz, 2 H), 6.80 (d, J=8.22 Hz, 1 H), 6.77 (d, J=l .96 Hz, 1 H), 6.64 (dd, J=8.22, 1.96 Hz, 1 H), 6.03 (s, 2 H), 3.95 (qd, J=6.91, 2.35 Hz, 4 H), 3.33 - 3.40 (m, 2 H), 2.68 (t, J-7.43 Hz, 2 H), 1.28 (q, 6 H); Method 1 , retention time: 7.170 min;

HRMS: m/z (M+H)⁺ = 527.0985 (Calculated for C₂₆H₂₈BrN₂0₃S = 527.0999).

LI08-059)

4-Benzyl-N-(2-(3,4-diethoxyphenyl)propyl)-4H-thieno[3,2-b]pyrrole-5-carboxamide

Ή NMR (400 MHz, DMSO-i 6) δ ppm 8.23 (t, J=5.87 Hz, 1 H), 7.40 (d, J=5.48 Hz, 1 H), 7.17 - 7.28 (m, 3 H), 7.10 - 7.17 (m, 3 H), 7.03 (s, 1 H), 6.83 (d, J=8.22 Hz, 1 H), 6.80 (d, J=1.96 Hz, 1 H), 6.70 (dd, J=8.22, 2.35 Hz, 1 H), 5.75 (s, 2 H), 3.92 - 4.01 (m, 4 H), 3.29 - 3.35 (m, 2 H), 2.91 - 2.98 (m, 1 H), 1.28 (dt, J=8.22, 7.04 Hz, 6 H), 1.16 (d, J=6.65 Hz, 3 H); Method 1 , retention time: 6.949 min; HRMS: m/z (M+H)⁺ = 463.2029 (Calculated for C2₇H₃,N₂0₃S = 463.2050).

[0330] NCGC00263030 (LLI08-060)

N-(3,4-diisopropoxyphenethyl)-4H-thieno[3,2-b]pyrrole-5-carboxamide

1H NMR (400 MHz, DMSO-i 6) δ ppm 11.62 (s, 1 H), 8.24 (t, J=5.48 Hz, 1 H), 7.36 (d, J=5.09 Hz, 1 H), 7.04 (d, J=1.57 Hz, 1 H), 6.95 (d, J=5.09 Hz, 1 H), 6.85 (d, J=7.83 Hz, 1 H), 6.82 (d, J=2.35 Hz, 1 H), 6.74 (dd, J=8.02, 2.15 Hz, 1 H), 4.35 - 4.44 (m, J=12.23, 6.02, 6.02, 3.52 Hz, 2 H), 3.40 - 3.47 (m, 2 H), 2.75 (t, J=7.24 Hz, 2 H), 1.20 (dd, J=10.37, 6.06 Hz, 12 H); Method 1, retention time: 6.243 min; HRMS: m/z (M+H)⁺ = 387.1727 (Calculated for C₂iH₂₇N₂0₃S = 387.1737).

(LLI08-061)

4-Benzyl-N-(3,4-diisopropoxyphenethyl)-4H-thieno[3,2-b]pyrrole-5-carboxamide

Ή NMR (400 MHz, DMSO- 6) δ ppm 8.31 (t, J=5.67 Hz, 1 H), 7.41 (d, J=5.48 Hz, 1 H), 7.17 - 7.30 (m, 3 H), 7.1 1 - 7.17 (m, 3 H), 7.08 (s, 1 H), 6.84 (d, J=8.22 Hz, 1 H), 6.80 (d, J=2.35 Hz, 1 H), 6.70 (dd, J=8.02, 2.15 Hz, 1 H), 5.78 (s, 2 H), 4.35 - 4.45 (m, J=12.13, 6.06, 6.06, 5.87 Hz, 2 H), 3.36 - 3.44 (m, 2 H), 2.72 (t, J-7.24 Hz, 2 H), 1.20 (dd, J=9.98, 6.06 Hz, 12 H); Method 1 , retention time: 7.233 min; HRMS: m/z (M+H)⁺ = 477.2195 (Calculated for C₂₈H₃3N₂0₃S = 477.2206).

[0332] NCGC00263067 (LLI08-076)

4-Benzyl-N-(3,4-bis(2,2,2-trifluoroethoxy)phenethyl)-4H-thieno[3,2-b]pyrroIe-5- carboxamide Ή NMR (400 MHz, DMSO- 6) δ ppm 8.33 (t, J=5.48 Hz, 1 H), 7.42 (d, J=5.48 Hz, 1 H), 7.17 - 7.30 (m, 3 H), 7.1 1 - 7.17 (m, 3 H), 7.04 - 7.09 (m, 3 H), 6.87 (dd, J=8.22, 1.96 Hz, 1 H), 5.78 (s, 2 H), 4.67 (qd, J=8.87, 5.48 Hz, 4 H), 3.39 - 3.47 (m, 2 H), 2.77 (t, 2 H); Method 1 , retention time: 3.162 min; HRMS: m/z (M+H)⁺ = 557.1320 (Calculated for C₂₆H₂₃F₆N₂0₃S = 557.1328).

[0333] NCGC00263278 (LLI08-084)

5-(4-benzyl-4H-thieno[3,2-b]pyrrol-5-yl)-3-(3,4-diethoxybenzyl)-l,2,4-oxadiazole

1H NMR (400 MHz, DMSO-d6) 6 ppm 7.63 (d, J=5.48 Hz, 1 H), 7.46 (s, 1 H), 7.28 (d, j=5.48 Hz, 1 H), 7.17 - 7.23 (m, 3 H), 7.05 - 7.10 (m, 2 H), 6.93 (d, j=1.96 Hz, 1 H), 6.85 - 6.90 (m, 1 H), 6.77 - 6.82 (m, 1 H), 5.86 (s, 2 H), 4.02 (s, 2 H), 3.98 (q, J=7.04 Hz, 2 H), 3.92 (q, J=6.78 Hz, 2 H), 1.28 (dt, J=l 1.84, 6.99 Hz, 6 H) Method 1, retention time: 3.421 min; HRMS: m/z (M+H)⁺ = 460.1674 (Calculated for C₂₆H₂6N₃0₃S = 460.1689).

[0334] NCGC00263797 (LLI09-014)

(R)-N-(l-(4-(2-(2-(2-aminoethoxy)ethoxy)ethoxy)phenyl)-4,5,6,7-tetrahydro-lH-indazol- 4-yl)picolinamide

Ή NMR (400 MHz, DMSO-i/6) δ ppm 8.62 (dq, J=4.70, 0.91 Hz, 1 H), 8.55 (d, J=8.61 Hz, 1 H), 8.07 - 8.13 (m, 1 H), 8.02 (td, J=7.73, 1.76 Hz, 1 H), 7.75 (br. s., 2 H), 7.61 (ddd, J=7.53, 4.79, 1.37 Hz, 1 H), 7.51 (s, 1 H), 7.40 - 7.49 (m, 2 H), 7.02 - 7.10 (m, 2 H), 5.10 - 5.20 (m, 1 H), 4.1 1 - 4.20 (m, 2 H), 3.74 - 3.83 (m, 2 H), 3.57 - 3.69 (m, 5 H), 2.93 - 3.03 (m, 2 H), 2.61 - 2.79 (m, 2 H), 1.72 - 2.03 (m, 5 H); Method 1 , retention time: 1.879 min; HRMS: m/z (M+H)⁺ = 466.2436 (Calculated for C₂₅H₃₂N₅0₄ = 466.2449).

63804 (LLI09-026)

N-(l-(4-methoxyphenyl)-lH-indol-4-yl)-2-phenylacetamide

Ή NMR (400 MHz, DMSO-c/6) δ ppm 9.89 (s, 1 H), 7.65 (d, J=7.43 Hz, 1 H), 7.52 (d, J=3.52 Hz, 1 H), 7.44 - 7.49 (m, 2 H), 7.38 - 7.42 (m, 2 H), 7.35 (t, J=7.63 Hz, 2 H), 7.23 - 7.28 (m, 1 H), 7.06 - 7.19 (m, 4 H), 6.91 (d, J=3.13 Hz, 1 H), 3.83 (s, 3 H), 3.80 (s, 2 H); Method 1, retention time: 3.059 min; HRMS: m/z (M+H)⁺ = 357.1590 (Calculated for C₂₃¾iN₂0₂ = 357.1598).

[0336] NCGC00263805 (LLI09-027)

tert-Butyl 2-(l-(4-methoxyphenyl)-lH-indol-4-ylcarbamoyl)piperidine-l-carboxylate

Ή NMR (400 MHz, DMSO-i 6) δ ppm 9.70 (br. s., 1 H), 7.52 (d, J=3.13 Hz, 2 H), 7.44 - 7.50 (m, 2 H), 7.16 - 7.21 (m, 1 H), 7.08 - 7.16 (m, 3 H), 6.83 (d, J=2.74 Hz, 1 H), 4.78 - 4.95 (m, 2 H), 3.79 - 3.87 (m, 4 H), 2.09 - 2.21 (m, 2 H), 1.58 - 1.83 (m, 4 H), 1.39 (br. s., 9 H); Method 1 , retention time: 3.369 min; HRMS: m/z (M+H)⁺ = 450.2377 (Calculated for C26H32N3O4 = 450.2387).

[0337] NCGC00263792 (LLI09-029)

N-(l-(4-methoxyphenyl)-4,5,6,7-tetrahydro-lH-indazol-4-yl)-6-methylpicolinamide

Ή NMR (400 MHz, DMSO-J6) δ ppm 8.46 (d, J=8.61 Hz, 1 H), 7.87 - 7.92 (m, 2 H), 7.51 (s, 1 H), 7.42 - 7.49 (m, 3 H), 7.03 - 7.08 (m, 2 H), 5.12 - 5.19 (m, 1 H), 3.81 (s, 3 H), 2.64 - 2.78 (m, 2 H), 2.52 (d, J=5.09 Hz, 3 H), 1.90 - 2.02 (m, 2 H), 1.75 - 1.88 (m, 2 H); Method 1 , retention time: 2.620 min; HRMS: m/z (M+H)⁺ = 363.1815 (Calculated for C₂iH₂₃N₄0₂ = 363.1816).

[0338] NCGC00263793 L(LLI09-030)

5-Chloro-N-(l-(4-methoxyphenyl)-4,5,6,7-tetrahydro-lH-indazol-4-yl)picoIinamide

1H NMR (400 MHz, DMSO-^6) d ppm 8.67 (d, J=1.96 Hz, 1 H), 8.60 (d, J=8.22 Hz, 1 H), 8.13 - 8.17 (m, 1 H), 8.08 - 8.1 1 (m, 1 H), 7.49 (s, 1 H), 7.43 - 7.48 (m, 2 H), 7.03 - 7.08 (m, 2 H), 5.1 1 - 5.17 (m, 1 H), 3.81 (s, 3 H), 2.69 (dt, J=l 0.96, 5.48 Hz, 2 H), 1.91 - 1.99 (m, 2 H), 1.73 - 1.88 (m, 2 H); Method 1, retention time: 2.819 min; HRMS: m/z (M+H)⁺ = 383.1266 (Calculated for C₂₀H₂₀ClN₄O₂ = 383.1269).

9-036)

l-(4-Chloro-3-fluorobenzyl)-N-(3,4-diethoxyphenethyI)-lH-pyrrole-2-carboxamide Ή NMR (400 MHz, DMSO-i 6) δ ppm 8.07 (t, J=5.67 Hz, 1 H), 7.50 (t, J=8.02 Hz, 1 H), 7.04 - 7.10 (m, 2 H), 6.91 (dd, J=8.41 , 1.37 Hz, 1 H), 6.77 - 6.83 (m, 2 H), 6.75 (d, J=1.96 Hz, 1 H), 6.63 (dd, J=8.22, 1.96 Hz, 1 H), 6.09 (dd, J=3.91 , 2.74 Hz, 1 H), 5.57 (s, 2 H), 3.94 (quin, J=7.04 Hz, 4 H), 3.28 - 3.37 (m, 2 H), 2.67 (t, J=7.24 Hz, 2 H), 1.28 (q, J=7.04 Hz, 6 H); Method 1, retention time: 3.230 min; HRMS: m/z (M+H)⁺ = 445.1670 (Calculated for C₂₄H₂₇C1FN₂0₃ = 445.1689).

