IP Library › Granted Patent US 9,884,868

Granted Patent B2

US 9,884,868 · App. 15/054,895 · Granted Feb 6, 2018

TGF-beta inhibitors

Inventors: Todd Kinsella (Redwood City, CA); Marina Gelman (San Francisco, CA); Hui Hong (Foster City, CA); Ihab S. Darwish (San Carlos, CA); Rajinder Singh (Belmont, CA); Jiaxin Yu (San Carlos, CA); Robert M. Borzilleri (New Hope, PA); Upender Velaparthi (Cheshire, CT); Peiying Liu (Madison, CT); Chetan Darne (Orange, CT); Hasibur Rahaman (Bangalore, IN); Jayakumar Sankara Warrier (Bangalore, IN)

Assignees: Rigel Pharmaceuticals, Inc.; Bristol-Myers Squibb Company

C07D487/04 C07D401/04 C07D403/04 C07D417/04 C07D471/04

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Quick Facts

Patent No.: US 9,884,868
App. No.: 15/054,895
Granted: Feb 6, 2018
Kind: B2

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Abstract

Disclosed are imidazole and thiazole compounds, as well as pharmaceutical compositions and methods of use thereof. One embodiment is a compound having the structure and pharmaceutically acceptable salts, prodrugs and N-oxides thereof (and solvates and hydrates thereof), wherein X, A, Z, R 1 and R′ are as described herein. In certain embodiments, a compound disclosed herein inhibits TGF-β, and can be used to treat disease by blocking TGF-β signaling.

Claims (712)

1. A compound having the structure of formula (I°),

or a pharmaceutically acceptable salt thereof,

wherein

X is —S— or —N(R′)—;

R′ is hydrogen, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkyloxy, —(C 0 -C 12 alkyl)-Cycloalkyl or —(C 0 -C 6 alkyl)-Heterocycloalkyl, each optionally substituted with 1 to 3 moieties that are each independently C 1 -C 6 alkyl, halogen, C 1 -C 6 haloalkyl, —OR S0 , C 1 -C 6 alkyl-OR S0′ , —C(O)OR S0 , —C(O)R S0 , —C(O)NR S0 2 , —R S0 or cyano;

wherein each R S0 is independently hydrogen, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, —(C 0 -C 6 alkyl)-Aryl, —(C 0 -C 6 alkyl)-Heteroaryl, —(C 0 -C 6 alkyl)-Cycloalkyl, or —(C 0 -C 6 alkyl)-Heterocycloalkyl, wherein Aryl, Heteroary, Cycloalkyl, Heterocycloalkyl, and haloalkyl are optionally substituted with C 1 -C 6 alkyl, halogen, C 1 -C 6 haloalkyl or cyano;

R 1 is hydrogen, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkyloxy, —OR S1 , —NR S1 2 , —SR S1 or —N(R S1 )C(O)R S1 , each optionally substituted with 1 to 3 moieties that are each independently C 1 -C 6 alkyl, halogen, C 1 -C 6 haloalkyl or cyano;

wherein each R S1 is independently hydrogen, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, —(C 0 -C 6 alkyl)-Aryl, —(C 0 -C 6 alkyl)-Heteroaryl, —(C 0 -C 6 alkyl)-Cycloalkyl, or —(C 0 -C 6 alkyl)-Heterocycloalkyl, wherein Aryl, Heteroary, Cycloalkyl, Heterocycloalkyl, alkyl, and haloalkyl are optionally substituted with C 1 -C 6 alkyl, halogen, C 1 -C 6 haloalkyl or cyano;

A′ is phenyl optionally substituted with one to five R 2 groups, wherein

each R 2 is independently halogen, —C 1 -C 6 alkyl, —C 1 -C 6 haloalkyl, —C 1 -C 6 alkoxy, —C 1 -C 6 haloalkoxy, —NO 2 , —N(R S2 )C(O)R S2 , —OR S2 , —C(O)NR S2 2 , —N(R S2 )S(O) 2 R S2 , —S(O) 2 R S2 , —(C 0 -C 6 alkyl)-Ar or —CN, wherein each alkyl, haloalkyl and alkoxy are optionally substituted with 1, 2, 3, or 4 groups that are each independently halogen, cyano, nitro, —OR S2 , —SR S2 , —NR S2 2 , —C(O)OR S2 , —C(O)NR S2 2 , —C(O)R S2 , —S(O)R S2 , —S(O) 2 R S2 , —S(O)OR S2 , —S(O) 2 OR S2 , —S(O)NR S2 2 , —S(O) 2 NR S2 2 , —OC(O)R S2 , —OC(O)OR S2 , —OC(O)NR S2 2 , —N(R S2 )C(O)R S2 , —N(R S2 )C(O)OR S2 , —N(R S2 )C(O)NR S2 2 , —N(R S2 )S(O)R S2 , —N(R S2 )S(O) 2 R S2 , C 1 -C 6 alkyl, or C 1 -C 6 haloalkyl;

wherein each R S2 is independently hydrogen, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, —(C 0 -C 6 alkyl)-Aryl, —(C 0 -C 6 alkyl)-Heteroaryl, —(C 0 -C 6 alkyl)-Cycloalkyl, or —(C 0 -C 6 alkyl)-Heterocycloalkyl, wherein Aryl, Heteroaryl, Cycloalkyl, Heterocycloalkyl, alkyl, and haloalkyl are optionally substituted with C 1 -C 6 alkyl, halogen, C 1 -C 6 haloalkyl or cyano;

Z is

a fused bicyclic ring of the formula,

wherein

ring A is Ar or 5- or 6-membered Heteroaryl,

ring B is 5- or 6-membered Heteroaryl,

wherein

Z is optionally substituted by one or two —R Z groups that are each independently halogen, cyano, C 1-6 alkyl, C 1-6 alkenyl, C 1-6 haloalkyl, —C 1 -C 6 alkoxy, —(C 0 -C 6 alkyl)-Heteroaryl, —(C 0 -C 6 alkyl)-Heterocycloalkyl, —OR S3 , —SR S3 , —NR S3 2 , —C(O)R S3 , —C(O)OR S3 , —C(O)NR S3 2 , —C(NR S3 )NR S3 OR S3 , —S(O) 2 NR S3 2 , —S(O) 2 R S3 , —OC(O)R S3 , —N(R S3 )C(O)R S3 , —OC(O)OR S3 , —OC(O)NR S3 2 , —N(R S3 )C(O)OR S3 , —N(R S3 )C(O)NR S3 2 , —N(R S3f )S(O) 2 R S3 , —OP(O)(OR S3 ) 2 or —CH 2 —OP(O)(OR S3 ), wherein each alkyl, haloalkyl and alkoxy is optionally substituted by one or two —R Z2 groups;

wherein each R S3 is independently hydrogen, —NR S3 2 , —OR S3 , C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, —(C 0 -C 6 alkyl)-Aryl, —(C 0 -C 6 alkyl)-Heteroaryl, —(C 0 -C 6 alkyl)-Cycloalkyl, or —(C 0 -C 6 alkyl)-Heterocycloalkyl, wherein Aryl, Heteroaryl, Cycloalkyl, Heterocycloalkyl, alkyl, and haloalkyl are optionally substituted with C 1 -C 6 alkyl, halogen, C 1 -C 6 haloalkyl, —C(O)NR S4 2 or cyano; and

each —R Z2 is independently halogen, cyano, C 1-6 alkyl, C 1-6 haloalkyl, —C 1 -C 6 alkoxy, —OR S4 , —SR S4 , —NR S4 2 , —C(O)R S4 , —C(O)OR S4 , —C(O)NR S4 2 , —S(O) 2 NR S4 2 , —S(O) 2 R S4 , —OC(O)R S4 , —N(R S4 )C(O)R S4 , —OC(O)OR S4 , —OC(O)NR S4 2 , —N(R S4 )C(O)OR S4 , —N(R S4 )C(O)NR S4 2 , —N(R S4 )S(O) 2 R S4 , —OP(O)(OR S4 ) 2 or —CH 2 —OP(O)(OR S4 ); and

wherein each R S4 is independently hydrogen, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, —(C 0 -C 6 alkyl)-Aryl, —(C 0 -C 6 alkyl)-Heteroaryl, —(C 0 -C 6 alkyl)-Cycloalkyl, or —(C 0 -C 6 alkyl)-Heterocycloalkyl, wherein Aryl, Heteroaryl, Cycloalkyl, Heterocycloalkyl, alkyl, and haloalkyl are optionally substituted with one or two C 1 -C 6 alkyl, halogen, C 1 -C 6 haloalkyl or cyano;

provided that

(a) when ring A is Ar, ring B is not triazolyl or imidazolidin-2-onyl; and

(b) Z is not

2. The compound according to claim 1 having the structure of formula (I),

or a pharmaceutically acceptable salt thereof,

wherein

X is —S— or —N(R′)—;

R′ is hydrogen, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkyloxy, each optionally substituted with 1 to 3 moieties that are each independently C 1 -C 6 alkyl, halogen, C 1 -C 6 haloalkyl or cyano;

R 1 is hydrogen, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkyloxy, —OR S1 , —NR S1 2 , —SR S1 , each optionally substituted with 1 to 3 moieties that are each independently C 1 -C 6 alkyl, halogen, C 1 -C 6 haloalkyl or cyano;

wherein each R S1 is independently hydrogen, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, —(C 0 -C 6 alkyl)-Aryl, —(C 0 -C 6 alkyl)-Heteroalkyl, —(C 0 -C 6 alkyl)-Cycloalkyl, or —(C 0 -C 6 alkyl)-Heterocycloalkyl, wherein Aryl, Heteroaryl, Cycloalkyl, Heterocycloakyl, alkyl, and haloalkyl are optionally substituted with C 1 -C 6 alkyl, halogen, C 1 -C 6 haloalkyl or cyano;

A′ is phenyl optionally substituted with one to five R 2 groups, wherein

each R 2 is independently halogen, —C 1 -C 6 alkyl, —C 1 -C 6 haloalkyl, —C 1 -C 6 alkoxy, —NO 2 or —CN, wherein each alkyl, haloalkyl and alkoxy are optionally substituted with 1, 2, 3, or 4 groups that are each independently halogen, cyano, nitro, —OR S2 , —SR S2 , —NR S2 2 , —C(O)OR S2 , —C(O)NR S2 2 , —C(O)R S2 , —S(O)R S2 , —S(O) 2 R S2 , —S(O)OR S2 , —S(O) 2 OR S2 , —S(O)NR S2 2 , —S(O) 2 NR S2 2 , —OC(O)R S2 , —OC(O)OR S2 , —OC(O)NR S2 2 , —N(R S2 )C(O)R S2 , —N(R S2 )C(O)OR S2 , —N(R S2 )C(O)NR S2 2 , —N(R S2 )S(O)R S2 , —N(R S2 )S(O) 2 R S2 , C 1 -C 6 alkyl, or C 1 -C 6 haloalkyl;

Z is

a fused bicyclic ring of the formula,

wherein

ring A is Ar or 5- or 6-membered Heteroaryl,

ring B is 5- or 6-membered Heteroaryl,

wherein

Z is optionally substituted by one or two —R Z groups that are each independently halogen, cyano, C 1-6 alkyl, C 1-6 haloalkyl, —C 1 -C 6 alkoxy, —OR S3 , —SR S3 , —NR S3 2 , —C(O)R S3 , —C(O)OR S3 , —C(O)NR S3 2 , —S(O) 2 NR S3 2 , —S(O) 2 R S3 , —OC(O)R S3 , —N(R S3 )C(O)R S3 , —OC(O)OR S3 , —OC(O)NR S3 2 , —N(R S3 )C(O)OR S3 , —N(R S3 )C(O)NR S3 2 , —N(R S3 )S(O) 2 R S3 , —OP(O)(OR S3 ) 2 or —CH 2 —OP(O)(OR S3 ), wherein each alkyl, haloalkyl and alkoxy is optionally substituted by one or two —R Z2 groups;

wherein each R S3 is independently hydrogen, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, —(C 0 -C 6 alkyl)-Aryl, —(C 0 -C 6 alkyl)-Heteroaryl, —(C 0 -C 6 alkyl)-Cycloalkyl, or —(C 0 -C 6 alkyl)-Heterocycloalkyl, wherein Aryl, Heteroaryl, Cycloalkyl, Heterocycloalkyl, alkyl, and haloalkyl are optionally substituted with C 1 -C 6 alkyl, halogen, C 1 -C 6 haloalkyl or cyano; and

wherein each R S4 is independently hydrogen, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, —(C 0 -C 6 alkyl)-Aryl, —(C 0 -C 6 alkyl)-Heteroaryl, —(C 0 -C 6 alkyl)-Cycloalkyl, or —(C 0 -C 6 alkyl)-Heterocycloalkyl, wherein Aryl, Heteroaryl, Cycloalkyl, Heterocycloalkyl, alkyl, and haloalkyl are optionally substituted with C 1 -C 6 alkyl, halogen, C 1 -C 6 haloalkyl or cyano;

provided that

(a) when ring A is Ar, ring B is not triazolyl or imidazolidin-2-onyl; and

(b) Z is not

3. The compound of claim 1 , wherein

Z is

(a) a fused bicyclic ring of the formula,

wherein

(1) ring A is —Aryl, and

ring B is a 6-membered Heteroaryl; or

(2) ring A is 6-membered Heteroaryl, and

ring B is a 5-membered Heteroaryl; or

(b)

wherein

z is CH, O, S or N;

y is CH, CH 2 , or N; and

x is CH, O, S, N(R a );

provided that when z is N and x is N(R a ), y is not N;

wherein R a is hydrogen, —C 1 -C 6 alkyl, —C 1 -C 6 haloalkyl, —C(O)OR, —C(O)NR 2 , —C(O)R, —S(O)R, —S(O) 2 R, —S(O)OR, —S(O) 2 OR, —S(O)NR 2 , —S(O) 2 NR 2 , —OC(O)R, —OC(O)OR, —OC(O)NR 2 ;

wherein each R is independently hydrogen, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, —(C 0 -C 6 alkyl)-Aryl, —(C 0 -C 6 alkyl)-Heteroaryl, —(C 0 -C 6 alkyl)-Cycloalkyl, or —(C 0 -C 6 alkyl)-Heterocycloalkyl, wherein Aryl, Heteroaryl, Cycloalkyl, Heterocycloalkyl, alkyl, and haloalkyl are optionally substituted with C 1 -C 6 alkyl, halogen, C 1 -C 6 haloalkyl or cyano;

wherein Z is optionally substituted by one or two —R Z groups.

4. A compound according to claim 1 that is,

5-(4-Phenyl-1H-imidazol-5-yl)-1H-indazole;

6-(4-Phenyl-1H-imidazol-5-yl)-1H-indazole;

5-(4-(4-Fluoro-3-methylphenyl)-1H-imidazol-5-yl)-1H-indazole;

6-(4-(4-Fluoro-3-methylphenyl)-1H-imidazol-5-yl)-1H-indazole;

6-(4-(4-Fluoro-3-methylphenyl)-1-methyl-1H-imidazol-5-yl)-1H-indazole;

5-(4-(4-Chlorophenyl)-1H-imidazol-5-yl)-1H-indazole;

6-(4-(4-Fluoro-3-methylphenyl)-1-methyl-1H-imidazol-5-yl)-1H-indazole;

6-(4-(4-Fluoro-3-methylphenyl)-1-methyl-1H-imidazol-5-yl)-1-methyl-1H-benzo[d]imidazole;

6-(4-(4-Fluoro-3-methylphenyl)-1-methyl-1H-imidazol-5-yl)benzo[d]thiazole;

5-(4-(4-Fluorophenyl)-1H-imidazol-5-yl)-1H-indazole;

6-(4-(4-Fluorophenyl)-1H-imidazol-5-yl)-1H-indazole;

6-(4-(4-Fluorophenyl)-1H-imidazol-5-yl)-1-methyl-1H-benzo[d]imidazole;

6-(4-(4-Fluorophenyl)-1H-imidazol-5-yl)benzo[d]thiazole;

6-(4-(4-Fluorophenyl)-1H-imidazol-5-yl)imidazo[1,2-a]pyridine;

5-(4-(m-Tolyl)-1H-imidazol-5-yl)-1H-indazole;

6-(4-(m-Tolyl)-1H-imidazol-5-yl)-1H-indazole;

1-Methyl-6-(4-(m-tolyl)-1H-imidazol-5-yl)-1H-benzo[d]imidazole;

6-(4-(m-Tolyl)-1H-imidazol-5-yl)benzo[d]thiazole;

6-(4-(m-Tolyl)-1H-imidazol-5-yl)imidazo[1,2-a]pyridine;

6-(4-(m-Tolyl)-1H-imidazol-5-yl)quinoxaline;

6-(4-(4-Fluoro-3-methylphenyl)-1-methyl-1H-imidazol-5-yl)quinoxaline;

5-(4-(3-Chlorophenyl)-1H-imidazol-5-yl)-1H-indazole;

6-(4-(3-Chlorophenyl)-1H-imidazol-5-yl)-1H-indazole;

6-(4-(3-Chlorophenyl)-1H-imidazol-5-yl)-1-methyl-1H-benzo[d]imidazole;

6-(4-(3-Chlorophenyl)-1H-imidazol-5-yl)benzo[d]thiazole;

6-(4-(3-Chlorophenyl)-1H-imidazol-5-yl)imidazo[1,2-a]pyridine;

5-(4-(3-Fluorophenyl)-1H-imidazol-5-yl)-1H-indazole;

6-(4-(3-Fluorophenyl)-1H-imidazol-5-yl)-1H-indazole;

6-(4-(3-Fluorophenyl)-1H-imidazol-5-yl)-1-methyl-1H-benzo[d]imidazole;

6-(4-(3-Fluorophenyl)-1H-imidazol-5-yl)benzo[d]thiazole;

5-(4-(3,4-Difluorophenyl)-1H-imidazol-5-yl)-1H-indazole;

6-(4-(3,4-Difluorophenyl)-1H-imidazol-5-yl)-1H-indazole;

6-(4-(3,4-Difluorophenyl)-1H-imidazol-5-yl)-1-methyl-1H-benzo[d]imidazole;

6-(4-(3,4-Difluorophenyl)-1H-imidazol-5-yl)benzo[d]thiazole;

6-(4-(3,4-Difluorophenyl)-1H-imidazol-5-yl)imidazo[1,2-a]pyridine;

6-(4-(3,4-Difluorophenyl)-1H-imidazol-5-yl)quinoline;

6-(4-(4-Fluoro-3-methylphenyl)-1-methyl-1H-imidazol-5-yl)quinoline;

6-(4-(4-Fluorophenyl)-1H-imidazol-5-yl)quinoline;

6-(4-(3-Chlorophenyl)-1H-imidazol-5-yl)quinoline;

6-(4-(3-Fluorophenyl)-1H-imidazol-5-yl)quinolone;

5-(1-Methyl-4-(m-tolyl)-1H-imidazol-5-yl)-1H-indazole;

6-(1-Methyl-4-(m-tolyl)-1H-imidazol-5-yl)-1H-indazole;

1-Methyl-6-(1-methyl-4-(m-tolyl)-1H-imidazol-5-yl)-1H-benzo[d]imidazole;

6-(1-Methyl-4-(m-tolyl)-1H-imidazol-5-yl)benzo[d]thiazole;

6-(1-Methyl-4-(m-tolyl)-1H-imidazol-5-yl)imidazo[1,2-a]pyridine;

6-(1-Methyl-4-(m-tolyl)-1H-imidazol-5-yl)quinoline;

6-(1-Methyl-4-(m-tolyl)-1H-imidazol-5-yl)quinoxaline;

5-(4-(4-Fluorophenyl)-1-methyl-1H-imidazol-5-yl)-1H-indazole;

6-(4-(4-Fluorophenyl)-1-methyl-1H-imidazol-5-yl)-1H-indazole;

6-(4-(4-Fluorophenyl)-1-methyl-1H-imidazol-5-yl)-1-methyl-1H-benzo[d]imidazole;

6-(4-(4-Fluorophenyl)-1-methyl-1H-imidazol-5-yl)benzo[d]thiazole;

5-(4-(4-Fluoro-3-methylphenyl)-1,2-dimethyl-1H-imidazol-5-yl)-1H-indazole;

6-(4-(4-Fluoro-3-methylphenyl)-1,2-dimethyl-1H-imidazol-5-yl)-1H-indazole;

6-(4-(4-Fluoro-3-methylphenyl)-1,2-dimethyl-1H-imidazol-5-yl)-1-methyl-1H-benzo[d]imidazole;

6-(4-(4-Fluoro-3-methylphenyl)-1,2-dimethyl-1H-imidazol-5-yl)benzo[d]thiazole;

5-(1,2-Dimethyl-4-(m-tolyl)-1H-imidazol-5-yl)-1H-indazole;

6-(1,2-Dimethyl-4-(m-tolyl)-1H-imidazol-5-yl)-1H-indazole;

6-(1,2-Dimethyl-4-(m-tolyl)-1H-imidazol-5-yl)-1-methyl-1H-benzo[d]imidazole;

6-(1,2-Dimethyl-4-(m-tolyl)-1H-imidazol-5-yl)benzo[d]thiazole;

5-(4-(3-Chlorophenyl)-1-methyl-1H-imidazol-5-yl)-1H-indazole;

6-(4-(3-Chlorophenyl)-1-methyl-1H-imidazol-5-yl)-1H-indazole;

6-(4-(3-Chlorophenyl)-1-methyl-1H-imidazol-5-yl)-1-methyl-1H-benzo[d]imidazole;

6-(4-(3-Chlorophenyl)-1-methyl-1H-imidazol-5-yl)benzo[d]thiazole;

5-(4-(3,4-Difluorophenyl)-1-methyl-1H-imidazol-5-yl)-1H-indazole;

6-(4-(3,4-Difluorophenyl)-1-methyl-1H-imidazol-5-yl)-1H-indazole;

6-(4-(3,4-Difluorophenyl)-1-methyl-1H-imidazol-5-yl)-1-methyl-1H-benzo[d]imidazole;

6-(4-(3,4-Difluorophenyl)-1-methyl-1H-imidazol-5-yl)benzo[d]thiazole;

6-(4-(3,4-Difluorophenyl)-1-methyl-1H-imidazol-5-yl)quinoxaline;

5-(4-(4-Methoxyphenyl)-1-methyl-1H-imidazol-5-yl)-1H-indazole;

6-(4-(4-Methoxyphenyl)-1-methyl-1H-imidazol-5-yl)-1H-indazole;

5-(4-(4-Fluoro-3-methylphenyl)-2-methyl-1H-imidazol-5-yl)-1H-indazole;

6-(4-(4-Fluoro-3-methylphenyl)-2-methyl-1H-imidazol-5-yl)-1H-indazole;

6-(4-(4-Fluoro-3-methylphenyl)-2-methyl-1H-imidazol-5-yl)benzo[d]thiazole;

6-(4-(4-Fluoro-3-methylphenyl)-2-methyl-1H-imidazol-5-yl)imidazo[1,2-a]pyridine;

6-(4-(4-Fluoro-3-methylphenyl)-2-methyl-1H-imidazol-5-yl)quinoline;

6-(4-(4-Fluoro-3-methylphenyl)-2-methyl-1H-imidazol-5-yl)quinoxaline;

5-(4-(4-Fluorophenyl)-2-methyl-1H-imidazol-5-yl)-1H-indazole;

6-(4-(4-Fluorophenyl)-2-methyl-1H-imidazol-5-yl)-1H-indazole;

6-(4-(4-Fluorophenyl)-2-methyl-1H-imidazol-5-yl)-1-methyl-1H-benzo[d]imidazole;

6-(4-(4-Fluorophenyl)-2-methyl-1H-imidazol-5-yl)benzo[d]thiazole;

6-(4-(4-Fluorophenyl)-2-methyl-1H-imidazol-5-yl)imidazo[1,2-a]pyridine;

6-(4-(4-Fluorophenyl)-2-methyl-1H-imidazol-5-yl)quinoxaline;

5-(4-(3,4-Difluorophenyl)-2-methyl-1H-imidazol-5-yl)-1H-indazole;

6-(4-(3,4-Difluorophenyl)-2-methyl-1H-imidazol-5-yl)-1H-indazole;

6-(4-(3,4-Difluorophenyl)-2-methyl-1H-imidazol-5-yl)-1-methyl-1H-benzo[d]imidazole;

6-(4-(3,4-Difluorophenyl)-2-methyl-1H-imidazol-5-yl)benzo[d]thiazole;

6-(4-(3,4-Difluorophenyl)-2-methyl-1H-imidazol-5-yl)imidazo[1,2-a]pyridine;

6-(4-(3,4-Difluorophenyl)-2-methyl-1H-imidazol-5-yl)quinoline;

6-(4-(3,4-Difluorophenyl)-2-methyl-1H-imidazol-5-yl)quinoxaline;

5-(2-Methyl-4-(3,4,5-trifluorophenyl)-1H-imidazol-5-yl)-1H-indazole;

6-(2-Methyl-4-(3,4, 5-trifluorophenyl)-1H-imidazol-5-yl)-1H-indazole;

6-(2-Methyl-4-(3,4,5-trifluorophenyl)-1H-imidazol-5-yl)-[1,2,4]triazolo[1,5-a]pyridine;

6-(2-Methyl-4-(3,4,5-trifluorophenyl)-1H-imidazol-5-yl)benzo[d]thiazole;

6-(2-Methyl-4-(3,4,5-trifluorophenyl)-1H-imidazol-5-yl)imidazo[1,2-a]pyridine;

6-(2-Methyl-4-(3,4,5-trifluorophenyl)-1H-imidazol-5-yl)quinoline;

6-(2-Methyl-4-(3,4, 5-trifluorophenyl)-1H-imidazol-5-yl)quinoxaline;

5-(2-Methyl-4-(2,4,5-trifluorophenyl)-1H-imidazol-5-yl)-1H-indazole;

6-(2-Methyl-4-(2,4,5-trifluorophenyl)-1H-imidazol-5-yl)-[1,2,4]triazolo[1,5-a]pyridine;

6-(2-Methyl-4-(2,4,5-trifluorophenyl)-1H-imidazol-5-yl)benzo[d]thiazole;

6-(2-Methyl-4-(2,4,5-trifluorophenyl)-1H-imidazol-5-yl)quinoline;

5-(4-(3-Chlorophenyl)-2-methyl-1H-imidazol-5-yl)-1H-indazole;

6-(4-(3-Chlorophenyl)-2-methyl-1H-imidazol-5-yl)-1H-indazole;

6-(4-(3-Chlorophenyl)-2-methyl-1H-imidazol-5-yl)-[1,2,4]triazolo[1,5-a]pyridine;

6-(4-(3-Chlorophenyl)-2-methyl-1H-imidazol-5-yl)imidazo[1,2-a]pyridine;

6-(4-(3-Chlorophenyl)-2-methyl-1H-imidazol-5-yl)quinoline;

5-(2-Ethyl-4-(4-fluoro-3-methylphenyl)-1H-imidazol-5-yl)-1H-indazole;

6-(2-Ethyl-4-(4-fluoro-3-methylphenyl)-1H-imidazol-5-yl)-1H-indazole;

6-(2-Ethyl-4-(4-fluoro-3-methylphenyl)-1H-imidazol-5-yl)-[1,2,4]triazolo[1, 5-a]pyridine;