[0340] NCGC00263803 (LLI09-038)

N-(l-(4-methoxyphenyl)-4,5,6,7-tetrahydro-lH-indazol-4-yl)benzamide

1H NMR (400 MHz, DMSO-i/6) δ ppm 8.63 (d, J=7.83 Hz, 1 H), 7.88 - 7.93 (m, 2 H), 7.51 (s, 2 H), 7.41 - 7.48 (m, 4 H), 7.02 - 7.08 (m, 2 H), 5.13 - 5.21 (m, 1 H), 3.81 (s, 3 H), 2.67 - 2.74 (m, 2 H), 1.93 - 2.01 (m, 2 H), 1.73 - 1.80 (m, 2 H); Method 1, retention time: 2.673 min; HRMS: m/z (M+H)⁺ = 348.1699 (Calculated for C₂iH₂₂N₃0₂ = 348.1707).

LI09-049)

4-Benzyl-N-(3,4-diethoxyphenethyl)-N-methyl-4H-thieno[3,2-b]pyrrole-5-carboxamide

Ή NMR (400 MHz, DMSO-t/6) δ ppm 7.35 (d, J=5.48 Hz, 1 H), 7.19 - 7.30 (m, 3 H), 7.07 - 7.14 (m, 3 H), 6.80 (d, J=8.22 Hz, 1 H), 6.60 (br. s., 3 H), 5.32 (br. s., 2 H), 3.84 - 3.98 (m, 4 H), 3.56 (t, J=7.43 Hz, 2 H), 2.96 (s, 3 H), 2.62 - 2.70 (m, 2 H), 1.21 - 1.33 (m, 6 H); Method 1 , retention time: 3.338 min; HRMS: m/z (M+H)⁺ = 463.2039 (Calculated for C₂₇H₃iN₂0₃S = 463.2050).

[0342] NCGC00273464 (LLI09-050)

N-(l-(4-methoxyphenyl)-4,5,6,7-tetrahydro-lH-indazol-4-yI)-3-methylpicolinamide

Ή NMR (400 MHz, DMSO- 6) δ ppm 8.59 (d, J=8.61 Hz, 1 H), 8.41 (dd, J=4.70, 1.57 Hz, 1 H), 7.75 (dd, J=7.83, 0.78 Hz, 1 H), 7.52 (s, 1 H), 7.41 - 7.48 (m, 3 H), 7.02 - 7.09 (m, 2 H), 5.07 - 5.15 (m, 1 H), 3.81 (s, 3 H), 2.69 (q, J=6.00 Hz, 2 H), 2.56 (s, 3 H), 1.87 - 2.01 (m, 2 H), 1.73 -

1.85 (m, 2 H); Method 1, retention time: 2.693 min; HRMS: m/z (M+H)⁺ = 363.1801 (Calculated for C_{2 !}H23N₄0₂ = 363.1816).

[0343] NCGC00273418 (LLI09-051)

N-(l-(4-methoxyphenyl)-4,5,6,7-tetrahydro-lH-indazol-4-yl)-5-methylpicolinamide

1H NMR (400 MHz, DMSO- 6) δ ppm 8.49 (d, J=8.22 Hz, 1 H), 8.45 (d, J=1.96 Hz, 1 H), 7.99 (d, J=7.83 Hz, 1 H), 7.83 (dd, J=7.83, 1.96 Hz, 1 H), 7.49 (s, 1 H), 7.41 - 7.48 (m, 2 H), 7.02 - 7.09 (m, 2 H), 5.09 - 5.18 (m, 1 H), 3.81 (s, 3 H), 2.65 - 2.75 (m, 2 H), 2.38 (s, 3 H), 1.72 - 2.01 (m, 4 H); Method 1 , retention time: 2.820 min; HRMS: m/z (M+H)⁺ = 363.1823 (Calculated for C21 H23N4O2 = 363.1816).

[0344] NCGC00273408 (LLI09-052)

6-Fluoro-N-(l-(4-methoxyphenyl)-4,5,6,7-tetrahydro-lH-indazol-4-yl)picolinamide

Ή NMR (400 MHz, DMSO- 6) 6 ppm 8.54 (d, J=8.22 Hz, 1 H), 8.20 (q, J=8.22 Hz, 1 H), 8.02 (dd, J=7.04, 1.96 Hz, 1 H), 7.50 (s, 1 H), 7.39 - 7.48 (m, 3 H), 7.02 - 7.09 (m, 2 H), 5.11 - 5.19 (m, 1 H), 3.81 (s, 3 H), 2.65 - 2.74 (m, 2 H), 1.95 (dd, J=1 1.35, 4.70 Hz, 2 H), 1.81 - 1.90 (m, 1 H), 1.72 - 1.81 (m, 1 H); Method 1 , retention time: 2.818 min; HRMS: m/z (M+H)⁺ = 367.1548 (Calculated for C₂₀H₂₀FN₄O₂ = 367.1565).

[0345] NCGC00273407 (LLI09-053)

3,5-Difluoro-N-(l-(4-methoxyphenyl)-4,5,6,7-tetrahydro-lH-indazol-4-yI)picoIinamide

1H NMR (400 MHz, DMSO-i/6) δ ppm 8.69 (d, J=7.83 Hz, 1 H), 8.54 (d, J=1.96 Hz, 1 H), 8.08 (ddd, J=10.86, 9.10, 2.35 Hz, 1 H), 7.51 (s, 1 H), 7.41 - 7.48 (m, 2 H), 7.02 - 7.08 (m, 2 H), 5.08 - 5.15 (m, 1 H), 3.80 (s, 3 H), 2.65 - 2.73 (m, 2 H), 1.89 - 2.00 (m, 2 H), 1.74 - 1.84 (m, 2 H); Method 1 , retention time: 2.727 min; HRMS: m/z (M+H)⁺ = 385.1467 (Calculated for C20H19F2N4O2 = 385.1471).

[0346] NCGC00273420 (LLI09-054)

N-(l-(4-methoxyphenyl)-4,5,6,7-tetrahydro-lH-indazol-4-yl)-5- (trifluoromethyl)picolinamide

Ή NMR (400 MHz, DMSO- 6) δ ppm 9.02 (d, J=1.96 Hz, 1 H), 8.80 (d, J=8.22 Hz, 1 H), 8.45 (dd, J=8.22, 2.35 Hz, 1 H), 8.28 (d, J=8.22 Hz, 1 H), 7.51 (s, 1 H), 7.43 - 7.48 (m, 2 H), 7.03 - 7.08 (m, 2 H), 5.18 (dd, J=12.72, 6.85 Hz, 1 H), 3.81 (s, 3 H), 2.69 (ddd, J=16.63, 10.76, 6.65 Hz, 2 H), 1.92 - 2.01 (m, 2 H), 1.88 (dd, J=16.04, 9.39 Hz, 1 H), 1.81 (br. s., 1 H); Method 1 , retention time: 3.062 min; HRMS: m/z (M+H)⁺ = 417.1523 (Calculated for C₂iH₂₀F₃N₄O₂ = 417.1533).

[0347] NCGC00273419 (LLI09-055)

N-(l-(4-methoxyphenyl)-4,5,6,7-tetrahydro-lH-indazol-4-yl)-4-methylpicolinamide

^]H NMR (400 MHz, DMSO-c/6) δ ppm 8.54 (d, J=8.22 Hz, 1 H), 8.46 (d, J=4.70 Hz, 1 H), 7.95 (s, 1 H), 7.49 (s, 1 H), 7.41 - 7.48 (m, 3 H), 7.01 - 7.09 (m, 2 H), 5.10 - 5.18 (m, 1 H), 3.77 - 3.83 (m, 3 H), 2.64 - 2.76 (m, 2 H), 2.43 (s, 3 H), 1.73 - 2.00 (m, 4 H); Method 1 , retention time: 2.777 min; HRMS: m/z (M+H)⁺ = 363.1809 (Calculated for C₂iH₂₃N₄0₂ = 363.1816).

[0348] NCGC00273465 (LLI09-056)

6-Chloro-N-(l-(4-methoxyphenyl)-4,5,6,7-tetrahydro-lH-indazol-4-yl)picolinamide

Ή NMR (400 MHz, DMSO-ώ) δ ppm 8.56 (d, J=8.61 Hz, 1 H), 8.05 - 8.1 1 (m, 2 H), 7.70 - 7.77 (m, 1 H), 7.51 (s, 1 H), 7.43 - 7.49 (m, 2 H), 7.03 - 7.09 (m, 2 H), 5.12 - 5.20 (m, 1 H), 3.81 (s, 3 H), 2.64 - 2.74 (m, 2 H), 1.91 - 2.01 (m, 2 H), 1.82 - 1.91 (m, 1 H), 1.76 (ddd, 1 H); Method 1 , retention time: 2.950 min; HRMS: m/z (M+H)⁺ = 383.1253 (Calculated for C₂oH2oClN₄0₂ = 383.1269).

[0349] NCGC00273466 (LLI09-057)

3-Fluoro-N-(l-(4-methoxyphenyI)-4,5,6,7-tetrahydro-lH-indazol-4-yI)picolinamide

Ή NMR (400 MHz, DMSO-i/6) δ ppm 8.70 (d, J=8.22 Hz, 1 H), 8.45 (ddd, J=4.50, 1.37, 1.17 Hz, 1 H), 7.86 (ddd, J=l 0.96, 8.61 , 1.17 Hz, 1 H), 7.64 (dt, J=8.31 , 4.26 Hz, 1 H), 7.52 (s, 1 H), 7.41 - 7.48 (m, 2 H), 7.02 - 7.09 (m, 2 H), 5.08 - 5.15 (m, 1 H), 3.81 (s, 3 H), 2.65 - 2.73 (m, 2 H), 1.89 - 1.99 (m, 2 H), 1.74 - 1.86 (m, 2 H); Method 1 , retention time: 2.631 min; HRMS: m/z (M+H)⁺ = 367.1550 (Calculated for C₂oH₂oFN₄0₂ = 367.1565).

[0350] NCGC00273410 (LLI09-058)

3,6-DichIoro-N-(l-(4-methoxyphenyl)-4,5,6,7-tetrahydro-lH-indazol-4-yl)picolinamide

Ή NMR (400 MHz, DMSO- 6) δ ppm 8.96 (d, J=7.83 Hz, 1 H), 8.10 (d, J=8.22 Hz, 1 H), 7.65 (d, J=8.61 Hz, 1 H), 7.56 (s, 1 H), 7.42 - 7.48 (m, 2 H), 7.02 - 7.08 (m, 2 H), 5.06 - 5.13 (m, 1 H), 3.80 (s, 3 H), 2.69 (t, J=5.28 Hz, 2 H), 1.89 - 2.00 (m, 2 H), 1.74 - 1.82 (m, 2 H); Method 1, retention time: 2.875 min; HRMS: m/z (M+H)⁺ = 417.0863 (Calculated for C₂₀H₁₉Cl₂N₄O₂ = 417.0880).