6-(2-Ethyl-4-(4-fluoro-3-methylphenyl)-1H-imidazol-5-yl)benzo[d]thiazole;

6-(2-Ethyl-4-(4-fluoro-3-methylphenyl)-1H-imidazol-5-yl)imidazo[1,2-a]pyridine;

6-(2-Ethyl-4-(4-fluoro-3-methylphenyl)-1H-imidazol-5-yl)quinoline;

6-(2-Ethyl-4-(4-fluoro-3-methylphenyl)-1H-imidazol-5-yl)quinoxaline;

5-(2-Ethyl-4-(m-tolyl)-1H-imidazol-5-yl)-1H-indazole;

6-(2-Ethyl-4-(m-tolyl)-1H-imidazol-5-yl)-1H-indazole;

6-(2-Ethyl-4-(m-tolyl)-1H-imidazol-5-yl)-[1,2,4]triazolo[1,5-a]pyridine;

6-(2-Ethyl-4-(m-tolyl)-1H-imidazol-5-yl)benzo[d]thiazole;

6-(2-Ethyl-4-(m-tolyl)-1H-imidazol-5-yl)imidazo[1,2-a]pyridine;

6-(2-Ethyl-4-(m-tolyl)-1H-imidazol-5-yl)quinoxaline;

5-(2-Ethyl-4-(4-fluorophenyl)-1H-imidazol-5-yl)-1H-indazole;

6-(2-Ethyl-4-(4-fluorophenyl)-1H-imidazol-5-yl)-1H-indazole;

6-(2-Ethyl-4-(4-fluorophenyl)-1H-imidazol-5-yl)-[1,2,4]triazolo[1,5-a]pyridine;

6-(2-Ethyl-4-(4-fluorophenyl)-1H-imidazol-5-yl)benzo[d]thiazole;

6-(2-Ethyl-4-(4-fluorophenyl)-1H-imidazol-5-yl)imidazo[1,2-a]pyridine;

5-(4-(3-Chlorophenyl)-2-ethyl-1H-imidazol-5-yl)-1H-indazole;

6-(4-(3-Chlorophenyl)-2-ethyl-1H-imidazol-5-yl)-[1,2,4]triazolo[1,5-a]pyridine;

6-(4-(3-Chlorophenyl)-2-ethyl-1H-imidazol-5-yl)benzo[d]thiazole;

6-(4-(3-Chlorophenyl)-2-ethyl-1H-imidazol-5-yl)imidazo[1,2-a]pyridine;

6-(4-(3-Chlorophenyl)-2-ethyl-1H-imidazol-5-yl)quinoline;

6-(4-(3-Chlorophenyl)-2-ethyl-1H-imidazol-5-yl)quinoxaline;

5-(4-(3,4-Difluorophenyl)-2-ethyl-1H-imidazol-5-yl)-1H-indazole;

6-(4-(3,4-Difluorophenyl)-2-ethyl-1H-imidazol-5-yl)-1H-indazole;

6-(4-(3,4-Difluorophenyl)-2-ethyl-1H-imidazol-5-yl)-[1,2,4]triazolo[1,5-a]pyridine;

6-(4-(3,4-Difluorophenyl)-2-ethyl-1H-imidazol-5-yl)benzo[d]thiazole;

6-(4-(3,4-Difluorophenyl)-2-ethyl-1H-imidazol-5-yl)imidazo[1,2-a]pyridine;

6-(4-(3,4-Difluorophenyl)-2-ethyl-1H-imidazol-5-yl)quinoxaline;

6-(2-Ethyl-4-(3-fluorophenyl)-1H-imidazol-5-yl)-[1,2,4]triazolo[1,5-a]pyridine;

6-(2-Ethyl-4-(3-fluorophenyl)-1H-imidazol-5-yl)benzo[d]thiazole;

6-(2-Ethyl-4-(3-fluorophenyl)-1H-imidazol-5-yl)imidazo[1,2-a]pyridine;

5-(4-(3-Chloro-5-fluorophenyl)-2-ethyl-1H-imidazol-5-yl)-1H-indazole;

6-(4-(3-Chloro-5-fluorophenyl)-2-ethyl-1H-imidazol-5-yl)benzo[d]thiazole;

6-(4-(3-Chloro-5-fluorophenyl)-2-ethyl-1H-imidazol-5-yl)quinoxaline;

5-(2-Ethyl-4-(3-fluoro-5-methylphenyl)-1H-imidazol-5-yl)-1H-indazole;

6-(2-Ethyl-4-(3-fluoro-5-methylphenyl)-1H-imidazol-5-yl)-1H-indazole;

6-(2-Ethyl-4-(3-fluoro-5-methylphenyl)-1H-imidazol-5-yl)-[1,2,4]triazolo[1,5-a]pyridine;

6-(2-Ethyl-4-(3-fluoro-5-methylphenyl)-1H-imidazol-5-yl)benzo[d]thiazole;

6-(2-Ethyl-4-(3-fluoro-5-methylphenyl)-1H-imidazol-5-yl)imidazo[1,2-a]pyridine;

6-(2-Ethyl-4-(3-fluoro-5-methylphenyl)-1H-imidazol-5-yl)quinoxaline;

5-(4-(3,5-Difluorophenyl)-2-methyl-1H-imidazol-5-yl)-1H-indazole;

6-(4-(3,5-Difluorophenyl)-2-ethyl-1H-imidazol-5-yl)benzo[d]thiazole;

6-(4-(3-Chlorophenyl)-2-(trifluoromethyl)-1H-imidazol-5-yl)-[1,2,4]triazolo[1,5-a]pyridine;

6-(4-(4-Fluorophenyl)-2-(trifluoromethyl)-1H-imidazol-5-yl)-[1,2,4]triazolo[1,5-a]pyridine;

6-(2-Isopropyl-4-(m-tolyl)-1H-imidazol-5-yl)-[1,2,4]triazolo[1,5-a]pyridine;

5-(1H-indazol-6-yl)-4-(m-tolyl)thiazole;

5-(1H-indazol-5-yl)-4-(m-tolyl)thiazole;

4-(4-fluoro-3-methylphenyl)-5-(imidazo[1,2-a]pyridin-6-yl)thiazol-2-amine;

4-(4-fluoro-3-methylphenyl)-5-(1H-indazol-5-yl)thiazole;

5-(1H-indazol-5-yl)-4-(4-methoxyphenyl)thiazol-2-amine;

4-(4-fluoro-3-methylphenyl)-5-(quinoxalin-6-yl)thiazol-2-amine;

4-(4-fluoro-3-methylphenyl)-5-(1H-indazol-6-yl)thiazole;

4-(4-fluoro-3-methylphenyl)-5-(1H-indazol-5-yl)thiazol-2-amine;

6-(4-(m-tolyl)thiazol-5-yl)benzo[d]thiazole;

5-(benzo[d]thiazol-6-yl)-4-(4-fluoro-3-methylphenyl)thiazol-2-amine;

5-(imidazo[1,2-a]pyridin-6-yl)-4-(4-methoxyphenyl)thiazol-2-amine;

4-(3-chlorophenyl)-5-(imidazo[1,2-a]pyridin-6-yl)thiazol-2-amine;

6-(4-(4-fluoro-3-methylphenyl)thiazol-5-yl)benzo[d]thiazole;

6-(4-(3-chlorophenyl)thiazol-5-yl)benzo[d]thiazole;

4-(4-fluoro-3-methylphenyl)-5-(imidazo[1,2-a]pyridin-6-yl)thiazole;

4-(3-chlorophenyl)-5-(1H-indazol-5-yl)thiazol-2-amine;

4-(3-chlorophenyl)-5-(quinoxalin-6-yl)thiazol-2-amine;

4-(4-fluorophenyl)-5-(quinoxalin-6-yl)thiazol-2-amine;

5-(imidazo[1,2-a]pyridin-6-yl)-4-(3-(trifluoromethyl)phenyl)thiazol-2-amine;

4-(3-chlorophenyl)-5-(1H-indazol-6-yl)thiazol-2-amine;

5-(1H-indazol-6-yl)-4-(4-methoxyphenyl)thiazol-2-amine;

4-(4-fluoro-3-methylphenyl)-5-(1H-indazol-6-yl)thiazol-2-amine;

5-(1H-indazol-5-yl)-4-(3-(trifluoromethyl)phenyl)thiazol-2-amine;

5-(benzo[d]thiazol-6-yl)-4-(3-(trifluoromethyl)phenyl)thiazol-2-amine;

5-(1H-indazol-5-yl)-4-(3-methoxyphenyl)thiazol-2-amine;

5-(benzo[d]thiazol-6-yl)-4-(3-fluorophenyl)thiazol-2-amine;

4-(3-fluorophenyl)-5-(1H-indazol-5-yl)thiazol-2-amine;

5-(quinoxalin-6-yl)-4-(3-(trifluoromethyl)phenyl)thiazol-2-amine;

6-(4-(4-fluorophenyl)thiazol-5-yl)benzo[d]thiazole;

4-(4-methoxyphenyl)-5-(quinoxalin-6-yl)thiazol-2-amine;

4-(3-fluorophenyl)-5-(quinoxalin-6-yl)thiazol-2-amine;

5-(imidazo[1,2-a]pyridin-6-yl)-4-(3-methoxyphenyl)thiazol-2-amine;

5-(1H-indazol-6-yl)-4-(3-(trifluoromethyl)phenyl)thiazol-2-amine;

5-(benzo[d]thiazol-6-yl)-4-(3-methoxyphenyl)thiazol-2-amine;

4-(3-fluorophenyl)-5-(imidazo[1,2-a]pyridin-6-yl)thiazol-2-amine;

4-(4-fluorophenyl)-5-(imidazo[1,2-a]pyridin-6-yl)-N-methylthiazol-2-amine;

or a pharmaceutically acceptable salt thereof.

5. The compound according to claim 1 having the structure of formula (II),

or a pharmaceutically acceptable salt thereof,

wherein

R′ is hydrogen or C 1 -C 6 alkyl;

R 1 is hydrogen or C 1 -C 6 alkyl;

each R 2 is independently hydrogen, halogen or —C 1 -C 6 alkyl;

Z is

(a) a fused bicyclic ring of the formula,

wherein

ring A is 6-membered Heteroaryl, and

ring B is a 5-membered Heteroaryl; or

(b)

wherein

z is CH, O, S or N;

y is CH, CH 2 , or N; and

x is CH, O, S, N(R a );

provided that when z is N and x is N(R a ), y is not N;

wherein R a is hydrogen or —C 1 -C 6 alkyl.

6. The compound of claim 5 , wherein

Z is

7. The compound of claim 5 , wherein the compound is,

5-(4-Phenyl-1H-imidazol-5-yl)-1H-indazole;

6-(4-Phenyl-1H-imidazol-5-yl)-1H-indazole;

5-(4-(4-Fluoro-3-methylphenyl)-1H-imidazol-5-yl)-1H-indazole;

6-(4-(4-Fluoro-3-methylphenyl)-1H-imidazol-5-yl)-1H-indazole;

6-(4-(4-Fluoro-3-methylphenyl)-1-methyl-1H-imidazol-5-yl)-1H-indazole;

5-(4-(4-Chlorophenyl)-1H-imidazol-5-yl)-1H-indazole;

6-(4-(4-Fluoro-3-methylphenyl)-1-methyl-1H-imidazol-5-yl)-1H-indazole;

6-(4-(4-Fluoro-3-methylphenyl)-1-methyl-1H-imidazol-5-yl)-1-methyl-1H-benzo[d]imidazole;

6-(4-(4-Fluoro-3-methylphenyl)-1-methyl-1H-imidazol-5-yl)benzo[d]thiazole;

5-(4-(4-Fluorophenyl)-1H-imidazol-5-yl)-1H-indazole;

6-(4-(4-Fluorophenyl)-1H-imidazol-5-yl)-1H-indazole;

5-(4-(m-Tolyl)-1H-imidazol-5-yl)-1H-indazole;

6-(4-(m-Tolyl)-1H-imidazol-5-yl)-1H-indazole;

1-Methyl-6-(4-(m-tolyl)-1H-imidazol-5-yl)-1H-benzo[d]imidazole;

6-(4-(m-Tolyl)-1H-imidazol-5-yl)benzo[d]thiazole;

5-(4-(3-Chlorophenyl)-1H-imidazol-5-yl)-1H-indazole;

6-(4-(3-Chlorophenyl)-1H-imidazol-5-yl)-1H-indazole;

6-(4-(3-Chlorophenyl)-1H-imidazol-5-yl)-1-methyl-1H-benzo[d]imidazole;

6-(4-(3-Chlorophenyl)-1H-imidazol-5-yl)benzo[d]thiazole;

5-(4-(3-Fluorophenyl)-1H-imidazol-5-yl)-1H-indazole;

6-(4-(3-Fluorophenyl)-1H-imidazol-5-yl)-1H-indazole;

5-(4-(3,4-Difluorophenyl)-1H-imidazol-5-yl)-1H-indazole;

6-(4-(3,4-Difluorophenyl)-1H-imidazol-5-yl)-1H-indazole;

6-(4-(3,4-Difluorophenyl)-1H-imidazol-5-yl)-1-methyl-1H-benzo[d]imidazole;

6-(4-(3,4-Difluorophenyl)-1H-imidazol-5-yl)benzo[d]thiazole;

5-(1-Methyl-4-(m-tolyl)-1H-imidazol-5-yl)-1H-indazole;

6-(1-Methyl-4-(m-tolyl)-1H-imidazol-5-yl)-1H-indazole;

5-(4-(4-Fluorophenyl)-1-methyl-1H-imidazol-5-yl)-1H-indazole;

5-(4-(3-Chlorophenyl)-1-methyl-1H-imidazol-5-yl)-1H-indazole;

6-(4-(3-Chlorophenyl)-1-methyl-1H-imidazol-5-yl)-1H-indazole;

6-(4-(3-Chlorophenyl)-1-methyl-1H-imidazol-5-yl)-1b-methyl-1H-benzo[d]imidazole;

6-(4-(3-Chlorophenyl)-1-methyl-1H-imidazol-5-yl)benzo[d]thiazole;

5-(4-(3,4-Difluorophenyl)-1)-2-methyl-1H-imidazol-5-yl)-1H-indazole;

5-(4-(4-Fluoro-3-methylphenyl)-2-methyl-1H-imidazol-5-yl)-1H-indazole;

6-(2-Methyl-4-(2,4,5-trifluorophenyl)-1H-imidazol-5-yl)-[benzo 1,2,4]triazoloe[1,5-a]pyridine;

6-(2-Methyl-4-(2,4,5-trifluorophenyl)-1H-imidazol-5-yl)benzo[d]thiazole;

6-(4-(3-Chlorophenyl)-2-methyl-1H-imidazol-5-yl)-1H-indazole;

6-(4-(3-Chlorophenyl)-2-methyl-1H-imidazol-5-yl)imidazo[1,2-a]pyridine;

6-(2-Ethyl-4-(4-fluoro-3-methylphenyl)-1H-imidazol-5-yl)-[1,2,4]triazolo[1,5-a]pyridine;

6-(4-(3-Chlorophenyl)-2-ethyl-1H-imidazol-5-yl)-[1,2,4]triazolo[1,5-a]pyridine;

6-(4-(3-Chlorophenyl)-2-ethyl-1H-imidazol-5-yl)benzo[d]thiazole;

or a pharmaceutically acceptable salt thereof.

8. The compound according to claim 1 having the structure of formula (III),

or a pharmaceutically acceptable salt thereof,

wherein

R′ is hydrogen or C 1 -C 6 alkyl;

each R 2 is independently hydrogen, halogen or —C 1 -C 6 alkyl;

z is CH, O, S or N;

y is CH, CH 2 , or N; and

x is CH, O, S, N(R a );

wherein R a is hydrogen or —C 1 -C 6 alkyl;

provided that when z is N and x is N(R a ), y is not N.

9. The compound of claim 8 , wherein

Z is

wherein each R a is independently hydrogen or —C 1 -C 6 alkyl.

10. The compound of claim 7 , wherein the compound is,

5-(4-(4-Fluoro-3-methylphenyl)-1H-imidazol-5-yl)-1H-indazole;

6-(4-(4-Fluoro-3-methylphenyl)-1H-imidazol-5-yl)-1H-indazole;

6-(4-(4-Fluoro-3-methylphenyl)-1-methyl-1H-imidazol-5-yl)-1H-indazole;

5-(4-(4-Fluorophenyl)-1H-imidazol-5-yl)-1H-indazole;

6-(4-(4-Fluorophenyl)-1H-imidazol-5-yl)-1H-indazole;

5-(4-(m-Tolyl)-1H-imidazol-5-yl)-1H-indazole;

6-(4-(m-Tolyl)-1H-imidazol-5-yl)-1H-indazole;

6-(4-(m-Tolyl)-1H-imidazol-5-yl)benzo[d]thiazole;

5-(4-(3-Chlorophenyl)-1H-imidazol-5-yl)-1H-indazole;

6-(4-(3-Chlorophenyl)-1H-imidazol-5-yl)-1H-indazole;

6-(4-(3-Chlorophenyl)-1H-imidazol-5-yl)-1-methyl-1H-benzo[d]imidazole;

6-(4-(3-Chlorophenyl)-1H-imidazol-5-yl)benzo[d]thiazole;

5-(4-(3-Fluorophenyl)-1H-imidazol-5-yl)-1H-indazole;

6-(4-(3-Fluorophenyl)-1H-imidazol-5-yl)-1H-indazole;

5-(4-(3,4-Difluorophenyl)-1H-imidazol-5-yl)-1H-indazole;

5-(1-Methyl-4-(m-tolyl)-1H-imidazol-5-yl)-1H-indazole;

6-(1-Methyl-4-(m-tolyl)-1H-imidazol-5-yl)-1H-indazole;

5-(4-(3-Chlorophenyl)-1-methyl-1H-imidazol-5-yl)-1H-indazole;

6-(4-(3-Chlorophenyl)-1-methyl-1H-imidazol-5-yl)-1H-indazole;

or a pharmaceutically acceptable salt thereof.

11. A pharmaceutical composition comprising a pharmaceutically acceptable diluent, carrier, or excipient and a compound according to claim 1 .

12. A compound according to claim 1 that is:

6-(1-(2,2-difluoroethyl)-4-(4-fluorophenyl)-1H-imidazol-5-yl)imidazo[1,2-b]pyridazine-3-carbonitrile

6-(4-(4-fluorophenyl)-1-cis-3-hydroxycyclobutyl)-1H-imidazol-5-yl)imidazo[1,2-b]pyridazine-3-carbonitrile

6-(1-(3,3-difluorocyclobutyl)-4-(4-fluorophenyl)-1H-imidazol-5-yl)imidazo[1,2-b]pyridazine-3-carbonitrile

6-(4-(4-fluorophenyl)-1-(3,3,3-trifluoropropyl)-1H-imidazol-5-yl)imidazo[1,2-b]pyridazine-3-carbonitrile

6-(1-(3,3-difluorocyclopentyl)-4-(4-fluorophenyl)-1H-imidazol-5-yl)imidazo[1,2-b]pyridazine-3-carbonitrile

(S)-6-(4-(4-fluorophenyl)-1-(1-hydroxybutan-2-yl)-1H-imidazol-5-yl)imidazo[1,2-b]pyridazine-3-carbonitrile

6-(1-cyclopropyl-4-(4-fluorophenyl)-1H-imidazol-5-yl)imidazo[1,2-b]pyridazine-3-carbonitrile

6-(1-(4,4-difluorocyclohexyl)-4-(4-fluorophenyl)-1H-imidazol-5-yl)imidazo[1,2-b]pyridazine-3-carbonitrile

6-(1-(2-fluoroethyl)-4-(4-fluorophenyl)-1H-imidazol-5-yl)imidazo[1,2-b]pyridazine-3-carbonitrile

6-(1-ethyl-4-(4-fluorophenyl)-1H-imidazol-5-yl)imidazo[1,2-b]pyridazine-3-carbonitrile

6-(4-(4-fluorophenyl)-1-(2-isopropoxyethyl)-1H-imidazol-5-yl)imidazo[1,2-b]pyridazine-3-carbonitrile

6-(4-(4-fluorophenyl)-1-(3-hydroxy-3-methylbutyl)-1H-imidazol-5-yl)imidazo[1,2-b]pyridazine-3-carbonitrile

6-(4-(4-fluorophenyl)-1-(oxetan-3-yl)-1H-imidazol-5-yl)imidazo[1,2-b]pyridazine-3-carbonitrile

6-(4-(4-fluorophenyl)-1-(2-hydroxyethyl)-1H-imidazol-5-yl)imidazo[1,2-b]pyridazine-3-carbonitrile

6-(4-(4-fluorophenyl)-1-(3-hydroxypropyl)-1H-imidazol-5-yl)imidazo[1,2-b]pyridazine-3-carbonitrile

6-(1-(1-cyclopropyl-2-methoxyethyl)-4-(4-fluorophenyl)-H-imidazol-5-yl)imidazo[1,2-b]pyridazine-3-carbonitrile

6-(4-(4-fluorophenyl)-1-(2-hydroxycyclohexyl)-1H-imidazol-5-yl)imidazo[1,2-b]pyridazine-3-carbonitrile

6-(4-(4-fluorophenyl)-1H-imidazol-5-yl)imidazo[1,2-b]pyridazine-3-carbonitrile 6-(4-(4-fluorophenyl)-1-methyl-1H-imidazol-5-yl)imidazo[1,2-b]pyridazine-3-carbonitrile

6-(1-(3,3-difluoropropyl)-4-(4-fluorophenyl)-1H-imidazol-5-yl)imidazo[1,2-b]pyridazine-3-carbonitrile

6-(4-(4-fluorophenyl)-1-(3-fluoropropyl)-1H-imidazol-5-yl)imidazo[1,2-b]pyridazine-3-carbonitrile

6-(1-(2,2-difluoropropyl)-4-(4-fluorophenyl)-1H-imidazol-5-yl)imidazo[1,2-b]pyridazine-3-carbonitrile

6-(1-(2-fluoro-2-methylpropyl)-4-(4-fluorophenyl)-1H-imidazol-5-yl)imidazo[1,2-b]pyridazine-3-carbonitrile

6-(4-(4-fluorophenyl)-1-isopropyl-1H-imidazol-5-yl)imidazo[1,2-b]pyridazine-3-carbonitrile

6-(1-(bicyclo[1.1.1]pentan-1-yl)-4-(4-fluorophenyl)-1H-imidazol-5-yl)imidazo[1,2-b]pyridazine-3-carbonitrile

6-(4-(4-fluorophenyl)-1-(2-hydroxy-2-methylpropyl)-1H-imidazol-5-yl)imidazo[1,2-b]pyridazine-3-carbonitrile

6-(4-(4-fluorophenyl)-1-(3-(hydroxymethyl)cyclobutyl)-1H-imidazol-5-yl)imidazo[1,2-b]pyridazine-3-carbonitrile

(R)-6-(4-(4-fluorophenyl)-1-(4,4,4-trifluoro-1-hydroxybutan-2-yl)-1H-imidazol-5-yl)imidazo[1,2-b]pyridazine-3-carbonitrile

(S)-6-(4-(4-fluorophenyl)-1-(4,4,4-trifluoro-1-hydroxybutan-2-yl)-1H-imidazol-5-yl)imidazo[1,2-b]pyridazine-3-carbonitrile

6-(4-(4-fluorophenyl)-1-(tert-pentyl)-1H-imidazol-5-yl)imidazo[1,2-b]pyridazine-3-carbonitrile

6-(4-(4-fluorophenyl)-1-((tetrahydrofuran-2-yl)methyl)-1H-imidazol-5-yl)imidazo[1,2-b]pyridazine-3-carbonitrile

6-(4-(3-chloro-4-fluorophenyl)-1-(2-hydroxyethyl)-1H-imidazol-5-yl)imidazo[1,2-b]pyridazine-3-carbonitrile

6-(4-(3-chloro-4-fluorophenyl)-1-(2,2-difluoroethyl)-1H-imidazol-5-yl)imidazo[1,2-b]pyridazine-3-carbonitrile

6-(4-(3-chloro-4-fluorophenyl)-1-(2-fluoroethyl)-1H-imidazol-5-yl)imidazo[1,2-b]pyridazine-3-carbonitrile

6-(4-(3-chloro-4-fluorophenyl)-1-(3,3,3-trifluoropropyl)-1H-imidazol-5-yl)imidazo[1,2-b]pyridazine-3-carbonitrile

6-(4-(3-chloro-4-fluorophenyl)-1-cyclopropyl-1H-imidazol-5-yl)imidazo[1,2-b]pyridazine-3-carbonitrile

6-(4-(3-chloro-4-fluorophenyl)-1-(3-hydroxy-3-methylbutyl)-1H-imidazol-5-yl)imidazo[1,2-b]pyridazine-3-carbonitrile

6-(4-(3-chloro-4-fluorophenyl)-1-(3-hydroxypropyl)-1H-imidazol-5-yl)imidazo[1,2-b]pyridazine-3-carbonitrile

6-(4-(3-chloro-4-fluorophenyl)-1-((cis)-3-hydroxycyclobutyl)-1H-imidazol-5-yl)imidazo[1,2-b]pyridazine-3-carbonitrile

6-(4-(3-chloro-4-fluorophenyl)-1-(2-cyclobutylethyl)-1H-imidazol-5-yl)imidazo[1,2-b]pyridazine-3-carbonitrile

6-(4-(3-chloro-4-fluorophenyl)-1-(1-methylcyclopropyl)-1H-imidazol-5-yl)imidazo[1,2-b]pyridazine-3-carbonitrile

(S)-6-(4-(3-chloro-4-fluorophenyl)-1-((tetrahydrofuran-2-yl)methyl)-1H-imidazol-5-yl)imidazo[1,2-b]pyridazine-3-carbonitrile

6-(4-(3-chloro-4-fluorophenyl)-1-(3-methyloxetan-3-yl)-1H-imidazol-5-yl)imidazo[1,2-b]pyridazine-3-carbonitrile

6-(4-(3-chloro-4-fluorophenyl)-1-(3-chloropropyl)-1H-imidazol-5-yl)imidazo[1,2-b]pyridazine-3-carbonitrile

6-(4-(3-chloro-4-fluorophenyl)-1-((3-methyloxetan-3-yl)methyl)-1H-imidazol-5-yl)imidazo[1,2-b]pyridazine-3-carbonitrile

6-(4-(3-chloro-4-fluorophenyl)-1-(tetrahydrofuran-3-yl)-1H-imidazol-5-yl)imidazo[1,2-b]pyridazine-3-carbonitrile

6-(4-(3-chloro-4-fluorophenyl)-1-(2-methoxyethyl)-1H-imidazol-5-yl)imidazo[1,2-b]pyridazine-3-carbonitrile

6-(4-(3-chloro-4-fluorophenyl)-1-(tetrahydro-2H-pyran-4-yl)-1H-imidazol-5-yl)imidazo[1,2-b]pyridazine-3-carbonitrile

6-(4-(3-chloro-4-fluorophenyl)-1-isopentyl-1H-imidazol-5-yl)imidazo[1,2-b]pyridazine-3-carbonitrile

6-(4-(3-chloro-4-fluorophenyl)-1-methyl-1H-imidazol-5-yl)imidazo[1,2-b]pyridazine-3-carbonitrile