67 (LLI09-059)

4-Acetamido-N-(l-(4-methoxyphenyl)-4,5,6,7-tetrahydro-lH-indazol-4-yl)picolinamide

Ή NMR (400 MHz, DMSO- 6) δ ppm 10.59 (s, 1 H), 8.56 (d, J=8.22 Hz, 1 H), 8.45 (d, J=5.48 Hz, 1 H), 8.27 (d, J=1.96 Hz, 1 H), 7.80 (dd, J=5.67, 2.15 Hz, 1 H), 7.50 (s, 1 H), 7.41 - 7.49 (m, 2 H), 7.02 - 7.09 (m, 2 H), 5.08 - 5.18 (m, 1 H), 3.81 (s, 3 H), 2.70 (ddd, 7=1 1.93, 6.26, 6.06 Hz, 2 H), 2.12 (s, 3 H), 1.74 - 2.01 (m, 4 H); Method 1 , retention time: 2.470 min; HRMS: m/z (M+Na)⁺ = 428.1678 (Calculated for C₂₂H₂₃N₅Na0₃ = 428.1693).

[0352] NCGC00273409 (LLI09-060)

4-Chloro-N-(l-(4-methoxyphenyl)-4,5,6,7-tetrahydro-lH-indazol-4-yl)picolinamide

Ή NMR (400 MHz, DMSO-^6) δ ppm 8.68 (d, J=8.61 Hz, 1 H), 8.61 (d, J=4.70 Hz, 1 H), 8.09 (d, J=1.56 Hz, 1 H), 7.78 (dd, J=5.28, 2.15 Hz, 1 H), 7.50 (s, 1 H), 7.42 - 7.49 (m, 2 H), 7.02 - 7.08 (m, 2 H), 5.1 1 - 5.19 (m, 1 H), 3.81 (s, 3 H), 2.65 - 2.74 (m, 2 H), 1.73 - 2.00 (m, 4 H); Method 1 , retention time: 2.973 min; HRMS: m/z (M+H)⁺ = 383.1261 (Calculated for C₂oH₂₀ClN₄0₂ = 383.1269).

[0353] NCGC00273431 (LLI09-061)

5-Fluoro-N-(l-(4-methoxyphenyl)-4,5,6,7-tetrahydro-lH-indazol-4-yl)picolinamide

Ή NMR (400 MHz, DMSO-i/6) δ ppm 8.62 (d, J=2.74 Hz, 1 H), 8.56 (d, J=8.22 Hz, 1 H), 8.17 (dd, J=9.00, 4.70 Hz, 1 H), 7.93 (td, J=8.71 , 2.93 Hz, 1 H), 7.49 (s, 1 H), 7.42 - 7.48 (m, 2 H), 7.02 - 7.08 (m, 2 H), 5.10 - 5.18 (m, 1 H), 3.81 (s, 3 H), 2.70 (ddd, J=1 1.54, 5.67, 5.48 Hz, 2 H), 1.73 - 1.99 (m, 4 H); Method 1 , retention time: 2.839 min; HRMS: m/z (M+H)⁺ = 367.1564 (Calculated for C₂oH₂oFN₄02 = 367.1565).

[0354] NCGC00273468 (LLI09-062)

N-(l-(4-methoxyphenyI)-4,5,6,7-tetrahydro-lH-indazol-4-yI)-3- (trifluoromethyl)picolinamide

Ή NMR (400 MHz, DMSO- 6) 6 ppm 8.88 (d, J=7.83 Hz, 1 H), 8.84 (dd, J=4.70, 0.78 Hz, 1 H), 8.28 (dd, J=8.22, 1.17 Hz, 1 H), 7.71 (dd, J=8.02, 4.89 Hz, 1 H), 7.49 (s, 1 H), 7.40 - 7.48 (m, 2 H), 7.01 - 7.09 (m, 2 H), 5.08 - 5.15 (m, 1 H), 3.80 (s, 3 H), 2.68 (t, J=5.09 Hz, 2 H), 1 .94

(ddd, J=10.76, 5.28, 5.09 Hz, 2 H), 1.72 - 1.82 (m, 2 H); Method 1 , retention time: 2.742 min; HRMS: m/z (M+Na)⁺ = 439.1331 (Calculated for C₂iHi₉F₃N₄Na0₂ = 439.1352).

0273469 (LLI09-063)

6-acetamido-3-chloro-N-(l-(4-methoxyphenyl)-4,5,6,7-tetrahydro-lH-indazol-4- yl)picolinamide

Ή NMR (400 MHz, DMSO-i/6) δ ppm 10.83 (s, 1 H), 8.83 (d, J=8.22 Hz, 1 H), 8.13 (d, J=9.00 Hz, 1 H), 7.94 (d, J=8.61 Hz, 1 H), 7.55 (s, 1 H), 7.39 - 7.49 (m, 2 H), 7.00 - 7.09 (m, 2 H), 5.04 - 5.14 (m, 1 H), 3.80 (s, 3 H), 2.69 (t, J=5.48 Hz, 2 H), 2.09 (s, 3 H), 1.87 - 1.99 (m, 2 H), 1.70 -

1.82 (m, 2 H); Method 1 , retention time: 2.653 min; HRMS: m/z (M+H)⁺ = 440.1475

(Calculated for C₂₂H₂₃C1N₅0₃ - 440.1484).

[0356] NCGC00273402 (LLI09-065)

4-Chloro-N-(l-(4-methoxyphenyl)-4,5,6,7-tetrahydro-lH-indazol-4-yl)-3- (trifluoromethyl)benzamide

Ή NMR (400 MHz, DMSO- 6) δ ppm 9.03 (d, J=7.43 Hz, 1 H), 8.36 (d, J=1.96 Hz, 1 H), 8.21 (dd, J=8.41 , 2.15 Hz, 1 H), 7.85 (d, J=8.61 Hz, 1 H), 7.55 (s, 1 H), 7.42 - 7.48 (m, 2 H), 7.02 - 7.09 (m, 2 H), 5.16 (t, J=6.65 Hz, 1 H), 3.81 (s, 3 H), 2.68 - 2.76 (m, 2 H), 1.92 - 2.01 (m, 2 H), 1.77 (dd, 2 H); Method 1 , retention time: 3.21 1 min; HRMS: m/z (M+H)⁺ = 450.1 184 (Calculated for C₂₂H₂oClF3N₃0₂ = 450.1191).

[0357] NCGC00273443 (LLI09-066)

2-Chloro-N-(l-(4-methoxyphenyl)-4,5,6,7-tetrahydro-lH-indazol-4-yl)benzamide

Ή NMR (400 MHz, DMSO-i/6) δ ppm 8.72 (d, J=8.22 Hz, 1 H), 7.57 (s, 1 H), 7.34 - 7.51 (m, 6 H), 7.01 - 7.07 (m, 2 H), 5.06 - 5.13 (m, 1 H), 3.80 (s, 3 H), 2.68 (t, J=5.09 Hz, 2 H), 1.96 (dd, J=l 1.15, 4.89 Hz, 2 H), 1.71 - 1.79 (m, 2 H); Method p retention time: 2.853 min; HRMS: m/z (M+H)⁺ = 382.1319 (Calculated for C₂iH₂iClN₃0₂ = 382.1317).

[0358] NCGC00273444 (LLI09-067)

3,4-Difluoro-N-(l-(4-methoxyphenyl)-4,5,6,7-tetrahydro-lH-indazol-4-yl)benzamide

1H NMR (400 MHz, DMSO- 6) δ ppm 8.76 (d, J=7.83 Hz, 1 H), 7.97 (ddd, J=l 1.74, 7.83, 2.35 Hz, 1 H), 7.78 - 7.85 (m, J=8.56, 2.89, 1.52, 1.52 Hz, 1 H), 7.49 - 7.59 (m, 2 H), 7.41 - 7.49 (m, 2 H), 7.01 - 7.09 (m, 2 H), 5.09 - 5.18 (m, 1 H), 3.81 (s, 3 H), 2.67 - 2.74 (m, 2 H), 1.91 - 2.01 (m, 2 H), 1.70 - 1.82 (m, 2 H); Method 1, retention time: 2.942 min; HRMS: m/z (M+H)⁺ = 384.1500 (Calculated for C2iH₂oF₂N₃0₂ = 384.1518).

00273447 (LLI09-068)

N-(l-(4-methoxyphenyl)-4,5,6,7-tetrahydro-lH-indazol-4-yl)-2-methylbenzamide

1H NMR (400 MHz, DMSO- 6) δ ppm 8.50 (d, J=8.22 Hz, 1 H), 7.56 (s, 1 H), 7.41 - 7.48 (m, 2 H), 7.27 - 7.35 (m, 2 H), 7.17 - 7.25 (m, 2 H), 7.01 - 7.07 (m, 2 H), 5.08 - 5.15 (m, 1 H), 3.80 (s, 3 H), 2.64 - 2.71 (m, 2 H), 2.37 (s, 3 H), 1.92 - 2.00 (m, 2 H), 1.70 - 1.78 (m, 2 H); Method 1 , retention time: 2.855 min; HRMS: m/z (M+H)⁺ = 362.1864 (Calculated for C₂₂H₂4N₃0₂ = 362.1863).

[0360] NCGC00273448 (LLI09-069)

N-(l-(4-methoxyphenyl)-4,5,6,7-tetrahydro-lH-indazol-4-yl)-4- (trifluoromethoxy)benzamide

Ή NMR (400 MHz, DMSO-^6) δ ppm 8.77 (d, J=7.83 Hz, 1 H), 8.00 - 8.06 (m, 2 H), 7.53 (s, 1 H), 7.45 (d, J=9.00 Hz, 4 H), 7.02 - 7.09 (m, 2 H), 5.12 - 5.20 (m, 1 H), 3.81 (s, 3 H), 2.68 - 2.74 (m, 2 H), 1.92 - 2.01 (m, 2 H), 1.72 - 1.81 (m, 2 H); Method 1 , retention time: 6.1 19 min; HRMS: m/z (M+H)⁺ = 432.1517 (Calculated for C22H21F3N3O3 = 432.1530).

00273449 (LLI09-070)

N-(l-(4-methoxyphenyl)-4,5,6,7-tetrahydro-lH-indazol-4-yl)-2- (trifluoromethyl)benzamide

Ή NMR (400 MHz, DMSO-t 6) δ ppm 8.78 (d, J=8.22 Hz, 1 H), 7.77 (d, J=7.83 Hz, 1 H), 7.71 (t, J=7.43 Hz, 1 H), 7.63 (t, J=7.63 Hz, 1 H), 7.51 - 7.57 (m, 2 H), 7.41 - 7.47 (m, 2 H), 7.00 - 7.08 (m, 2 H), 5.06 - 5.13 (m, 1 H), 3.80 (s, 3 H), 2.67 (t, J=5.28 Hz, 2 H), 1.94 (td, J=10.17, 4.70 Hz, 2 H), 1 .74 (td, 2 H); Method 1 , retention time: 2.914 min; HRMS: m/z (M+H)⁺ = 416.1573 (Calculated for C₂₂H₂iF₃N₃0₂ = 416.1580).

[0362] NCGC00274450 (LLI09-071 )

N-(l-(4-methoxyphenyl)-4,5,6,7-tetrahydro-lH-indazol-4-yl)-2,4-dimethylbenzamide

Ή NMR (400 MHz, DMSO-i/6) 5 ppm 8.40 (d, J=8.22 Hz, 1 H), 7.54 (s, 1 H), 7.40 - 7.48 (m, 2 H), 7.24 (d, J=7.83 Hz, 1 H), 6.98 - 7.08 (m, 4 H), 5.06 - 5.13 (m, 1 H), 3.80 (s, 3 H), 2.64 - 2.70 (m, 2 H), 2.34 (s, 3 H), 2.28 (s, 3 H), 1.92 - 2.00 (m, 2 H), 1.69 - 1.78 (m, 2 H); Method 1, retention time: 2.975 min; HRMS: m/z (M+H)⁺ = 376.2009 (Calculated for C₂₃H₂₆N₃0₂ = 376.2020).