6-(4-(3-chloro-4-fluorophenyl)-1-isopropyl-1H-imidazol-5-yl)imidazo[1,2-b]pyridazine-3-carbonitrile

6-(4-(3-chloro-4-fluorophenyl)-1-ethyl-1H-imidazol-5-yl)imidazo[1,2-b]pyridazine-3-carbonitrile

6-(4-(3-chloro-4-fluorophenyl)-1-(3,3-difluorocyclobutyl)-1H-imidazol-5-yl)imidazo[1,2-b]pyridazine-3-carbonitrile

6-(4-(3-chloro-4-fluorophenyl)-1-(3-fluoropropyl)-1H-imidazol-5-yl)imidazo[1,2-b]pyridazine-3-carbonitrile

6-(4-(3-chloro-4-fluorophenyl)-1-(3,3,3-trifluoro-2-hydroxypropyl)-1H-imidazol-5-yl)imidazo[1,2-b]pyridazine-3-carbonitrile

6-(4-(3-chloro-4-fluorophenyl)-1-(2,2-difluoropropyl)-1H-imidazol-5-yl)imidazo[1,2-b]pyridazine-3-carbonitrile

6-(4-(3-chloro-4-fluorophenyl)-1-(2-fluoro-2-methylpropyl)-1H-imidazol-5-yl)imidazo[1,2-b]pyridazine-3-carbonitrile

6-(4-(3-chloro-4-fluorophenyl)-1-cyclobutyl-1H-imidazol-5-yl)imidazo[1,2-b]pyridazine-3-carbonitrile

6-(1-(bicyclo[1.1.1]pentan-1-yl)-4-(3-chloro-4-fluorophenyl)-1H-imidazol-5-yl)imidazo[1,2-b]pyridazine-3-carbonitrile

6-(4-(3-chloro-4-fluorophenyl)-1-(2-chloroethyl)-1H-imidazol-5-yl)imidazo[1,2-b]pyridazine-3-carbonitrile

6-(4-(3-chloro-4-fluorophenyl)-1-(2-cyclopropylethyl)-1H-imidazol-5-yl)imidazo[1,2-b]pyridazine-3-carbonitrile

6-(4-(3-chloro-4-fluorophenyl)-1-((1-methylcyclopropyl)methyl)-1H-imidazol-5-yl)imidazo[1,2-b]pyridazine-3-carbonitrile

(R)-6-(4-(3-chloro-4-fluorophenyl)-1-(3,3-difluorocyclopentyl)-1H-imidazol-5-yl)imidazo[1,2-b]pyridazine-3-carbonitrile

(S)-6-(4-(3-chloro-4-fluorophenyl)-1-(3,3-difluorocyclopentyl)-1H-imidazol-5-yl)imidazo[1,2-b]pyridazine-3-carbonitrile

6-(1-cyclobutyl-4-(4-fluorophenyl)-1H-imidazol-5-yl)imidazo[1,2-a]pyridine-3-carbonitrile

6-(1-(3,3-difluorocyclobutyl)-4-(4-fluorophenyl)-1H-imidazol-5-yl)imidazo[1,2-a]pyridine-3-carbonitrile

6-(1-(sec-butyl)-4-(4-fluorophenyl)-1H-imidazol-5-yl)imidazo[1,2-a]pyridine-3-carbonitrile

(R)-6-(4-(4-fluorophenyl)-1-(2-hydroxypropyl)-1H-imidazol-5-yl)imidazo[1,2-a]pyridine-3-carbonitrile

6-(4-(4-fluorophenyl)-1-(3-hydroxybutyl)-1H-imidazol-5-yl)imidazo[1,2-a]pyridine-3-carbonitrile

6-(4-(4-fluorophenyl)-1-(2-hydroxybutyl)-1H-imidazol-5-yl)imidazo[1,2-a]pyridine-3-carbonitrile

(R)-6-(1-(2,3-dihydroxypropyl)-4-(4-fluorophenyl)-1H-imidazol-5-yl)imidazo[1,2-a]pyridine-3-carbonitrile

6-(1-(cyclobutylmethyl)-4-(4-fluorophenyl)-1H-imidazol-5-yl)imidazo[1,2-a]pyridine-3-carbonitrile

6-(1-ethyl-4-(4-fluorophenyl)-1H-imidazol-5-yl)imidazo[1,2-a]pyridine-3-carbonitrile

6-(4-(4-fluorophenyl)-1-(pentan-3-yl)-1H-imidazol-5-yl)imidazo[12-a]pyridine-3-carbonitrile

6-(4-(4-fluorophenyl)-1-(3-hydroxypropyl)-1H-imidazol-5-yl)imidazo[1,2-a]pyridine-3-carbonitrile

6-(4-(4-fluorophenyl)-1-(3-methylbutan-2-yl)-1H-imidazol-5-yl)imidazo[1,2-a]pyridine-3-carbonitrile

6-(1-cyclopropyl-4-(4-fluorophenyl)-1H-imidazol-5-yl)imidazo[1,2-a]pyridine-3-carbonitrile

6-(4-(4-fluorophenyl)-1-(oxetan-3-yl)-1H-imidazol-5-yl)imidazo[12-a]pyridine-3-carbonitrile

6-(4-(4-fluorophenyl)-1-isopropyl-1H-imidazol-5-yl)imidazo[1,2-a]pyridine-3-carbonitrile

6-(4-(4-fluorophenyl)-1-(4-hydroxybutan-2-yl)-1H-imidazol-5-yl)imidazo[1,2-a]pyridine-3-carbonitrile

6-(4-(4-fluorophenyl)-1-(1-hydroxypropan-2-yl)-1H-imidazol-5-yl)imidazo[1,2-a]pyridine-3-carbonitrile

6-(4-(4-fluorophenyl)-1-isobutyl-1H-imidazol-5-yl)imidazo[1,2-a]pyridine-3-carbonitrile

6-(4-(4-fluorophenyl)-1-(1-hydroxybutan-2-yl)-1H-imidazol-5-yl)imidazo[1,2-a]pyridine-3-carbonitrile

6-(4-(4-fluorophenyl)-1-(3-fluoropropyl)-1H-imidazol-5-yl)imidazo[12-a]pyridine-3-carbonitrile

6-(1-(1,3-dihydroxypropan-2-yl)-4-(4-fluorophenyl)-1H-imidazol-5-yl)imidazo[1,2-a]pyridine-3-carbonitrile

6-(1-cyclopentyl-4-(4-fluorophenyl)-1H-imidazol-5-yl)imidazo[1,2-a]pyridine-3-carbonitrile

6-(4-(4-fluorophenyl)-1-propyl-1H-imidazol-5-yl)imidazo[1,2-a]pyridine-3-carbonitrile

6-(1-(1-cyclopropylethyl)-4-(4-fluorophenyl)-1H-imidazol-5-yl)imidazo[12-a]pyridine-3-carbonitrile

(S)-6-(4-(4-fluorophenyl)-1-(2-hydroxypropyl)-1H-imidazol-5-yl)imidazo[1,2-a]pyridine-3-carbonitrile

6-(4-(4-fluorophenyl)-1-(2-hydroxy-2-methylpropyl)-1H-imidazol-5-yl)imidazo[1,2-a]pyridine-3-carbonitrile

6-(1-(2-ethoxyethyl)-4-(4-fluorophenyl)-1H-imidazol-5-yl)imidazo[1,2-a]pyridine-3-carbonitrile

(S)-6-(1-(2,3-dihydroxypropyl)-4-(4-fluorophenyl)-1H-imidazol-5-yl)imidazo[1,2-a]pyridine-3-carbonitrile

6-(4-(4-fluorophenyl)-1-(3,3,3-trifluoro-2-hydroxypropyl)-1H-imidazol-5-yl)imidazo[1,2-a]pyridine-3-carbonitrile

6-(4-(3-chloro-4-fluorophenyl)-1-ethyl-1H-imidazol-5-yl)imidazo[1,2-a]pyridine-3-carbonitrile

6-(4-(3-chloro-4-fluorophenyl)-1-(2-morpholinoethyl)-1H-imidazol-5-yl)imidazo[1,2-a]pyridine-3-carbonitrile

6-(4-(3-chloro-4-fluorophenyl)-1-(cyclopropylmethyl)-1H-imidazol-5-yl)imidazo[1,2-a]pyridine-3-carbonitrile

6-(4-(3-chloro-4-fluorophenyl)-1-(oxetan-3-yl)-1H-imidazol-5-yl)imidazo[1,2-a]pyridine-3-carbonitrile

6-(4-(3-chloro-4-fluorophenyl)-1-methyl-1H-imidazol-5-yl)imidazo[1,2-a]pyridine-3-carbonitrile

6-(4-(3-chloro-4-fluorophenyl)-1-(3,3-difluorocyclobutyl)-1H-imidazol-5-yl)imidazo[1,2-a]pyridine-3-carbonitrile

6-(4-(3-chloro-4-fluorophenyl)-1-(2-hydroxyethyl)-1H-imidazol-5-yl)imidazo[1,2-a]pyridine-3-carbonitrile

6-(4-(3-chloro-4-fluorophenyl)-1-(3-fluoropropyl)-1H-imidazol-5-yl)imidazo[1,2-a]pyridine-3-carbonitrile

6-(1-(3-fluorocyclobutyl)-4-(4-fluorophenyl)-1H-imidazol-5-yl)imidazo[1,2-b]pyridazine-3-carbonitrile

(S)-6-(1-(1-fluorobutan-2-yl)-4-(4-fluorophenyl)-1H-imidazol-5-yl)imidazo[1,2-b]pyridazine-3-carbonitrile

6-(4-(3-chloro-4-fluorophenyl)-1-(3-fluorocyclobutyl)-1H-imidazol-5-yl)imidazo[1,2-b]pyridazine-3-carbonitrile

6-(1-(2,2-difluoroethyl)-4-(4-fluorophenyl)-1H-imidazol-5-yl)imidazo[1,2-b]pyridazine-3-carboxamide

6-(1-(3,3-difluorocyclobutyl)-4-(4-fluorophenyl)-1H-imidazol-5-yl)imidazo[1,2-b]pyridazine-3-carboxamide

6-(4-(4-fluorophenyl)-1-(3,3,3-trifluoropropyl)-1H-imidazol-5-yl)imidazo[1,2-b]pyridazine-3-carboxamide

6-(1-(3,3-difluorocyclopentyl)-4-(4-fluorophenyl)-1H-imidazol-5-yl)imidazo[1,2-b]pyridazine-3-carboxamide

6-(1-cyclopropyl-4-(4-fluorophenyl)-1H-imidazol-5-yl)imidazo[1,2-b]pyridazine-3-carboxamide

6-(1-(4,4-difluorocyclohexyl)-4-(4-fluorophenyl)-1H-imidazol-5-yl)imidazo[1,2-b]pyridazine-3-carboxamide

6-(1-(2-fluoroethyl)-4-(4-fluorophenyl)-1H-imidazol-5-yl)imidazo[1,2-b]pyridazine-3-carboxamide

6-(1-ethyl-4-(4-fluorophenyl)-1H-imidazol-5-yl)imidazo[1,2-b]pyridazine-3-carboxamide

6-(4-(3-chloro-4-fluorophenyl)-1-(2,2-difluoroethyl)-1H-imidazol-5-yl)imidazo[1,2-b]pyridazine-3-carboxamide

6-(4-(3-chloro-4-fluorophenyl)-1-(2-fluoroethyl)-1H-imidazol-5-yl)imidazo[1,2-b]pyridazine-3-carboxamide

6-(4-(3-chloro-4-fluorophenyl)-1-(3,3,3-trifluoropropyl)-1H-imidazol-5-yl)imidazo[1,2-b]pyridazine-3-carboxamide

6-(4-(3-chloro-4-fluorophenyl)-1-isopropyl-1H-imidazol-5-yl)imidazo[1,2-b]pyridazine-3-carboxamide

6-(4-(3-chloro-4-fluorophenyl)-1-ethyl-1H-imidazol-5-yl)imidazo[1,2-b]pyridazine-3-carboxamide

6-(4-(3-chloro-4-fluorophenyl)-1-(3,3-difluorocyclobutyl)-1H-imidazol-5-yl)imidazo[1,2-b]pyridazine-3-carboxamide

6-(4-(3-chloro-4-fluorophenyl)-1-ethyl-1H-imidazol-5-yl)imidazo[1,2-a]pyridine-3-carboxamide

6-(4-(3-chloro-4-fluorophenyl)-1-(2-morpholinoethyl)-1H-imidazol-5-yl)imidazo[1,2-a]pyridine-3-carboxamide

6-(4-(3-chloro-4-fluorophenyl)-1-(3,3-difluorocyclobutyl)-1H-imidazol-5-yl)imidazo[1,2-a]pyridine-3-carboxamide

6-(4-(3-chloro-4-fluorophenyl)-1-(1,3-dihydroxypropan-2-yl)-1H-imidazol-5-yl)imidazo[1,2-a]pyridine-3-carboxamide

6-(4-(4-fluorophenyl)-1-cis-3-hydroxycyclobutyl)-1H-imidazol-5-yl)imidazo[1,2-b]pyridazine-3-carboxamide

6-(4-(4-fluorophenyl)-1-(2-isopropoxyethyl)-1H-imidazol-5-yl)imidazo[1,2-b]pyridazine-3-carboxamide

(S)-6-(4-(4-fluorophenyl)-1-(1-hydroxybutan-2-yl)-1H-imidazol-5-yl)imidazo[1,2-b]pyridazine-3-carboxamide

6-(4-(4-fluorophenyl)-1-(oxetan-3-yl)-1H-imidazol-5-yl)imidazo[1,2-b]pyridazine-3-carboxamide