[0363] NCGC00273451 (LLI09-072)

3-fluoro-N-(l-(4-methoxyphenyl)-4,5,6,7-tetrahydro-lH-indazol-4-yl)-4- (trifluoromethyl)benzamide

1H NMR (400 MHz, DMSO- 6) δ ppm 8.97 (d, J=7.83 Hz, 1 H), 7.98 (d, J=l 1.74 Hz, 1 H), 7.87 - 7.96 (m, 2 H), 7.55 (s, 1 H), 7.41 - 7.49 (m, 2 H), 7.01 - 7.09 (m, 2 H), 5.12 - 5.21 (m, 1 H), 3.81 (s, 3 H), 2.68 - 2.75 (m, 2 H), 1.92 - 2.02 (m, 2 H), 1.72 - 1.84 (m, 2 H); Method 1 , retention time: 3.131 min; HRMS: m/z (M+H)⁺ = 434.1483 (Calculated for C₂₂H₂oF₄N₃02 = 434.1486).

[0364] NCGC00273452 (LLI09-073)

N-(l-(4-methoxyphenyl)-4,5,6,7-tetrahydro-lH-indazol-4-yl)-4- (trifluoromethyl)benzamide

Ή NMR (400 MHz, DMSO-i 6) δ ppm 8.90 (d, J=7.83 Hz, 1 H), 8.10 (d, J=8.22 Hz, 2 H), 7.84 (d, J=8.22 Hz, 2 H), 7.54 (s, 1 H), 7.42 - 7.49 (m, 2 H), 7.01 - 7.09 (m, 2 H), 5.14 - 5.21 (m, 1 H), 3.81 (s, 3 H), 2.71 (br. s., 2 H), 1.93 - 2.01 (m, 2 H), 1.72 - 1.81 (m, 2 H); Method 1, retention time: 3.065 min; HRMS: m/z (M+H)⁺ = 416.1570 (Calculated for C₂₂H₂iF₃N₃0₂ = 416.1580).

[0365] NCGC00273434 (LLI09-074)

N-(l-(4-methoxyphenyl)-4,5,6,7-tetrahydro-lH-indazol-4-yl)-3- (trifluoromethoxy)benzamide

1H NMR (400 MHz, DMSO-i 6) δ ppm 8.85 (d, J=7.83 Hz, 1 H), 7.97 (dt, J=7.73, 1.22 Hz, 1 H), 7.88 (s, 1 H), 7.61 (t, J=7.83 Hz, 1 H), 7.51 - 7.57 (m, 2 H), 7.42 - 7.48 (m, 2 H), 7.01 - 7.09 (m, 2 H), 5.13 - 5.20 (m, 1 H), 3.81 (s, 3 H), 2.71 (br. s., 2 H), 1.92 - 2.01 (m, 2 H), 1.72 - 1.81 (m, 2 H); Method 1 , retention time: 6.144 min; HRMS: m/z (M+H)⁺ = 432.1512 (Calculated for C₂₂H₂iF₃N₃0₃ = 432.1530).

[0366] NCGC00273435 (LLI09-075)

2-Fluoro-N-(l-(4-methoxyphenyl)-4,5,6,7-tetrahydro-lH-indazoI-4-yl)-3- (trifluoromethyl)benzamide

Ή NMR (400 MHz, DMSO- 6) δ ppm 8.88 (d, J=7.83 Hz, 1 H), 7.84 - 7.93 (m, 2 H), 7.57 (s, 1 H), 7.41 - 7.50 (m, 3 H), 7.01 - 7.08 (m, 2 H), 5.08 - 5.16 (m, 1 H), 3.80 (s, 3 H), 2.69 (t, J=5.48 Hz, 2 H), 1.88 - 2.01 (m, 2 H), 1.72 - 1.83 (m, 2 H); Method 1 , retention time: 6.061 min; HRMS: m/z (M+H)⁺ = 434.1479 (Calculated for C₂₂H₂₀F₄N₃O₂ = 434.1486).

[0367] NCGC00273436 (LLI09-076)

N-(l-(4-methoxyphenyl)-4,5,6,7-tetrahydro-lH-indazol-4-yl)-3- (trifluoromethyl)benzamide

Ή NMR (400 MHz, DMSO- 6) δ ppm 8.95 (d, J=7.83 Hz, 1 H), 8.27 (s, 1 H), 8.22 (d, J=7.83 Hz, 1 H), 7.90 (d, J=7.83 Hz, 1 H), 7.71 (t, J=7.83 Hz, 1 H), 7.55 (s, 1 H), 7.42 - 7.49 (m, 2 H), 7.02 - 7.09 (m, 2 H), 5.15 - 5.23 (m, 1 H), 3.81 (s, 3 H), 2.72 (br. s., 2 H), 1.92 - 2.02 (m, 2 H), 1.72 - 1.82 (m, 2 H); Method 1 , retention time: 6.036 min; HRMS: m/z (M+Na)⁺ = 438.1383 (Calculated for C₂₂H₂oF₃N₃Na0₂ = 438.1400).

[0368] NCGC00273437 (LLI09-077)

3-Chloro-N-(l-(4-methoxyphenyl)-4,5,6,7-tetrahydro-lH-indazol-4-yl)-4- methylbenzamide

1H NMR (400 MHz, DMSO-i/6) δ ppm 8.71 (d, J=7.83 Hz, 1 H), 7.97 (d, J=1.57 Hz, 1 H), 7.79 (dd, J=7.83, 1.57 Hz, 1 H), 7.52 (s, 1 H), 7.41 - 7.48 (m, 3 H), 7.02 - 7.08 (m, 2 H), 5.1 1 - 5.18 (m, 1 H), 3.81 (s, 3 H), 2.67 - 2.74 (m, 2 H), 2.37 (s, 3 H), 1.95 (td, J=5.67, 3.52 Hz, 2 H), 1.71 -

1.81 (m, 2 H); Method 1, retention time: 3.121 min; HRMS: m/z (M+H)⁺ = 396.1454 (Calculated for C₂₂H₂₃C1N₃0₂ = 396.1473).

[0369] NCGC00273438 (LLI09-078)

4-Fluoro-N-(l-(4-methoxyphenyl)-4,5,6,7-tetrahydro-lH-indazol-4-yl)benzamide

Ή NMR (400 MHz, DMSO-i/6) δ ppm 8.67 (d, J=7.83 Hz, 1 H), 7.98 (dd, J=8.61, 5.48 Hz, 2 H), 7.52 (s, 1 H), 7.42 - 7.48 (m, 2 H), 7.28 (t, J=9.00 Hz, 2 H), 7.02 - 7.08 (m, 2 H), 5.12 - 5.18 (m, 1 H), 3.81 (s, 3 H), 2.68 - 2.74 (m, 2 H), 1.91 - 2.01 (m, 2 H), 1.71 - 1.80 (m, 2 H); Method 1, retention time: 2.867 min; HRMS: m/z (M+H)⁺ = 366.1606 (Calculated for C₂iH₂iFN₃0₂ = 366.1612).

[0370] NCGC00273439 (LLI09-079)

N-(l-(4-methoxyphenyl)-4,5,6,7-tetrahydro-lH-indazol-4-yl)-3,4-dimethylbenzamide

1H NMR (400 MHz, DMSO- 6) δ ppm 8.48 (d, J=7.83 Hz, 1 H), 7.71 (d, J=1.57 Hz, 1 H), 7.63 (dd, J=7.83, 1.96 Hz, 1 H), 7.49 (s, 1 H), 7.42 - 7.48 (m, 2 H), 7.19 (d, J=7.83 Hz, 1 H), 7.02 - 7.08 (m, 2 H), 5.1 1 - 5.18 (m, 1 H), 3.81 (s, 3 H), 2.67 - 2.73 (m, 2 H), 2.25 (s, 6 H), 1.91 - 2.01 (m, 2 H), 1.71 - 1.80 (m, 2 H); Method 1, retention time: 3.040 min; HRMS: m/z (M+H)⁺ = 376.2010 (Calculated for C₂3H₂₆N3O₂ = 376.2020).

[0371] NCGC00273453 (LLI09-080)

3-Chloro-4-fluoro-N-(l-(4-methoxyphenyl)-4,5,6,7-tetrahydro-lH-indazol-4- yl)benzamide

H NMR (400 MHz, DMSO- 6) δ ppm 8.79 (d, J=7.83 Hz, 1 H), 8.15 (dd, J=7.24, 2.15 Hz, 1 H), 7.94 (ddd, J=8.61 , 4.89, 2.15 Hz, 1 H), 7.49 - 7.55 (m, 2 H), 7.43 - 7.48 (m, 2 H), 7.03 - 7.08 (m, 2 H), 5.1 1 - 5.17 (m, 1 H), 3.81 (s, 3 H), 2.70 (t, J=4.70 Hz, 2 H), 1.92 - 2.00 (m, 2 H), 1.73 -

1.80 (m, 2 H); Method 1 , retention time: 3.063 min; HRMS: m/z (M+H)⁺ = 400.1212

(Calculated for C21H20CIFN3O2 = 400.1223).

[0372] NCGC00273454 (LLI09-081 )

3-Chloro-N-(l-(4-methoxyphenyl)-4,5,6,7-tetrahydro-lH-indazol-4-yl)benzamide

Ή NMR (400 MHz, DMSO- 6) 5 ppm 8.77 (d, J=7.83 Hz, 1 H), 7.96 (t, J=1.76 Hz, 1 H), 7.87 (dt, J=7.73, 1.22 Hz, 1 H), 7.56 - 7.62 (m, 1 H), 7.53 (s, 1 H), 7.42 - 7.52 (m, 3 H), 7.02 - 7.09 (m, 2 H), 5.12 - 5.19 (m, 1 H), 3.81 (s, 3 H), 2.68 - 2.74 (m, 2 H), 1.96 (dq, J=10.27, 5.05 Hz, 2 H), 1.73 - 1.80 (m, 2 H); Method 1, retention time: 3.011 min; HRMS: m/z (M+Na)⁺ = 404.1 1 17 (Calculated for C₂iH₂₀ClN₃NaO2 = 404.1 136).

[0373] NCGC00273455 (LLI09-082)

3,4-Dichloro-N-(l-(4-methoxyphenyl)-4,5,6,7-tetrahydro-lH-indazol-4-yl)benzamide

Ή NMR (400 MHz, DMSO-c/6) 6 ppm 8.84 (d, J=7.83 Hz, 1 H), 8.16 (d, J=1.96 Hz, 1 H), 7.86 - 7.92 (m, 1 H), 7.72 - 7.77 (m, 1 H), 7.54 (s, 1 H), 7.41 - 7.48 (m, 2 H), 7.02 - 7.08 (m, 2 H), 5.1 1 - 5.18 (m, 1 H), 3.81 (s, 3 H), 2.70 (br. s., 2 H), 1.91 - 2.00 (m, 2 H), 1.72 - 1.81 (m, 2 H); Method 1 , retention time: 3.172 min; HRMS: m/z (M+H)⁺ = 416.0914 (Calculated for C21 H20CI2N3O2 = 416.0927).

[0374] NCGC00273456 (LLI09-083)

3-Acetamido-N-(l-(4-methoxyphenyl)-4,5,6,7-tetrahydro-lH-indazol-4-yl)benzamide

Ή NMR (400 MHz, DMSO- 6) δ ppm 10.04 (s, 1 H), 8.58 (d, J=7.83 Hz, 1 H), 8.00 (t, J=1.76 Hz, 1 H), 7.77 (dd, J=8.02, 1.37 Hz, 1 H), 7.54 (d, J=8.22 Hz, 1 H), 7.50 (s, 1 H), 7.42 - 7.48 (m, 2 H), 7.34 (t, J=7.83 Hz, 1 H), 7.02 - 7.08 (m, 2 H), 5.1 1 - 5.18 (m, 1 H), 3.81 (s, 3 H), 2.67 - 2.74 (m, 2 H), 2.05 (s, 3 H), 1.91 - 2.00 (m, 2 H), 1.72 - 1.80 (m, 2 H);

Method 1, retention time: 2.570 min; HRMS: m/z (M+H)⁺ = 405.1911 (Calculated for C₂₃H₂₅N₄0₃ = 405.1921).