6-(1-(3-fluorocyclobutyl)-4-(4-fluorophenyl)-1H-imidazol-5-yl)imidazo[1,2-b]pyridazine-3-carboxamide

(S)-6-(1-(1-fluorobutan-2-yl)-4-(4-fluorophenyl)-1H-imidazol-5-yl)imidazo[1,2-b]pyridazine-3-carboxamide

6-(1-(1,3-dihydroxypropan-2-yl)-4-(4-fluorophenyl)-1H-imidazol-5-yl)imidazo[1,2-b]pyridazine-3-carboxamide

6-(1-(1-cyclopropyl-2-methoxyethyl)-4-(4-fluorophenyl)-H-imidazol-5-yl)imidazo[1,2-b]pyridazine-3-carboxamide

6-(4-(4-fluorophenyl)-1-(3-hydroxy-3-methylbutyl)-1H-imidazol-5-yl)imidazo[1,2-b]pyridazine-3-carboxamide

6-(4-(4-fluorophenyl)-1-(3-hydroxypropyl)-1H-imidazol-5-yl)imidazo[1,2-b]pyridazine-3-carboxamide

6-(4-(4-fluorophenyl)-1-(2-hydroxyethyl)-1H-imidazol-5-yl)imidazo[1,2-b]pyridazine-3-carboxamide

6-(4-(4-fluorophenyl)-1-methyl-1H-imidazol-5-yl)imidazo[1,2-b]pyridazine-3-carboxamide

6-(4-(4-fluorophenyl)-1-isopropyl-1H-imidazol-5-yl)imidazo[1,2-b]pyridazine-3-carboxamide

6-(1-(bicyclo[1.1.1]pentan-1-yl)-4-(4-fluorophenyl)-1H-imidazol-5-yl)imidazo[1,2-b]pyridazine-3-carboxamide

6-(1-(2,2-difluoropropyl)-4-(4-fluorophenyl)-1H-imidazol-5-yl)imidazo[1,2-b]pyridazine-3-carboxamide

6-(4-(3-chloro-4-fluorophenyl)-1-(2-hydroxyethyl)-1H-imidazol-5-yl)imidazo[1,2-b]pyridazine-3-carboxamide

6-(4-(3-chloro-4-fluorophenyl)-1-(3-hydroxy-3-methylbutyl)-1H-imidazol-5-yl)imidazo[1,2-b]pyridazine-3-carboxamide

6-(4-(3-chloro-4-fluorophenyl)-1-((1s, 3s)-3-hydroxycyclobutyl)-1H-imidazol-5-yl)imidazo[1,2-b]pyridazine-3-carboxamide

6-(4-(3-chloro-4-fluorophenyl)-1-(3-fluorocyclobutyl)-1H-imidazol-5-yl)imidazo[1,2-b]pyridazine-3-carboxamide

6-(4-(3-chloro-4-fluorophenyl)-1-(3-hydroxypropyl)-1H-imidazol-5-yl)imidazo[1,2-b]pyridazine-3-carboxamide

6-(4-(3-chloro-4-fluorophenyl)-1-(2-(pyrrolidin-1-yl)ethyl)-1H-imidazol-5-yl)imidazo[1,2-b]pyridazine-3-carboxamide

6-(4-(3-chloro-4-fluorophenyl)-1-(tetrahydro-2H-pyran-4-yl)-1H-imidazol-5-yl)imidazo[1,2-b]pyridazine-3-carboxamide

(S)-6-(4-(3-chloro-4-fluorophenyl)-1-((tetrahydrofuran-2-yl)methyl)-1H-imidazol-5-yl)imidazo[1,2-b]pyridazine-3-carboxamide

6-(4-(3-chloro-4-fluorophenyl)-1-(tetrahydrofuran-3-yl)-1H-imidazol-5-yl)imidazo[1,2-b]pyridazine-3-carboxamide

6-(4-(3-chloro-4-fluorophenyl)-1-(2-methoxyethyl)-1H-imidazol-5-yl)imidazo[1,2-b]pyridazine-3-carboxamide

6-(4-(3-chloro-4-fluorophenyl)-1-isopentyl-1H-imidazol-5-yl)imidazo[1,2-b]pyridazine-3-carboxamide

6-(4-(3-chloro-4-fluorophenyl)-1-(3-chloropropyl)-1H-imidazol-5-yl)imidazo[1,2-b]pyridazine-3-carboxamide

6-(4-(3-chloro-4-fluorophenyl)-1-(2-cyclobutylethyl)-1H-imidazol-5-yl)imidazo[1,2-b]pyridazine-3-carboxamide

6-(4-(3-chloro-4-fluorophenyl)-1-(2,2-difluoropropyl)-1H-imidazol-5-yl)imidazo[1,2-b]pyridazine-3-carboxamide

6-(4-(4-fluorophenyl)-1-(1-hydroxypropan-2-yl)-1H-imidazol-5-yl)imidazo[1,2-a]pyridine-3-carboxamide

6-(4-(4-fluorophenyl)-1-(2-hydroxybutyl)-1H-imidazol-5-yl)imidazo[1,2-a]pyridine-3-carboxamide

6-(4-(4-fluorophenyl)-1-(4-hydroxybutan-2-yl)-1H-imidazol-5-yl)imidazo[1,2-a]pyridine-3-carboxamide

(R)-6-(4-(4-fluorophenyl)-1-(2-hydroxypropyl)-1H-imidazol-5-yl)imidazo[1,2-a]pyridine-3-carboxamide

6-(4-(4-fluorophenyl)-1-(3-hydroxybutyl)-1H-imidazol-5-yl)imidazo[1,2-a]pyridine-3-carboxamide

6-(1-(cyclobutylmethyl)-4-(4-fluorophenyl)-1H-imidazol-5-yl)imidazo[1,2-a]pyridine-3-carboxamide

(S)-6-(4-(4-fluorophenyl)-1-(2-hydroxypropyl)-1H-imidazol-5-yl)imidazo[1,2-a]pyridine-3-carboxamide

6-(1-cyclopentyl-4-(4-fluorophenyl)-1H-imidazol-5-yl)imidazo[1,2-a]pyridine-3-carboxamide

6-(1-ethyl-4-(4-fluorophenyl)-1H-imidazol-5-yl)imidazo[1,2-a]pyridine-3-carboxamide

(S)-6-(1-(2,3-dihydroxypropyl)-4-(4-fluorophenyl)-1H-imidazol-5-yl)imidazo[1,2-a]pyridine-3-carboxamide

6-(4-(4-fluorophenyl)-1-(3-fluoropropyl)-1H-imidazol-5-yl)imidazo[1,2-a]pyridine-3-carboxamide

6-(1-(3-(dimethylamino)propyl)-4-(4-fluorophenyl)-1H-imidazol-5-yl)imidazo[1,2-a]pyridine-3-carboxamide

(R)-6-(1-(2,3-dihydroxypropyl)-4-(4-fluorophenyl)-1H-imidazol-5-yl)imidazo[1,2-a]pyridine-3-carboxamide

6-(4-(4-fluorophenyl)-1-(3-hydroxypropyl)-1H-imidazol-5-yl)imidazo[1,2-a]pyridine-3-carboxamide

6-(4-(4-fluorophenyl)-1-(2-hydroxy-2-methylpropyl)-1H-imidazol-5-yl)imidazo[1,2-a]pyridine-3-carboxamide

6-(1-(1-cyclopropylethyl)-4-(4-fluorophenyl)-1H-imidazol-5-yl)imidazo[1,2-a]pyridine-3-carboxamide

6-(4-(4-fluorophenyl)-1-isobutyl-1H-imidazol-5-yl)imidazo[1,2-a]pyridine-3-carboxamide

6-(4-(4-fluorophenyl)-1-(3,3,3-trifluoro-2-hydroxypropyl)-1H-imidazol-5-yl)imidazo[1,2-a]pyridine-3-carboxamide

6-(4-(4-fluorophenyl)-1-isopropyl-1H-imidazol-5-yl)imidazo[1,2-a]pyridine-3-carboxamide

6-(1-(1,3-dihydroxypropan-2-yl)-4-(4-fluorophenyl)-1H-imidazol-5-yl)imidazo[1,2-a]pyridine-3-carboxamide

6-(1-cyclobutyl-4-(4-fluorophenyl)-1H-imidazol-5-yl)imidazo[1,2-a]pyridine-3-carboxamide

6-(4-(4-fluorophenyl)-1-(oxetan-3-yl)-1H-imidazol-5-yl)imidazo[1,2-a]pyridine-3-carboxamide

6-(1-(sec-butyl)-4-(4-fluorophenyl)-1H-imidazol-5-yl)imidazo[1,2-a]pyridine-3-carboxamide

6-(4-(4-fluorophenyl)-1-(1-hydroxypropan-2-yl)-1H-imidazol-5-yl)imidazo[1,2-a]pyridine-3-carboxamide

6-(4-(4-fluorophenyl)-1-(2-hydroxypropyl)-1H-imidazol-5-yl)imidazo[1,2-a]pyridine-3-carboxamide

6-(4-(4-fluorophenyl)-1-propyl-1H-imidazol-5-yl)imidazo[1,2-a]pyridine-3-carboxamide

6-(1-(2-ethoxyethyl)-4-(4-fluorophenyl)-1H-imidazol-5-yl)imidazo[1,2-a]pyridine-3-carboxamide

6-(4-(4-fluorophenyl)-1-(1-hydroxybutan-2-yl)-1H-imidazol-5-yl)imidazo[1,2-a]pyridine-3-carboxamide

6-(1-(3,3-difluorocyclobutyl)-4-(4-fluorophenyl)-1H-imidazol-5-yl)imidazo[1,2-a]pyridine-3-carboxamide

6-(4-(3-chloro-4-fluorophenyl)-1-methyl-1H-imidazol-5-yl)imidazo[1,2-a]pyridine

6-(4-(3-chloro-4-fluorophenyl)-1-(3,3,3-trifluoropropyl)-1H-imidazol-5-yl)imidazo[1,2-a]pyridine

6-(4-(3-chloro-4-fluorophenyl)-1-(3-fluoropropyl)-1H-imidazol-5-yl)imidazo[1,2-a]pyridine

6-(4-(3-chloro-4-fluorophenyl)-1-(3,3-difluorocyclobutyl)-1H-imidazol-5-yl)imidazo[1,2-a]pyridine

(R)-6-(4-(3-chloro-4-fluorophenyl)-1-(3,3-difluorocyclopentyl)-1H-imidazol-5-yl)imidazo[1,2-a]pyridine

(S)-6-(4-(3-chloro-4-fluorophenyl)-1-(3,3-difluorocyclopentyl)-1H-imidazol-5-yl)imidazo[1,2-a]pyridine

6-(4-(3-chloro-4-fluorophenyl)-1-(2-fluoroethyl)-1H-imidazol-5-yl)imidazo[1,2-a]pyridine

1-(4-(4-fluorophenyl)-5-(imidazo[1,2-b]pyridazin-6-yl)-1H-imidazol-1-yl)cyclopropanecarbonitrile

6-(1-(1-(difluoromethyl)cyclopropyl)-4-(4-fluorophenyl)-1H-imidazol-5-yl)imidazo[1,2-b]pyridazine

methyl 3-(5-(3-cyanoimidazo[1,2-b]pyridazin-6-yl)-4-(4-fluorophenyl)-1H-imidazol-1-yl)azetidine-1-carboxylate

6-(1-(1-acetylazetidin-3-yl)-4-(4-fluorophenyl)-1H-imidazol-5-yl)imidazo[1,2-b]pyridazine-3-carbonitrile

6-(1-(1-(cyclopropanecarbonyl)azetidin-3-yl)-4-(4-fluorophenyl)-1H-imidazol-5-yl)imidazo[1,2-b]pyridazine-3-carbonitrile

N-(tert-butyl)-3-(5-(3-cyanoimidazo[1,2-b]pyridazin-6-yl)-4-(4-fluorophenyl)-1H-imidazol-1-yl)azetidine-1-carboxamide

6-(1-(1-(cyanomethyl)azetidin-3-yl)-4-(4-fluorophenyl)-1H-imidazol-5-yl)imidazo[1,2-b]pyridazine-3-carbonitrile

6-(1-(1-(tert-butylcarbamoyl)azetidin-3-yl)-4-(4-fluorophenyl)-1H-imidazol-5-yl)imidazo[1,2-b]pyridazine-3-carboxamide

(6-(1-(2,2-difluoroethyl)-4-(4-fluorophenyl)-1H-imidazol-5-yl)imidazo[1,2-b]pyridazin-3-yl)methanamine

N-((6-(1-(2,2-difluoroethyl)-4-(4-fluorophenyl)-1H-imidazol-5-yl)imidazo[1,2-b]pyridazin-3-yl)methyl)acetamide

N-((6-(1-(2,2-difluoroethyl)-4-(4-fluorophenyl)-1H-imidazol-5-yl)imidazo[1,2-b]pyridazin-3-yl)methyl)cyclopropanecarboxamide

1-(tert-butyl)-3-((6-(1-(2,2-difluoroethyl)-4-(4-fluorophenyl)-1H-imidazol-5-yl)imidazo[1,2-b]pyridazin-3-yl)methyl)urea

methyl ((6-(1-(2,2-difluoroethyl)-4-(4-fluorophenyl)-1H-imidazol-5-yl)imidazo[1,2-b]pyridazin-3-yl)methyl)carbamate

isopropyl ((6-(1-(2,2-difluoroethyl)-4-(4-fluorophenyl)-1H-imidazol-5-yl)imidazo[1,2-b]pyridazin-3-yl)methyl)carbamate

N-((6-(1-(2,2-difluoroethyl)-4-(4-fluorophenyl)-1H-imidazol-5-yl)imidazo[1,2-b]pyridazin-3-yl)methyl)pivalamide