[0375] NCGC00273457 (LLI09-084)

4-Chloro-N-(l-(4-methoxyphenyl)-4,5,6,7-tetrahydro-lH-indazol-4-yl)benzamide

Ή NMR (400 MHz, DMSO-i/6) δ ppm 8.72 (d, J=7.83 Hz, 1 H), 7.90 - 7.95 (m, 2 H), 7.49 - 7.55 (m, 3 H), 7.42 - 7.47 (m, 2 H), 7.02 - 7.08 (m, 2 H), 5.12 - 5.18 (m, 1 H), 3.81 (s, 3 H), 2.67 - 2.74 (m, 2 H), 1.93 - 2.01 (m, 2 H), 1.72 - 1.80 (m, 2 H); Method 1 , retention time: 2.992 min; HRMS: m/z (M+Na)⁺ = 404.1 1 19 (Calculated for C₂iH₂oClN₃Na0₂ = 404.1 136).

[0376] NCGC00273423 (LLI09-085)

4-Chloro-2-fluoro-N-(l-(4-methoxyphenyl)-4,5,6,7-tetrahydro-lH-indazol-4- yl)benzamide

1H NMR (400 MHz, DMSO-76) δ ppm 8.64 (d, 7=7.83 Hz, 1 H), 7.62 (t, 7=8.02 Hz, 1 H), 7.54 (s, 1 H), 7.51 (dd, 7=10.17, 1.96 Hz, 1 H), 7.41 - 7.47 (m, 2 H), 7.36 (dd, 7=8.41 , 1.76 Hz, 1 H), 7.02 - 7.07 (m, 2 H), 5.06 - 5.12 (m, 1 H), 3.80 (s, 3 H), 2.68 (t, 7=5.87 Hz, 2 H), 1.90 - 1.98 (m, 2 H), 1.75 (td, 2 H); Method 1 , retention time: 3.064 min; HRMS: m/z (M+H)⁺ = 400.1217 (Calculated for C₂iH₂₀ClFN₃O₂ = 400.1223).

[0377] NCGC00273507 (LLI09-088)

2-Fluoro-N-(l-(4-methoxyphenyl)-4,5,6,7-tetrahydro-lH-indazol-4-yl)benzamide

Ή NMR (400 MHz, DMSO-76) δ ppm 8.57 (d, 7=7.83 Hz, 1 H), 7.59 (td, 7=7.43, 1.96 Hz, 1 H), 7.42 - 7.55 (m, 4 H), 7.22 - 7.29 (m, 2 H), 7.02 - 7.07 (m, 2 H), 5.07 - 5.14 (m, 1 H), 3.80 (s, 3 H), 2.65 - 2.71 (m, 2 H), 1.91 - 1.99 (m, 2 H), 1.71 - 1.79 (m, 2 H); Method 1 , retention time: 2.915 min; HRMS: m/z (M+H)⁺ = 366.1606 (Calculated for C21H21 FN3O2 = 366.1612).

[0378] NCGC00273502 (LLI09-089)

N-(l-(4-methoxyphenyl)-4,5,6,7-tetrahydro-lH-indazol-4-yl)-3-methylbenzamide

1H NMR (400 MHz, DMSO-i 6) δ ppm 8.57 (d, J=7.83 Hz, 1 H), 7.74 (s, 1 H), 7.69 (td, J=4.40, 1.76 Hz, 1 H), 7.50 (s, 1 H), 7.42 - 7.48 (m, 2 H), 7.32 (d, J=5.09 Hz, 2 H), 7.02 - 7.08 (m, 2 H), 5.10 - 5.20 (m, 1 H), 3.81 (s, 3 H), 2.67 - 2.74 (m, 2 H), 2.35 (s, 3 H), 1.90 - 2.01 (m, 2 H), 1.71 -

1.81 (m, 2 H); Method 1 , retention time: 2.987 min; HRMS: m/z (M+H)⁺ = 362.1845 (Calculated for C₂₂H2₄N₃0₂ = 362.1863).

[0379] NCGC00273503 (LLI09-090)

3-Fluoro-N-(l-(4-methoxyphenyl)-4,5,6,7-tetrahydro-lH-indazoI-4-yI)benzamide

Ή NMR (400 MHz, DMSO- 6) δ ppm 8.74 (d, J=7.83 Hz, 1 H), 7.77 (d, J=7.83 Hz, 1 H), 7.68 - 7.74 (m, 1 H), 7.42 - 7.55 (m, 4 H), 7.37 (td, J-8.41 , 2.35 Hz, 1 H), 7.02 - 7.09 (m, 2 H), 5.12 - 5.20 (m, 1 H), 3.81 (s, 3 H), 2.67 - 2.74 (m, 2 H), 1.91 - 2.02 (m, 2 H), 1.72 - 1.81 (m, 2 H); Method 1 , retention time: 2.944 min; HRMS: m/z (M+H)⁺ = 366.1610 (Calculated for C21 H21 FN3O2 = 366.1612).

[0380] NCGC00273504 (LLI09-091)

N-(l-(4-methoxyphenyl)-4,5,6,7-tetrahydro-lH-indazol-4-yl)-4-methylbenzamide

Ή NMR (400 MHz, DMSO- 6) δ ppm 8.54 (dd, J=8.41 , 0.98 Hz, 1 H), 7.81 (d, J=8.22 Hz, 2 H), 7.50 (s, 1 H), 7.42 - 7.48 (m, 2 H), 7.25 (d, J=8.22 Hz, 2 H), 7.02 - 7.08 (m, 2 H), 5.12 - 5.19 (m, 1 H), 3.81 (s, 3 H), 2.66 - 2.73 (m, 2 H), 2.35 (s, 3 H), 1.96 (dt, J=l 1.05, 4.65 Hz, 2 H), 1.70 - 1.79 (m, 2 H); Method 1 , retention time: 2.981 min; HRMS: m/z (M+H)⁺ = 362.1848 (Calculated for C₂₂H₂₄N₃0₂= 362.1863).

[0381] NCGC00274028 (LLI10-021)

3-chloro-N-(l-(4-methoxyphenyl)-4,5,6,7-tetrahydro-lH-indazol-4-yl)picolinamide

Ή NMR (400 MHz, DMSO- 6) 5 ppm 8.82 (d, J-8.22 Hz, 1 H), 8.52 (dd, J=4.70, 1.17 Hz, 1 H), 7.98 - 8.04 (m, 1 H), 7.54 (s, 1 H), 7.51 (dd, J=8.22, 4.70 Hz, 1 H), 7.41 - 7.47 (m, 2 H), 7.02 - 7.08 (m, 2 H), 5.08 - 5.15 (m, 1 H), 3.80 (s, 3 H), 2.65 - 2.72 (m, 2 H), 1.92 - 1.99 (m, 2 H), 1.74 - 1.81 (m, 2 H); Method 1 , retention time: 3.357 min; HRMS: m/z (M+H)⁺ = 383.1256 (Calculated for

383.1269).

[0382] NCGC00274150 (LLI10-029)

4-(3-(2H-tetrazol-5-yl)benzyl)-N-(3,4-diethoxyphenethyl)-4H-thieno[3,2-b]pyrrole-5- carboxamide

^!H NMR (400 MHz, DMSO-d6) δ ppm 8.34 (t, J=5.67 Hz, 1 H), 7.92 (s, 1 H), 7.87 (dt, J=7.83, 1.37 Hz, 1 H), 7.50 (t, J=7.83 Hz, 1 H), 7.44 (d, J=5.09 Hz, 1 H), 7.27 (d, J=8.22 Hz, 1 H), 7.20 (d, J=5.48 Hz, 1 H), 7.13 (s, 1 H), 6.75 - 6.79 (m, 2 H), 6.65 (dd, J=8.22, 1.96 Hz, 1 H), 5.89 (s, 2 H), 3.94 (qd, J=7.04, 1.17 Hz, 4 H), 3.35 - 3.43 (m, 2 H), 2.70 (t, J=7.24 Hz, 2 H), 1.27 (dt, J=10.17, 7.04 Hz, 6 H); Method 1 , retention time: 2.582 min; HRMS: m/z (M+H)⁺ = 517.1994 (Calculated for C₂₇H₂₉N₆0₃S = 517.2016).

-031)

tert-Butyl 2-(2-(2-(5-(3-((5-(3,4-diethoxyphenethylcarbamoyI)-4H-thieno[3,2-b]pyrrol-4- yl)methyl)phenyl)-2H-tetrazol-2-yl)ethoxy)ethoxy)ethylcarbamate

1H NMR (400 MHz, CHLOROFORM-d) 5 ppm 7.98 - 8.06 (m, 2 H), 7.37 (t, J=7.83 Hz, 1 H), 7.17 - 7.24 (m, 2 H), 6.85 (d, J=4.70 Hz, 1 H), 6.81 (d, J=8.22 Hz, 1 H), 6.67 - 6.75 (m, 3 H), 6.18 (t, J=5.87 Hz, 1 H), 5.84 (s, 2 H), 5.01 (br. s., 1 H), 4.80 (t, J=5.48 Hz, 2 H), 3.99 - 4.10 (m, 6 H), 3.56 - 3.64 (m, 4 H), 3.49 - 3.55 (m, 2 H), 3.44 (t, J=5.09 Hz, 2 H), 3.24 (q, J=4.83 Hz, 2 H), 2.80 (t, J=6.85 Hz, 2 H), 1.36 - 1.49 (m, 15 H); Method 1 , retention time: 3.055 min; HRMS: m/z (M+H)⁺ = 748.3484 (Calculated for C₃₈H₅₀N₇O₇S = 748.3487).

[0384] NCGC00274153 (LLI10-032)

tert-Butyl 2-(2-(2-(5-(4-((5-(3,4-diethoxyphenethylcarbamoyl)-4H-thieno[3,2-b]pyrrol-4- yl)methyl)phenyl)-2H-tetrazoI-2-yl)ethoxy)ethoxy)ethylcarbamate

Ή NMR (400 MHz, DMSO-c/6) δ ppm 8.33 (t, J=5.67 Hz, 1 H), 7.96 (d, J=8.22 Hz, 2 H), 7.44 (d, J=5.48 Hz, 1 H), 7.29 (d, J=8.22 Hz, 2 H), 7.18 (d, J=5.48 Hz, 1 H), 7.12 (s, 1 H), 6.77 - 6.83 (m, 2 H), 6.63 - 6.72 (m, 2 H), 5.86 (s, 2 H), 4.87 (t, J=5.09 Hz, 2 H), 3.89 - 4.02 (m, 6 H), 3.47 - 3.53 (m, 2 H), 3.38 - 3.44 (m, 4 H), 3.29 (t, J=6.06 Hz, 2 H), 2.99 (q, J=5.87 Hz, 2 H), 2.72 (t, J=7.04 Hz, 2 H), 1.34 (s, 9 H), 1.26 (dt, J=9.00, 7.04 Hz, 6 H); Method 1 , retention time: 3.034 min; HRMS: m/z (M+H)⁺ = 748.3462 (Calculated for. C₃8H₅0N₇O₇S = 748.3487).

[0385] NCGC00274164 (LLI 10-047)

ethyl l-(2-(3-(4-(l-(2-(2-(2-(2-aminoethoxy)ethoxy)ethoxy)ethyl)-lH-l,2,3-triazol-4- yl)phenyl)ureido)-2-methylpropanoyl)piperidine-4-carboxylate

1H NMR (400 MHz, DMSO- 6) δ ppm 8.46 - 8.53 (m, 1 H), 8.35 - 8.42 (m, 1 H), 7.63 - 7.76 (m, 4 H), 7.42 (dd, J=8.61, 2.74 Hz, 2 H), 6.70 - 6.77 (m, 1 H), 4.54 (d, J=5.09 Hz, 2 H), 4.28 - 4.39 (m, 2 H), 3.94 - 4.04 (m, 2 H), 3.82 - 3.90 (m, 2 H), 3.46 - 3.60 (m, 9 H), 2.87 - 2.99 (m, 4 H), 1.77 (d, J=12.52 Hz, 2 H), 1.35 - 1.47 (m, 9 H), 1.04 - 1.13 (m, 4 H); Method 1 , retention time: 1.502 min; HRMS: m/z (M+H)⁺ = 604.3452 (Calculated for C₂₉H4₆N₇07 = 604.3453).

[0386] NCGC00274165 (LLI 10-048)

ethyl l-(2-(3-(3-(l-(2-(2-(2-(2-aminoethoxy)ethoxy)ethoxy)ethyl)-lH-l,2,3-triazol-4- yl)phenyl)ureido)-2-methylpropanoyl)piperidine-4-carboxylate Ή NMR (400 MHz, DMSO- 6) δ ppm 8.52 (s, 1 H), 8.44 (s, 1 H), 7.97 (t, J=1.76 Hz, 1 H), 7.71 (br. s., 2 H), 7.33 - 7.38 (m, 1 H), 7.28 (t, J=7.83 Hz, 1 H), 7.20 (dt, J=8.22, 1.57 Hz, 1 H), 6.72 (s, 1 H), 4.57 (t, J=5.28 Hz, 2 H), 4.34 (d, J=13.30 Hz, 2 H), 3.98 (q, J=7.04 Hz, 2 H), 3.88 (t, J=5.28 Hz, 2 H), 3.47 - 3.59 (m, 1 1 H), 2.91 - 2.99 (m, 3 H), 1.78 (dd, J=12.72, 2.54 Hz, 2 H), 1.37 - 1.48 (m, 9 H), 1.08 (t, J=7.24 Hz, 3 H); Method 1, retention time: 1.529 min; HRMS: m/z (M+H)⁺ = 604.3456 (Calculated for C₂₉H₄₆N₇0₇ = 604.3453).

[0387] NCGC00318985 (LLI10-050)

tert-butyl 2-(2-(2-(4-(4-(2-(dimethylamino)acetamido)-4,5,6,7-tetrahydro-lH-indazol-l- yl)phenoxy)ethoxy)ethoxy)ethylcarbamate

Ή NMR (400 MHz, DMSO- 6) δ ppm 8.83 (d, J=7.83 Hz, 1 H), 7.52 (s, 1 H), 7.38 - 7.46 (m, 2 H), 7.02 - 7.10 (m, 2 H), 6.76 (t, J=5.87 Hz, 1 H), 4.93 - 5.02 (m, 1 H), 4.10 - 4.18 (m, 2 H), 3.89 (br. s., 2 H), 3.72 - 3.79 (m, 2 H), 3.56 - 3.63 (m, 2 H), 3.49 - 3.56 (m, 2 H), 3.06 (q, J=6.00 Hz, 2H), 2.83 (s, 6 H), 2.69 (t, J=6.26 Hz, 2 H), 1.72 - 1.97 (m, 4 H), 1.61 - 1.72 (m, 2 H), 1.36 (s, 9 H); Method 1 , retention time: 4.170 min; HRMS: m/z (M+H)⁺ = 546.3286 (Calculated for C₂₈H₄₄N₅0₆ = 546.3286).

[0388] NCGC00344516 (LLI 1 1 -041)

4-(3-(2-(2-(2-(2-aminoethoxy)ethoxy)ethyl)-2H-tetrazol-5-yl)benzyl)-N-(3,4- diethoxyphenethyl)-4H-thieno [3,2-b] pyrrole-5-carboxamide

1H NMR (400 MHz, DMSO-t 6) δ ppm 8.36 (t, J=5.67 Hz, 1 H), 7.89 - 7.95 (m, 2 H), 7.70 (br. s., 2 H), 7.43 - 7.50 (m, 2 H), 7.27 (d, J=7.83 Hz, 1 H), 7.19 (d, J=5.09 Hz, 1 H), 7.13 (s, 1 H), 6.80 (d, J=8.22 Hz, 1 H), 6.78 (d, J=l .96 Hz, 1 H), 6.66 (dd, J=8.22, 1.96 Hz, 1 H), 5.89 (s, 2 H), 4.87 (t, J=5.28 Hz, 2 H), 3.90 - 4.00 (m, 6 H), 3.51 - 3.56 (m, 2 H), 3.45 - 3.51 (m, 4 H), 3.36 - 3.43 (m, 2 H), 2.90 (t, J=5.28 Hz, 2 H), 2.72 (t, J=7.24 Hz, 2 H), 1.22 - 1.32 (m, 6 H); Method 1 , retention time: 2.283 min; HRMS: m/z (M+H)⁺ = 648.2954 (Calculated for C₃₃H4₂N₇0₅S - 648.2963).

[0389] NCGC00344517 (LLI 1 1 -042)

4-(4-(2-(2-(2-(2-aminoethoxy)ethoxy)ethyl)-2H-tetrazol-5-yl)benzyl)-N-(4- methoxyphenethyl)-4H-thieno [3,2-b] pyrrole-5-carboxamide

1H NMR (400 MHz, DMSO- 6) δ ppm 8.36 (t, J=5.67 Hz, 1 H), 7.97 (d, J=8.22 Hz, 2 H), 7.72 (br. s., 2 H), 7.44 (d, J=5.48 Hz, 1 H), 7.29 (d, J=8.22 Hz, 2 H), 7.18 (d, J=5.48 Hz, 1 H), 7.07 - 7.14 (m, 3 H), 6.82 (d, J=8.22 Hz, 2 H), 5.86 (s, 2 H), 4.89 (t, J=5.09 Hz, 2 H), 3.99 (t, J=5.09 Hz, 2 H), 3.69 (s, 3 H), 3.52 - 3.57 (m, 2 H), 3.46 - 3.51 (m, 4 H), 3.36 - 3.43 (m, 2 H), 2.89 (d, J=1.17 Hz, 2 H), 2.74 (t, J=7.43 Hz, 2 H); Method 1, retention time: 2.165 min; HRMS: m/z (M+H)⁺ = 590.2540 (Calculated for C₃₀H₃₆N₇O₄S = 590.2544).

-082

4-benzyl-N-(3,4-diethoxy-2-fluorophenethyl)-4H-thieno[3,2-b]pyrroIe-5-carboxamide

Ή NMR (400 MHz, DMSO-i/6) δ ppm 8.35 (t, J= 5.8 Hz, 1H), 7.41 (d, J = 5.3 Hz, 1H), 7.30 - 7.17 (m, 3H), 7.16 - 7.1 1 (m, 3H), 7.06 (d, J= 0.6 Hz, 1H), 6.85 (t, J= 8.4 Hz, 1H), 6.74 (dd, J = 8.6, 1.5 Hz, 1 H), 5.77 (s, 2H), 4.00 (dq, J = 8.0, 7.0 Hz, 4H), 3.40 (dt, J= 7.4, 6.1 Hz, 2H), 2.80 - 2.73 (m, 2H), 1 .32 (t, J= 7.0 Hz, 3H), 1.26 - 1.20 (m, 3H). Method 1 , retention time: 6.992 min; HRMS: m/z (M+H)⁺ = 467.1799 (Calculated for C₂₆H₂8FN₂0₃S = 467.1799).

[0391] LLI1 1 -086

4-benzyl-N-(4,5-diethoxy-2-fluorophenethyl)-4H-thieno[3,2-b]pyrrole-5-carboxamide

1H NMR (400 MHz, DMSO- 6) 5 ppm 8.34 (t, J=5.67 Hz, 1 H) 7.41 (d, J=5.09 Hz, 1 H) 7.17 - 7.29 (m, 3 H) 7.1 1 - 7.16 (m, 3 H) 7.08 (s, 1 H) 6.78 - 6.84 (m, 2 H) 5.77 (s, 2 H) 3.98 (q, J=7.04 Hz, 2 H) 3.89 (q, J=6.91 Hz, 2 H) 3.41 (q, J=6.91 Hz, 2 H) 2.75 (t, J=7.24 Hz, 2 H) 1.30 (t, J=7.04 Hz, 3 H) 1.22 (t, 3 H)). Method 1, retention time: 6.868 min; HRMS: m/z (M+H)⁺ = 467.1809 (Calculated for C₂6H₂₈FN₂0₃S = 467.1799).

EXAMPLE 22

[0392] This example provides S3 lipid droplet data and 3T3 lipid droplet data exhibited by various embodiments of the invention. The results are set forth in Table 5. The compounds were classified in potency categories as follows: a = <0.1 mM; b = 0.1-1 mM; c = 1 -10 mM; d, 10-30 mM; e = >30 mM.

Table 5.