6-(1-(2,2-difluoroethyl)-4-(4-fluorophenyl)-1H-imidazol-5-yl)-N-hydroxyimidazo[1,2-b]pyridazine-3-carboximidamide

2-(6-(1-(2,2-difluoroethyl)-4-(4-fluorophenyl)-1H-imidazol-5-yl)imidazo[1,2-b]pyridazin-3-yl)propan-2-ol

6-(1-(2,2-difluoroethyl)-4-(4-fluorophenyl)-1H-imidazol-5-yl)imidazo[1,2-b]pyridazine-3-carbohydrazide

6-(1-(2,2-difluoroethyl)-4-(4-fluorophenyl)-1H-imidazol-5-yl)-N-methylimidazo[1,2-b]pyridazine-3-carboxamide

6-(1-(2,2-difluoroethyl)-4-(4-fluorophenyl)-1H-imidazol-5-yl)-N,N-dimethylimidazo[1,2-b]pyridazine-3-carboxamide

N-cyclopropyl-6-(1-(2,2-difluoroethyl)-4-(4-fluorophenyl)-1H-imidazol-5-yl)imidazo[1,2-b]pyridazine-3-carboxamide

6-(1-(2,2-difluoroethyl)-4-(4-fluorophenyl)-1H-imidazol-5-yl)-N-methoxyimidazo[1,2-b]pyridazine-3-carboxamide

(6-(1-(2,2-difluoroethyl)-4-(4-fluorophenyl)-1H-imidazol-5-yl)imidazo[1,2-b]pyridazin-3-yl)methanol

methyl (6-(1-(2,2-difluoroethyl)-4-(4-fluorophenyl)-1H-imidazol-5-yl)imidazo[1,2-b]pyridazin-3-yl)carbamate

N-(6-(1-(2,2-difluoroethyl)-4-(4-fluorophenyl)-1H-imidazol-5-yl)imidazo[1,2-b]pyridazin-3-yl)acetamide

1-(6-(1-(2,2-difluoroethyl)-4-(4-fluorophenyl)-1H-imidazol-5-yl)imidazo[1,2-b]pyridazin-3-yl)-2,2,2-trifluoroethanol

1-(6-(1-(2,2-difluoroethyl)-4-(4-fluorophenyl)-1H-imidazol-5-yl)imidazo[1,2-b]pyridazin-3-yl)ethanol

6-(1-(2,2-difluoroethyl)-4-(4-fluorophenyl)-1H-imidazol-5-yl)-3-(difluoromethyl) imidazo[1,2-b]pyridazine

5-(6-(1-(2,2-difluoroethyl)-4-(4-fluorophenyl)-1H-imidazol-5-yl)imidazo[1,2-b]pyridazin-3-yl)oxazole

2-(6-(1-(2,2-difluoroethyl)-4-(4-fluorophenyl)-1H-imidazol-5-yl)imidazo[1,2-b]pyridazin-3-yl)ethanol

6-(1-(2,2-difluoroethyl)-4-(4-fluorophenyl)-1H-imidazol-5-yl)imidazo[1,2-a]pyridine

6-(4-(3-chloro-4-fluorophenyl)-1-(2,2-difluoroethyl)-1H-imidazol-5-yl)imidazo[1,2-a]pyridine

6-(1-(2,2-difluoroethyl)-4-(3,4-difluorophenyl)-1H-imidazol-5-yl)imidazo[1,2-a]pyridine

6-(1-(2,2-difluoroethyl)-4-(2,4-difluorophenyl)-1H-imidazol-5-yl)imidazo[1,2-a]pyridine

6-(4-(5-chloro-2-fluorophenyl)-1-(2,2-difluoroethyl)-1H-imidazol-5-yl)imidazo[1,2-a]pyridine

6-(4-(5-chloro-2,4-difluorophenyl)-1-(2,2-difluoroethyl)-1H-imidazol-5-yl)imidazo[1,2-a]pyridine

6-(1-(2,2-difluoroethyl)-4-(4-fluorophenyl)-1H-imidazol-5-yl)imidazo[1,2-a]pyridine-3-carbonitrile

6-(4-(3-chloro-4-fluorophenyl)-1-(2,2-difluoroethyl)-1H-imidazol-5-yl)imidazo[1,2-a]pyridine-3-carbonitrile

6-(1-(2,2-difluoroethyl)-4-(3,4-difluorophenyl)-1H-imidazol-5-yl)imidazo[1,2-a]pyridine-3-carbonitrile

6-(1-(2,2-difluoroethyl)-4-(2,4-difluorophenyl)-1H-imidazol-5-yl)imidazo[1,2-a]pyridine-3-carbonitrile

6-(4-(5-chloro-2-fluorophenyl)-1-(2,2-difluoroethyl)-1H-imidazol-5-yl)imidazo[1,2-a]pyridine-3-carbonitrile

6-(4-(5-chloro-2,4-difluorophenyl)-1-(2,2-difluoroethyl)-1H-imidazol-5-yl)imidazo[1,2-a]pyridine-3-carbonitrile

6-(1-(2,2-difluoroethyl)-4-(4-fluorophenyl)-1H-imidazol-5-yl)imidazo[1,2-a]pyridine-3-carboxamide

6-(4-(3-chloro-4-fluorophenyl)-1-(2,2-difluoroethyl)-1H-imidazol-5-yl)imidazo[1,2-a]pyridine-3-carboxamide

6-(1-(2,2-difluoroethyl)-4-(3,4-difluorophenyl)-1H-imidazol-5-yl)imidazo[1,2-a]pyridine-3-carboxamide

6-(1-(2,2-difluoroethyl)-4-(2,4-difluorophenyl)-1H-imidazol-5-yl)imidazo[1,2-a]pyridine-3-carboxamide

6-(4-(5-chloro-2-fluorophenyl)-1-(2,2-difluoroethyl)-1H-imidazol-5-yl)imidazo[1,2-a]pyridine-3-carboxamide

6-(4-(5-chloro-2,4-difluorophenyl)-1-(2,2-difluoroethyl)-1H-imidazol-5-yl)imidazo[1,2-a]pyridine-3-carboxamide

6-(4-(3-cyanophenyl)-1-(2,2-difluoroethyl)-1H-imidazol-5-yl)imidazo[1,2-b]pyridazine-3-carbonitrile

6-(1-(2,2-difluoroethyl)-4-phenyl-1H-imidazol-5-yl)imidazo[1,2-b]pyridazine-3-carbonitrile

6-(4-(3,5-dichlorophenyl)-1-(2,2-difluoroethyl)-1H-imidazol-5-yl)imidazo[1,2-b]pyridazine-3-carbonitrile

N-(2-(5-(3-cyanoimidazo[1,2-b]pyridazin-6-yl)-1-(2,2-difluoroethyl)-1H-imidazol-4-yl)phenyl)methanesulfonamide

6-(4-(3-aminophenyl)-1-(2,2-difluoroethyl)-1H-imidazol-5-yl)imidazo[1,2-b]pyridazine-3-carbonitrile

6-(1-(2,2-difluoroethyl)-4-(p-tolyl)-1H-imidazol-5-yl)imidazo[1,2-b]pyridazine-3-carbonitrile

6-(1-(2,2-difluoroethyl)-4-(4-methoxyphenyl)-1H-imidazol-5-yl)imidazo[1,2-b]pyridazine-3-carbonitrile

6-(1-(2,2-difluoroethyl)-4-(3-(trifluoromethyl)phenyl)-1H-imidazol-5-yl)imidazo[1,2-b]pyridazine-3-carbonitrile

6-(1-(2,2-difluoroethyl)-4-(4-(trifluoromethyl)phenyl)-1H-imidazol-5-yl)imidazo[1,2-b]pyridazine-3-carbonitrile

N-(3-(5-(3-cyanoimidazo[1,2-b]pyridazin-6-yl)-1-(2,2-difluoroethyl)-1H-imidazol-4-yl)phenyl)acetamide

6-(1-(2,2-difluoroethyl)-4-(2-(trifluoromethyl)phenyl)-1H-imidazol-5-yl)imidazo[1,2-b]pyridazine-3-carbonitrile

6-(1-(2,2-difluoroethyl)-4-(2-hydroxyphenyl)-1H-imidazol-5-yl)imidazo[1,2-b]pyridazine-3-carbonitrile

6-(1-(2,2-difluoroethyl)-4-(3-hydroxyphenyl)-1H-imidazol-5-yl)imidazo[1,2-b]pyridazine-3-carbonitrile

6-(1-(2,2-difluoroethyl)-4-(4-hydroxyphenyl)-1H-imidazol-5-yl)imidazo[1,2-b]pyridazine-3-carbonitrile

2-(5-(3-cyanoimidazo[1,2-b]pyridazin-6-yl)-1-(2,2-difluoroethyl)-1H-imidazol-4-yl)benzamide

N-(3-(5-(3-cyanoimidazo[1,2-b]pyridazin-6-yl)-1-(2,2-difluoroethyl)-1H-imidazol-4-yl)phenyl)methanesulfonamide

6-(1-(2,2-difluoroethyl)-4-(2-(hydroxymethyl)phenyl)-1H-imidazol-5-yl)imidazo[1,2-b]pyridazine-3-carbonitrile

6-(1-(2,2-difluoroethyl)-4-(3-(methylsulfonyl)phenyl)-1H-imidazol-5-yl)imidazo[1,2-b]pyridazine-3-carbonitrile

3-(5-(3-cyanoimidazo[1,2-b]pyridazin-6-yl)-1-(2,2-difluoroethyl)-1H-imidazol-4-yl)benzamide

6-(1-(2,2-difluoroethyl)-4-(3-(hydroxymethyl)phenyl)-1H-imidazol-5-yl)imidazo[1,2-b]pyridazine-3-carbonitrile

6-(4-([1,1′-biphenyl]-3-yl)-1-(2,2-difluoroethyl)-1H-imidazol-5-yl)imidazo[1,2-b]pyridazine-3-carbonitrile

6-(4-(4-cyanophenyl)-1-(2,2-difluoroethyl)-1H-imidazol-5-yl)imidazo[1,2-b]pyridazine-3-carbonitrile

6-(1-(2,2-difluoroethyl)-4-(3-(trifluoromethoxy)phenyl)-1H-imidazol-5-yl)imidazo[12-b]pyridazine-3-carbonitrile

6-(1-(2,2-difluoroethyl)-4-(4-fluoro-3-(trifluoromethyl)phenyl)-1H-imidazol-5-yl)imidazo[1,2-b]pyridazine-3-carbonitrile

6-(1-(2,2-difluoroethyl)-4-(4-fluoro-2-(trifluoromethyl)phenyl)-1H-imidazol-5-yl)imidazo[1,2-b]pyridazine-3-carbonitrile

6-(1-(2,2-difluoroethyl)-4-(4-fluoro-3-methoxyphenyl)-1H-imidazol-5-yl)imidazo[1,2-b]pyridazine-3-carbonitrile

6-(1-(2,2-difluoroethyl)-4-(4-isopropoxyphenyl)-1H-imidazol-5-yl)imidazo[1,2-b]pyridazine-3-carbonitrile

6-(4-(4-aminophenyl)-1-(2,2-difluoroethyl)-1H-imidazol-5-yl)imidazo[1,2-b]pyridazine-3-carbonitrile

6-(1-(2,2-difluoroethyl)-4-(3-(2-hydroxypropan-2-yl)phenyl)-1H-imidazol-5-yl)imidazo[1,2-b]pyridazine-3-carbonitrile

6-(4-(3-cyano-4-fluorophenyl)-1-(2,2-difluoroethyl)-1H-imidazol-5-yl)imidazo[1,2-b]pyridazine-3-carbonitrile

6-(1-(1-cyanocyclopropyl)-4-(4-fluorophenyl)-1H-imidazol-5-yl)imidazo[1,2-b]pyridazine-3-carbonitrile

6-(1-(2-cyanoethyl)-4-(4-fluorophenyl)-1H-imidazol-5-yl)imidazo[1,2-b]pyridazine-3-carbonitrile

6-(4-(4-fluorophenyl)-1-((1r, 3s, 5R, 7S)-3-hydroxyadamantan-1-yl)-1H-imidazol-5-yl)imidazo[1,2-b]pyridazine-3-carbonitrile

6-(4-(4-fluorophenyl)-1-neopentyl-1H-imidazol-5-yl)imidazo[1,2-b]pyridazine-3-carbonitrile

6-(1-(2,2-difluoroethyl)-4-(4-fluorophenyl)-2-methyl-1H-imidazol-5-yl)imidazo[1,2-a]pyridine

6-(1-(2,2-difluoroethyl)-4-(4-fluorophenyl)-2-methyl-1H-imidazol-5-yl)imidazo[1,2-a]pyridine-3-carboxamide

5-(1-(2,2-difluoroethyl)-4-(4-fluorophenyl)-2-methyl-1H-imidazol-5-yl)-1H-indazole

1-(6-(1-(2,2-difluoroethyl)-4-(4-fluorophenyl)-1H-imidazol-5-yl)imidazo[12-a]pyridin-3-yl)ethanol

N-((6-(1-(2,2-difluoroethyl)-4-(4-fluorophenyl)-1H-imidazol-5-yl)imidazo[1,2-a]pyridin-3-yl)methyl)-2,2-difluoroethanamine

N-((6-(1-(2,2-difluoroethyl)-4-(4-fluorophenyl)-1H-imidazol-5-yl)imidazo[12-a]pyridin-3-yl)methyl)-3,3-difluorocyclobutanamine

6-(1-(2,2-difluoroethyl)-4-(4-fluorophenyl)-1H-imidazol-5-yl)-3-(difluoromethyl)imidazo [1,2-a]pyridine

1-(6-(1-(2,2-difluoroethyl)-4-(4-fluorophenyl)-1H-imidazol-5-yl)imidazo[12-a]pyridin-3-yl)ethanol