3T3-L1

S3 cells cells

Sample ID potency potency

category category

NCGC00263797-01 a e

NCGC00273466-01 a e

NCGC00273464-01 a e

NCGC00242549-01 a e

NCGC00242551 -01 a e

NCGC00242574-01 a e

NCGC00242575-01 a e

NCGC00244962-01 a e

NCGC00244964-01 a e NCGC00244964-02 a e

NCGC00244965-01 a e

NCGC00319089-01 a e

NCGCOOl 89332-01 a e

NCGC00242573-01 a e

NCGCOOl 89555-01 a e

NCGC00244462-01 a e

NCGC00273410-01 a e

NCGC00244966-01 a e

NCGC00242548-01 a e

NCGC00274028-01 a e

NCGC00238548-01 a e

NCGC00319088-01 a e

NCGC00273408-01 a b

NCGC00263792-01 a c

NCGC00263793-01 a e

NCGC00238539-01 a e

NCGC00253894-01 a e

NCGC00263803-01 a e

NCGC00238559-01 a e

NCGC00273465-01 a d

NCGC00273431-01 a e

NCGC00273507-01 a e

NCGC00273419-01 a e

NCGC00238548-02 a e

NCGC00238537-03 a e

NCGC00273434-01 a d

NCGC00273409-01 a e

NCGC00238537-01 a e

NCGC00273502-01 a d

NCGC00238537-02 a e

NCGC00273436-01 a e NCGC00273503-01 a e

NCGC00273504-01 a e

NCGC00273418-01 a e

NCGC00273407-01 a e

NCGC00273454-01 a e

NCGC00273443-01 a e

NCGC00273420-01 b e

NCGC00273435-01 b e

NCGC00238541-01 b e

NCGC00242572-01 b e

NCGC00273447-01 b e

NCGC00273438-01 b e

NCGC00273468-01 b e

NCGC00253902-01 b e

NCGC00253903-01 b e

NCGC00250253-01 b e

NCGC00273960-01 b

NCGC00273444-01 b e

NCGC00273467-01 b e

NCGC00242571-01 b c

NCGC00273437-01 b e

NCGC00238561-01 b e

NCGC00253898-01 b e

NCGC00273439-01 c c

NCGCOOl 89556-02 c e

NCGC00238547-01 c e

NCGC00253895-01 c e

NCGC00273453-01 c e

NCGC00273450-01 c e

NCGC00273451 -01 c e

NCGC00250256-01 c e

NCGC00238553-01 c e NCGC00273448-01 c e

NCGC00273469-01 c e

NCGC00244959-01 c e

NCGC00273423-01 c e

NCGC00273457-01 c e

NCGC00253899-01 c e

NCGC00238536-01 c e

NCGC00238556-01 c e

NCGC00253896-01 c e

NCGC00244963-01 c e

NCGC00238552-01 c e

NCGC00253908-01 c e

NCGC00253901-01 c e

NCGC00238557-01 c e

NCGC00263804-01 c e

NCGCOOl 89556-01 c e

NCGC00250264-01 c e

NCGC00238558-01 c d

NCGC00273449-01 c e

NCGC00241451-01 c e

NCGC00253897-01 c e

NCGC00253900-01 c e

NCGC00273456-01 d e

NCGC00263804-02 d e

NCGC00273452-01 d e

NCGC00238560-01 d e

NCGC00238554-01 d c

NCGC00238543-01 d e

NCGC00318985-01 d e

NCGC00250255-01 d

NCGC00273455-01 d e

NCGC00273402-01 d e NCGC00238555-01 e d

NCGC00274282-01 e e

NCGC00263805-01 e e

NCGC00238544-01 e e

NCGC00238545-01 e e

NCGC00241426-02 a a

NCGC00241429-01 a a

NCGC00263054-01 a a

NCGC00238551-01 a a

NCGC00241427-01 a b

NCGC00263048-01 a b

NCGC00241430-01 a a

NCGC00241424-01 a c

NCGC00263053-01 a

NCGC00241426-01 a

NCGC00241428-01 a

NCGC00238550-01 a a

NCGCOOl 12165-02 a

NCGC00274152-01 a b

NCGC00263067-01 b b

NCGC00241441-01 b c

NCGC00241425-01 b

NCGC00092589-02 b b

NCGC00263047-01 b b

NCGC00241431-01 b

NCGC00263787-01 b b

NCGC00263806-01 b c

NCGC00241434-01 b b

NCGC00253906-01 b b

NCGC00263034-01 b b

NCGC00241423-01 b e

NCGC00241435-01 c b NCGC00238538-01 c e

NCGC00241436-01 c c

NCGC00274153-01 c c

NCGC00241422-01 c b

NCGC00241445-01 c d

NCGC00253907-01 c e

NCGC00274150-01 c e

NCGC00263035-01 c a

NCGC00238546-01 c c

NCGC00241417-01 c c

NCGC00241453-01 c e

NCGC00238549-01 c e

NCGC00241437-01 c c

NCGC00241416-01 c e

NCGC00274151-01 c e

NCGC00241442-01 c c

NCGC00241438-01 c e

NCGC00263050-01 d e

NCGC00241452-01 d b

NCGC00241420-01 d b

NCGC00253905-01 d c

NCGC00241440-01 d c

NCGC00263033-01 d c

NCGC00241415-01 d e

NCGC00263052-01 d c

NCGC00241443-01 d c

NCGC00262861 -01 d e

NCGC00263030-01 e c

NCGC00263049-01 e c

NCGC00263051 -01 e c

NCGC00241432-01 e

NCGC00263278-01 e e NCGC00241444-01 e e

NCGC00241414-01 e e

NCGC00238540-01 e e

NCGC00241006-01 e e

NCGC00241007-01 e e

NCGC00241413-01 e e

NCGC00241419-01 e e

NCGC00241421-01 e e

NCGC00241433-01 e e

NCGC00241439-01 e e

NCGC00241418-01 e e

NCGC00242556-01 a

NCGC00242555-01 a e

NCGC00241450-01 b c

NCGC00250263-01 b e

NCGC00241448-01 b c

NCGC00238542-01 b c

NCGC00242560-01 b c

NCGC00242568-01 b e

NCGC00241447-01 b c

NCGC00034917-03 b e

NCGC00242552-01 c d

NCGC00250259-01 c e

NCGC00241446-01 c e

NCGC00242564-01 c e

NCGC00250262-01 c e

NCGC00242553-01 c e

NCGC00242566-01 c e

NCGC00242554-01 c e

NCGC00242559-01 c e

NCGC00242567-01 c e

NCGC00250258-01 c NCGC00242565-01 c e

NCGC00242569-01 c e

NCGC00242563-01 c e

NCGC00242550-01 c e

NCGC00242561-01 d e

NCGC00253904-01 d c

NCGC00242557-01 d

NCGC00242564-02 d e

NCGC00242558-01 d e

NCGC00244961 -01 d e

NCGC00242563-02 d e

NCGC00241449-01 e e

NCGC00242562-01 e e

NCGC00242570-01 e e

NCGC00274164-01 e e

NCGC00274165-01 e e

NCGC00244960-01 e e

[0393] All references, including publications, patent applications, and patents, cited herein are hereby incorporated by reference to the same extent as if each reference were individually and specifically indicated to be incorporated by reference and were set forth in its entirety herein.

[0394] The use of the terms "a" and "an" and "the" and similar referents in the context of describing the invention (especially in the context of the following claims) are to be construed to cover both the singular and the plural, unless otherwise indicated herein or clearly contradicted by context. The terms "comprising," "having," "including," and "containing" are to be construed as open-ended terms (i.e., meaning "including, but not limited to,") unless otherwise noted. Recitation of ranges of values herein are merely intended to serve as a shorthand method of referring individually to each separate value falling within the range, unless otherwise indicated herein, and each separate value is incorporated into the specification as if it were individually recited herein. All methods described herein can be performed in any suitable order unless otherwise indicated herein or otherwise clearly contradicted by context. The use of any and all examples, or exemplary language (e.g., "such as") provided herein, is intended merely to better illuminate the invention and does not pose a limitation on the scope of the invention unless otherwise claimed. No language in the specification should be construed as indicating any non-claimed element as essential to the practice of the invention.

[0395] Preferred embodiments of this invention are described herein, including the best mode known to the inventors for carrying out the invention. Variations of those preferred embodiments may become apparent to those of ordinary skill in the art upon reading the foregoing description. The inventors expect skilled artisans to employ such variations as appropriate, and the inventors intend for the invention to be practiced otherwise than as specifically described herein. Accordingly, this invention includes all modifications and equivalents of the subject matter recited in the claims appended hereto as permitted by applicable law. Moreover, any combination of the above-described elements in all possible variations thereof is encompassed by the invention unless otherwise indicated herein or otherwise clearly contradicted by context.

Claims

CLAIM(S):

1. A compound of formula I, II, or III:

I I I I I

wherein:

R is selected from heterocyclyl, heteroaryl, cycloalkyl, dimethylamino alkyl,

R^{! 0} is selected from alkyl, dialkylaminoalkyl, heterocyclyl, heteroaryl, heteroarylalkyl, aryl, arylalkyl, (3-(trifluoromethyl)-3H-diazirin-3-yl), arylcycloalkyl, and each of which is optionally substituted with one or more substituents selected from alkyl, alkenyl, halo, cycloalkyl, aryl, fused aryl, fused cyclic, arylalkyl, heteroarylalkyl, and arylcarbonyl;

R ^{1 1} , R^{1 2}, R ¹³, and R¹⁴ are independently hydrogen or alkyl;

R⁶ and R⁷ are independently hydrogen,lower alkyl, or arylalkyloxyalkyl, or, taken together with the carbon atom to which they are bonded, form a 3-7 membered ring; R is H or a substituent selected from halo, alkyl, monohalo alkyl, dihaloalkyl, trihaloalkyl, monohalo alkoxy, dihalo alkoxy, trihalo alkoxy, hydroxy, carboxy, phosphoryl, phosphonyl, phosphono alkyl, carboxy alkyl, dicarboxy alkyl, dicarboxy haloalkyl, sulfonyl, cyano, nitro, alkoxy, alkoxy carbonyl, heterocyclyl, alkyl heterocyclyl, heterocyclylalkyl, alkylthio, acyl, acyloxy, thioacyl, acylthio, aryloxy, amino, aminoalkyl, alkylamino, dialkylamino,

R is hydrogen or lower alkyl;

R¹⁹ is hydrogen or halo;

A is NH(CH₂)_m, CH₂, or a bond; m is 0 or 1 ; n is 1-5; and p is 0-1 ; a pharmaceutically acceptable salt thereof, or an enantiomer thereof; or a conjugate thereof wherein the conjugate comprises a marker group; with the proviso that, in the compound of formula I, when R¹ is 4-t-butylphenyl,

3,5-dimethylphenyl, 4-methoxyphenyl, 3-trifluoromethylphenyl, 4-trifluoromethylphenyl or 4-bromophenyl, then R is not furazan-4-yl, 4-methylfurazan-5-yl, furazan-4-yl-N-oxide, isoxazol-5-yl, 3-methylisoxazol-4-yl, pyrazin-2-yl, or 3-hydroxypyridin-2-yl.

2. The compound, salt, enantiomer, or conjugate of claim 1 , wherein the compound is of formula I, wherein R^J is aryl, optionally substituted with one or more substituents selected from halo and alkyl, and wherein A is NH..

3. The compound, salt, enantiomer, or conjugate of claim 2, wherein R¹ is phenyl, optionally substituted with one or more substituents selected from halo and alkyl.

4. The compound, salt, enantiomer, or conjugate of claim 3, wherein R¹ is phenyl, optionally substituted with one or more substituents selected from fluoro, methyl, and t-butyl.

5. The compound, salt, enantiomer, or conjugate of claim 2, wherein R² is selected from heterocyclyl, heteroaryl, cycloalkyl, dimethylamino alkyl, and benzyl, each of which is optionally substituted with one or more substituents selected from halo, hydroxy, carboxy, carboxy alkyl, dicarboxy alkyl, dicarboxy haloalkyl, alkoxy, alkylthio, acyl, acyloxy, thioacyl, acylthio, aryloxy, amino, aminoalkyl, alkylamino, dialkylamino, and trialkylamino.

6. The compound, salt, enantiomer, or conjugate of claim 5, wherein R² is selected from heterocyclyl, heteroaryl, cycloalkyl, dimethylamino alkyl, and benzyl, each of which is optionally substituted with hydroxy.

7. The compound, salt, enantiomer, or conjugate of claim 6, wherein R² is selected from pyrazinyl, dioxinyl, thiadiazolyl, oxazolinylmethyl, pyridinyl, phenyl, benzyl, piperidinyl, cyclopropyl, thiopheneyl, cyclohexyl, pyrazolyl, dimethylaminomethyl, N-protected piperidinyl, and oxadiazolyl, each of which is optionally substituted with hydroxy.

8. The compound, salt, enantiomer, or conjugate of claim 1 , wherein the compound is of formula II, wherein

arylcarbonyl;

Rⁿ, R¹², R¹³, and R¹⁴ are independently hydrogen or alkyl, R¹⁹ is hydrogen or halo, and p is 0-3.

9. The compound, salt, enantiomer, or conjugate of claim 8, wherein R¹⁰ is heteroaryl, optionally substituted with one or more substituents selected from alkyl, halo, cycloalkyl, aryl, fused aryl, fused cyclic, arylalkyl, and arylcarbonyl, wherein R^{1 1}, R¹², R¹³, and R¹⁴ are independently hydrogen or alkyl, wherein R¹⁸ is hydrogen or lower alkyl. wherein R¹⁹ is hydrogen or halo, and p is 0-3.

10. The compound, salt, enantiomer, or conjugate of claim 9 wherein R¹⁰ is

wherein R⁵ is selected from lower alkyl, alkenyl, aryl, arylalkyl, dialkylaminoalkyl, heterocyclyl, heteroaryl, heteroarylalkyl, and benzyl, each of which is optionally substituted with one or more substituents selected from alkyl, arylalkyl, heteroaryl alkyl,

heteroarylarylalkyl, alkenyl, and arylalkyl, wherein each of said optional substituents are further optionally substituted with one or more substituents selected from halo, alkyl, alkenyl, monohalo alkoxy, dihalo alkoxy, trihalo alkoxy, hydroxy, carboxy, carboxy alkyl, dicarboxy alkyl, dicarboxy haloalkyl, optionally protected aminopolyalkoxy, sulfonyl, cyano, nitro, alkoxy, alkylthio, acyl, acyloxy, thioacyl, acylthio, aryloxy, amino, aminoalkyl, alkylamino,

dialkylamino, trialkylamino, aminocarbonyl, aldehydo, and ureido.

1 1. The compound, salt, enantiomer, or conjugate of claim 10, wherein R³ and R⁴ are each independently ethyl or, taken together with the carbon atom to which they are attached, form a 5-membered ring.