N-cyclopropyl-6-(1-(2,2-difluoroethyl)-4-(4-fluorophenyl)-1H-imidazol-5-yl)imidazo[1,2-a]pyridine-3-carboxamide

N-(2-amino-2-oxoethyl)-6-(1-(2,2-difluoroethyl)-4-(4-fluorophenyl)-1H-imidazol-5-yl)imidazo[1,2-a]pyridine-3-carboxamide

6-(1-(2,2-difluoroethyl)-4-(4-fluorophenyl)-1H-imidazol-5-yl)-[1,2,4]triazolo[4,3-a]pyridine

7-(1-(2,2-difluoroethyl)-4-(4-fluorophenyl)-1H-imidazol-5-yl)-[1,2,4]triazolo[1,5-a]pyridine

6-(2-(4-fluorophenyl)-6,7-dihydro-5H-pyrrolo[1,2-a]imidazol-3-yl)imidazo[1,2-a]pyridine-3-carboxamide

methyl (6-(1-(2,2-difluoroethyl)-4-(4-fluorophenyl)-1H-imidazol-5-yl)imidazo[1,2-a]pyridin-3-yl)carbamate

3-cyclopropyl-6-(1-(2,2-difluoroethyl)-4-(4-fluorophenyl)-1H-imidazol-5-yl)imidazo[1,2-a]pyridine

2-(6-(1-ethyl-4-(4-fluorophenyl)-1H-imidazol-5-yl)imidazo[1,2-b]pyridazin-3-yl)propan-2-ol

2-(6-(1-cyclopropyl-4-(4-fluorophenyl)-1H-imidazol-5-yl)imidazo[1, 2-b]pyridazin-3-yl)propan-2-ol

6-(1-(2,2-difluoroethyl)-4-(4-fluorophenyl)-1H-imidazol-5-yl)-3-fluoroimidazo[1,2-a]pyridine

4-(6-(1-(2,2-difluoroethyl)-4-(4-fluorophenyl)-1H-imidazol-5-yl)imidazo[1,2-a]pyridin-3-yl)morpholine

N-(4-(4-fluorophenyl)-5-(imidazo[1,2-a]pyridin-6-yl)-1H-imidazol-2-yl)acetamide

1-(2,2-difluoroethyl)-4-(4-fluorophenyl)-5-(imidazo[1,2-a]pyridin-6-yl)-1H-imidazol-2-amine

N-(5-(3-cyanoimidazo[1,2-a]pyridin-6-yl)-1-(2,2-difluoroethyl)-4-(4-fluorophenyl)-1H-imidazol-2-yl)acetamide

6-(2-amino-1-(2,2-difluoroethyl)-4-(4-fluorophenyl)-1H-imidazol-5-yl)imidazo[1,2-a]pyridine-3-carbonitrile

6-(1-(azetidin-3-yl)-4-(4-fluorophenyl)-1H-imidazol-5-yl)imidazo[1,2-b]pyridazine-3-carbonitrile

tert-butyl 3-(5-(3-carbamoylimidazo[1,2-b]pyridazin-6-yl)-4-(4-fluorophenyl)-1H-imidazol-1-yl)azetidine-1-carboxylate

6-(1-(azetidin-3-yl)-4-(4-fluorophenyl)-1H-imidazol-5-yl)imidazo[1,2-b]pyridazine-3-carboxamide

(6-(1-(2,2-difluoroethyl)-4-(4-fluorophenyl)-1H-imidazol-5-yl)imidazo[1,2-b]pyridazin-3-yl)methanamine

6-(1-(2,2-difluoroethyl)-4-(4-fluorophenyl)-1H-imidazol-5-yl)-3-vinylimidazo[1,2-b]pyridazine

6-(1-(2,2-difluoroethyl)-4-(4-fluorophenyl)-2-methyl-1H-imidazol-5-yl)imidazo[1,2-a]pyridine-3-carbonitrile

ethyl 6-(1-(2,2-difluoroethyl)-4-(4-fluorophenyl)-1H-imidazol-5-yl)imidazo[1,2-a]pyridine-3-carboxylate

(6-(1-(2,2-difluoroethyl)-4-(4-fluorophenyl)-1H-imidazol-5-yl)imidazo[1,2-a]pyridin-3-yl)methanol

6-(2-(4-fluorophenyl)-6,7-dihydro-5H-pyrrolo[1,2-a]imidazol-3-yl)imidazo[1,2-a]pyridine-3-carbonitrile or

6-(1-(2,2-difluoroethyl)-4-(4-fluorophenyl)-1H-imidazol-5-yl)imidazo[1,2-a]pyridin-3-amine

or a pharmaceutically acceptable salt thereof.

13. The compound according to claim 1 having the structure of formula (II°),

or a pharmaceutically acceptable salt thereof,

wherein

R′ is hydrogen, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, —(C 0 -C 12 alkyl)-Cycloalkyl or —(C 0 -C 6 alkyl)-Heterocycloalkyl, each optionally substituted with 1 to 3 moieties that are each independently C 1 -C 6 alkyl, halogen, C 1 -C 6 haloalkyl, C 1 -C 6 alkyl-OR S0 , —OR S0 , —R S0 or cyano;

wherein each R S0 is independently hydrogen, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, —(C 0 -C 6 alkyl)-Aryl, —(C 0 -C 6 alkyl)-Heteroaryl, —(C 0 -C 6 alkyl)-Cycloalkyl, or —(C 0 -C 6 alkyl)-Heterocycloalkyl, wherein Aryl, Heteroaryl, Cycloalkyl, Heterocycloalkyl, alkyl, and haloalkyl are optionally substituted with C 1 -C 6 alkyl, halogen, C 1 -C 6 haloalkyl or cyano;

R 1 is hydrogen or C 1 -C 6 alkyl;

each R 2 is independently hydrogen, halogen, —C 1 -C 6 alkyl, —C 1 -C 6 alkyl-OR S2 or —OR S2 ;

Z is

a fused bicyclic ring of the formula,

wherein

ring A is 6-membered Heteroaryl, and

ring B is a 5-membered Heteroaryl; and

Z is optionally substituted by one or two —R Z groups that are each independently halogen, cyano, C 1-6 alkyl, C 1-6 alkenyl, C 1-6 haloalkyl, —C 1 -C 6 alkoxy, —(C 0 -C 6 alkyl)-Heteroaryl, —(C 0 -C 6 alkyl)-Heterocycloalkyl, —OR S3 , —SR S3 , —NR S3 2 , —C(O)R S3 , —C(O)OR S3 , —C(O)NR S3 2 , —C(NR S3 )NR S3 OR S3 , —S(O) 2 NR S3 2 , —S(O) 2 R S3 , —OC(O)R S3 , —N(R S3 )C(O)R S3 , —OC(O)OR S3 , —OC(O)NR S3 2 , —N(R S3 )C(O)OR 3 , —N(R S3 )C(O)NR S3 2 , —N(R S3f )S(O) 2 R S3 , —OP(O)(OR S3 ) 2 or —CH 2 —OP(O)(OR S3 ), wherein each alkyl, haloalkyl and alkoxy is optionally substituted by one or two —R Z2 groups;

14. A compound according to claim 1 having the structure of formula (III°),

or a pharmaceutically acceptable salt thereof,

wherein

wherein each R S0 is independently hydrogen, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, —(C 0 -C 6 alkyl)-Aryl, —(C 0 -C 6 alkyl)-Heteroaryl, —(C 0 -C 6 alkyl)-Cycloalkyl, or —(C 0 -C 6 alkyl)-Heterocycloalkyl, wherein Aryl, Heteroaryl, Cycloalkyl, Heterocycloalkyl, alkyl, and haloalkyl are optionally substituted with C 1 -C 6 alkyl, halogen, C 1 -C 6 haloalkyl or cyano;

R 1 is hydrogen or C 1 -C 6 alkyl;

each R 2 is independently hydrogen, halogen, —C 1 -C 6 alkyl, —C 1 -C 6 alkyl-OR S2 or —OR S2 ; and

R Z is halogen, cyano, C 1 -6alkyl, C 1 -6alkenyl, C 1 -6haloalkyl, —C 1 -C 6 alkoxy, —(C 0 -C 6 alkyl)-Heteroaryl, —(C 0 -C 6 alkyl)-Heterocycloalkyl, —OR S3 , —SR S3 , —NR S3 2 , —C(O)R S3 , —C(O)OR S3 , —C(O)NR S3 2 , —C(NR S3 )NR S3 R S3 , —S(O) 2 NR S3 2 , —S(O) 2 R S3 , —OC(O)R S3 , —N(R S3 )C(O)R S3 , —OC(O)OR S3 , —OC(O)NR S3 2 , —N(R S3 )C(O)OR S3 , —N(R S3 )C(O)NR S3 2 , —N(R S3f )S(O) 2 R S3 , —OP(O)(OR S3 ) 2 or —CH 2 —OP(O)(OR S3 ), wherein each alkyl, haloalkyl and alkoxy is optionally substituted by one or two —R Z2 groups;

each —R Z2 is independently halogen, cyano, C 1 -6alkyl, C 1 -6haloalkyl, —C 1 -C 6 alkoxy, —OR S4 , —SR S4 , —NR S4 2 , —C(O)R S4 , —C(O)OR S4 , —C(O)NR S4 2 , —S(O) 2 NR S4 2 , —S(O) 2 R S4 , —OC(O)R S4 , —N(R S4 )C(O)R S4 , —OC(O)OR S4 , —OC(O)NR S4 2 , —N(R S4 )C(O)OR S4 , —N(R S4 )C(O)NR S4 2 , —N(R S4 )S(O) 2 R S4 , —OP(O)(OR S4 ) 2 or —CH 2 —OP(O)(OR S4 ); and

15. A method of inhibiting TGF-β comprising contacting the TGF-β with a compound according to claim 1 .

16. A pharmaceutical composition comprising a pharmaceutically acceptable diluent, carrier, or excipient and a compound according to claim 12 .

17. A pharmaceutical composition comprising a pharmaceutically acceptable diluent, carrier, or excipient and a compound according to claim 14 .

18. The compound according to claim 1 of formula

19. The compound according to claim 1 wherein Z is optionally substituted

20. The compound according to claim 1 wherein A′ is phenyl substituted with one or two R 2 groups.

21. The compound according to claim 20 wherein R 2 is halogen.

22. A pharmaceutical composition comprising a pharmaceutically acceptable diluent, carrier, or excipient and the compound according to claim 19 .

23. The compound according to claim 1 that is 6-(4-(4-fluorophenyl)-1-cis-3-hydroxycyclobutyl)-1H-imidazol-5-yl)imidazo[1,2-b]pyridazine-3-carbonitrile,

or a pharmaceutically acceptable salt thereof.

24. A pharmaceutical composition comprising a pharmaceutically acceptable diluent, carrier, or excipient and the compound according to claim 23 .

25. The compound according to claim 1 that is 6-(4-(4-fluorophenyl)-1-(3-hydroxy-3-methylbutyl)-1H-imidazol-5-yl)imidazo[1,2-b]pyridazine-3-carbonitrile,

or a pharmaceutically acceptable salt thereof.

26. A pharmaceutical composition comprising a pharmaceutically acceptable diluent, carrier, or excipient and the compound according to claim 25 .

27. The compound according to claim 1 that is 6-(4-(4-fluorophenyl)-1-(2-hydroxyethyl)-1H-imidazol-5-yl)imidazo[1,2-b]pyridazine-3-carbonitrile,

or a pharmaceutically acceptable salt thereof.

28. A pharmaceutical composition comprising a pharmaceutically acceptable diluent, carrier, or excipient and the compound according to claim 27 .

29. The compound according to claim 1 that is 6-(4-(4-fluorophenyl)-1-isopropyl-1H-imidazol-5-yl)imidazo[1,2-b]pyridazine-3-carbonitrile,

or a pharmaceutically acceptable salt thereof.

30. A pharmaceutical composition comprising a pharmaceutically acceptable diluent, carrier, or excipient and the compound according to claim 29 .

31. The compound according to claim 1 that is 6-(4-(3-chloro-4-fluorophenyl)-1-(2-hydroxyethyl)-1H-imidazol-5-yl)imidazo[1,2-b]pyridazine-3-carbonitrile,

or a pharmaceutically acceptable salt thereof.

32. A pharmaceutical composition comprising a pharmaceutically acceptable diluent, carrier, or excipient and the compound according to claim 31 .

33. The compound according to claim 1 that is 6-(1-(2,2-difluoroethyl)-4-(4-fluorophenyl)-1H-imidazol-5-yl)imidazo[1,2-b]pyridazine-3-carboxamide,

or a pharmaceutically acceptable salt thereof.

34. A pharmaceutical composition comprising a pharmaceutically acceptable diluent, carrier, or excipient and the compound according to claim 33 .

35. The compound according to claim 1 that is 2-(6-(1-(2,2-difluoroethyl)-4-(4-fluorophenyl)-1H-imidazol-5-yl)imidazo[1,2-b]pyridazin-3-yl)propan-2-ol,

or a pharmaceutically acceptable salt thereof.

36. A pharmaceutical composition comprising a pharmaceutically acceptable diluent, carrier, or excipient and the compound according to claim 35 .

Assignments (5)

SECURITY INTEREST Recorded Aug 25, 2022

From: RIGEL PHARMACEUTICALS, INC.

To: MIDCAP FINANCIAL TRUST

Reel/Frame 061327/0712 →

ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Oct 10, 2017

From: YU, JIAXIN; KINSELLA, TODD; GELMAN, MARINA; HONG, HUI; DARWISH, IHAB S; SINGH, RAJINDER

To: RIGEL PHARMACEUTICALS, INC.

Reel/Frame 043826/0358 →

ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Aug 24, 2016