12. The compound, salt, enantiomer, or conjugate of any one of claims 9-1 1, wherein R⁵ is selected from the group consisting of thiophenopyrrolyl, phenyl, thiopheneyl, benzyl, dimethylamino alkyl, alkyl, benzodioxanyl, and cyclopenta[£>]thiopheneyl, each of which is optionally substituted with one or more substituents selected from the group consisting of halo, alkyl, phenylalkyl, dihalo alkoxy, and pyridyl alkyl.

13. The compound, salt, enantiomer, or conjugate of claim 8, wherein R¹⁰ is selected from

alkyl, dialkylaminoalkyl, aryl, arylalkyl, arylcycloalkyl,

more substituents selected from alkyl, aryl, arylalkyl, arylcarbonyl, and halo.

14. The compound, salt, enantiomer, or conjugate of claim 1 , wherein the compound is of formula III, wherein R⁶ and R⁷ are independently lower alkyl or, taken together with the carbon atom to which they are bonded, form a 5-7 membered cycloalkyl ring;

R⁹ is H, OR¹⁵, or NR¹⁶R¹⁷; and n is 1-5.

15. The compound, salt, enantiomer, or conjugate of claim 14, wherein

R⁶ and R⁷ are individually lower alkyl or, taken together with the carbon atom to which they are bonded, form a 5-7 membered cycloalkyl ring;

R is H or a substituent selected from the group consisting of halo, cyano, alkoxy, monohalo alkyl, dihaloalkyl, trihaloalkyl, morpholino alkyl, benzo, fused thiopheno, alkyl thiazolyl, phenyl, aryloxy, alkoxycarbonyl, amino, aminoalkyl, alkylamino, dialkylamino, and trialkylamino;

R⁹ is OR¹⁵ is; and n is 1 or 2.

16. The compound, salt, enantiomer, or conjugate of claim 14, wherein

R⁹ is NR¹⁶R¹⁷; and n is 1 or 2.

17. A pharmaceutical composition comprising a compound, salt, enantiomer, or conjugate of any one of claims 1-16 and a pharmaceutically acceptable carrier.

18. A method of preventing or treating a disease or disorder responsive to reduction of lipid storage droplets in an animal in need thereof comprising administering an effective amount of a compound of formula I, II, or III or a combination thereof:

I II III

wherein:

R¹ is selected from alkyl, aryl, arylalkyl, and alkylaryl, each of which is optionally substituted with one or more substituents selected from halo, alkyl, hydroxy, hydroxyalkyl, carboxy, phosphoryl, phosphonyl, phosphono alkyl, carboxy alkyl, dicarboxy alkyl, dicarboxy haloalkyl, sulfonyl, cyano, nitro, alkoxy, trifluoroalkyl, trifluoroalkoxy, alkylthio, acyl, acyloxy, thioacyl, acylthio, aryloxy, amino, aminoalkyl, alkylamino, dialkylamino, trialkylamino, guanidino, aminocarbonyl, aldehydo, optionally protected aminopolyalkoxy, and ureido;

R is selected from heterocyclyl, heteroaryl, cycloalkyl, dimethylamino alkyl, and benzyl, each of which is optionally substituted with one or more substituents selected from halo, hydroxy, carboxy, phosphoryl, phosphonyl, phosphono alkyl, carboxy alkyl, dicarboxy alkyl, dicarboxy haloalkyl, sulfonyl, cyano, nitro, alkoxy, alkylthio, acyl, acyloxy, thioacyl, acylthio, aryloxy, amino, aminoalkyl, alkylamino, dialkylamino, trialkylamino, guanidino,

aminocarbonyl, aldehydo, and ureido;

R³ and R⁴ are each independently a lower alkyl or, taken together with the carbon atom to which they are attached, form a 3- to 7-membered ring;

R¹⁰ is selected from alkyl, dialkylaminoalkyl, heterocyclyl, heteroaryl, heteroarylalkyl, aryl, arylalkyl, arylcycloalkyl, and each of which is optionally substituted with one or more substituents selected from alkyl, alkenyl, halo, cycloalkyl, aryl, fused aryl, fused cyclic, arylalkyl, heteroarylalkyl, and arylcarbonyl;

R", R¹², R¹³, and R¹⁴ are independently hydrogen or alkyl; R° and R' are independently hydrogen,lower alkyl, or arylalkyloxyalkyl, or, taken together with the carbon atom to which they are bonded, form a 5-7 membered ring;

R is H or a substituent selected from halo, alkyl, monohalo alkyl, dihaloalkyl, tnhaloalkyl, monohalo alkoxy, dihalo alkoxy, trihalo alkoxy, hydroxy, carboxy, phosphoryl, phosphonyl, phosphono alkyl, carboxy alkyl, dicarboxy alkyl, dicarboxy haloalkyl, sulfonyl, cyano, nitro, alkoxy, alkoxy carbonyl, heterocyclyl, alkyl heterocyclyl, heterocyclylalkyl, alkylthio, acyl, acyloxy, thioacyl, acylthio, aryloxy, amino, aminoalkyl, alkylamino, dialkylamino,

R 18 is hydrogen or lower alkyl;

R¹⁹ is hydrogen or halo;

A is NH(CH₂)_m, CH₂, or a bond; m is 0 or 1 ; n is 1 -5; and p is 0-3; a pharmaceutically acceptable salt thereof, or an enantiomer thereof; or a conjugate thereof wherein the conjugate comprises a marker group; with the proviso that, in the compound of formula I, when R¹ is 4-t-butylphenyl,

3,5-dimethylphenyl, 4-methoxyphenyl, 3-trifluoromethylphenyl, 4-trifluoromethylphenyl or 4-bromophenyl, then R² is not furazan-4-yl, 4-methylfurazan-5-yl, furazan-4-yl-N-oxide, isoxazol-5-yl, 3-methylisoxazol-4-yl, pyrazin-2-yl, or 3-hydroxypyridin-2-yl.

19. The method of claim 18, wherein the compound is of formula I, wherein R¹ is aryl, optionally substituted with one or more substituents selected from halo and alkyl, and wherein A is NH.

20. The method of claim 19, wherein R¹ is phenyl, optionally substituted with one or more substituents selected from halo and alkyl.

21. The method of claim 20, wherein R¹ is phenyl, optionally substituted with one or more substituents selected from fluoro, methyl, and t-butyl.

22. The method of claim 19, wherein R² is selected from heterocyclyl, heteroaryl, cycloalkyl, dimethylamino alkyl, and benzyl, each of which is optionally substituted with one or more substituents selected from halo, hydroxy, carboxy, carboxy alkyl, dicarboxy alkyl, dicarboxy haloalkyl, alkoxy, alkylthio, acyl, acyloxy, thioacyl, acylthio, aryloxy, amino, aminoalkyl, alkylamino, dialkylamino, and trialkylamino.

23. The method of claim 22, wherein R² is selected from heterocyclyl, heteroaryl, cycloalkyl, dimethylamino alkyl, and benzyl, each of which is optionally substituted with hydroxy.

24. The method of claim 23, wherein R² is selected from pyrazinyl, dioxinyl, thiadiazolyl, oxazolinylmethyl, pyridinyl, phenyl, benzyl, piperidinyl, cyclopropyl, thiopheneyl, cyclohexyl, pyrazolyl, dimethylaminomethyl, N-protected piperidinyl, and oxadiazolyl, each of which is optionally substituted with hydroxy.

25. The method of claim 18, wherein the compound is of formula II, wherein

R¹⁰ is selected from alkyl, dialkylaminoalkyl, heterocyclyl, heteroaryl, aryl, arylalkyl, arylcycloalkyl, and each of which is optionally substituted with one or more substituents selected from alkyl, cycloalkyl, aryl, fused aryl, fused cyclic, arylalkyl, and arylcarbonyl;

R , R , R , and R ' are independently hydrogen or alkyl. R¹⁹ is hydrogen or halo, and p is 0-3.

26. The method of claim 25, wherein R¹⁰ is heteroaryl, optionally substituted with one or more substituents selected from alkyl, cycloalkyl, aryl, fused aryl, fused cyclic, arylalkyl, and arylcarbonyl, wherein R^{1 1} , R¹², R¹³, and R¹⁴ are independently hydrogen or alkyl, and wherein R¹⁸ is hydrogen or lower alkyl.

27. The method of claim 26 wherein R¹⁰ is

heteroarylarylalkyl, alkenyl, and arylalkyl, wherein each of said optional substituents are further optionally substituted with one or more substituents selected from halo, alkyl, monohalo alkoxy, dihalo alkoxy, trihalo alkoxy, hydroxy, carboxy, carboxy alkyl, dicarboxy alkyl, dicarboxy haloalkyl, optionally protected aminopolyalkoxy, sulfonyl, cyano, nitro, alkoxy, alkylthio, acyl, acyloxy, thioacyl, acylthio, aryloxy, amino, aminoalkyl, alkylamino,

dialkylamino, trialkylamino, aminocarbonyl, aldehydo, and ureido.

28. The method of claim 27, wherein R³ and R⁴ are each independently ethyl or, taken together with the carbon atom to which they are attached, form a 5-membered ring.

29. The method of any one of claims 26-28, wherein R⁵ is selected from the group consisting of thiophenopyrrolyl, phenyl, thiopheneyl, benzyl, dimethylamino alkyl, alkyl, benzodioxanyl, and cyclopenta[b]thiopheneyl, each of which is optionally substituted with one or more substituents selected from the group consisting of halo, alkyl, phenylalkyl, dihalo alkoxy, and pyridyl alkyl.

The method of claim 25, wherein R¹⁰ is selected from alkyl, dialkylamino, aryl,

31. The method of claim 18, wherein the compound is of formula III, wherein

R is H or a substituent selected from halo, alkyl, monohalo alkyl, dihaloalkyl, trihaloalkyl, cyano, nitro, alkoxy, heterocyclyl, alkyl heterocyclyl, heterocyclylalkyl, alkylthio, aryloxy, amino, aminoalkyl, alkylamino, dialkylamino, trialkylamino. R⁹ is H, OR¹⁵, or NR¹⁶R¹⁷; and n is 1-5.

32. The method of claim 31 , wherein

6 7

R° and R^; are individually lower alkyl or, taken together with the carbon atom to which they are bonded, form a 5-7 membered cycloalkyl ring;

R is H or a substituent selected from the group consisting of halo, cyano, alkoxy, monohalo alkyl, dihaloalkyl, trihaloalkyl, morpholino alkyl, benzo, fused thiopheno, alkyl thiazolyl, phenyl, aryloxy, alkoxycarbonyl, amino, aminoalkyl, alkylamino, dialkylamino, and trialkylamino; wherein R⁹ is R¹⁵; and n is 1 or 2.

33. The method of claim 31 , wherein

6 7

R° and R' are individually lower alkyl or, taken together with the carbon atom to which they are bonded, form a 5-7 membered cycloalkyl ring;

R⁹ is NR¹⁶R¹⁷; and n is 1 or 2.

34. The method of any one of claims 18-33, wherein the disease or disorder is selected from the group consisting of Gaucher disease, Fabry disease, Farber's disease, GM1 gangliosidoses, Tay-Sachs disease, Sandhoff disease, Krabbe disease, metachromatic leukodystrophy, obesity, atherosclerosis, and ectopic fat deposition.

35. A compound of any one of claims 1-16 or a composition of claim 17, for use in the prevention or treating of a disease or disorder responsive to reduction of lipid storage droplets in an animal in need thereof.

36. A compound of any one of claims 1-16 for use in identifying a molecular target involved in lipid storage in a cell, .

37. The compound of claim 36, wherein the compound is a conjugate thereof, wherein the conjugate comprises a marker group.

38. The compound of claim 37, wherein the market is a biotinylated moiety or a fluorescent moiety.