US 8,507,488 B2Granted

Fused nitrogen containing heterocycles and compositions thereof as kinase inhibitors

AssigneeIrm LLC

InventorsPamela A. Albaugh, Ha-Soon Choi, Gregory Chopiuk, Yi Fan, Paul Vincent Rucker, Zhicheng Wang

Life of this patent

Estimating the term…

Abstract

The invention provides compounds, pharmaceutical compositions comprising such compounds and methods of using such compounds to treat or prevent diseases or disorders associated with abnormal or deregulated kinase activity, particularly Ros, KDR, FMS, C-FMS, FLT3, c-Kit, JAK2, JAK3, Aurora, PDGFR, Lck, TrkA, TrkB, TrkC, IGF-IR, ALK4, ALK5 and ALK or combinations thereof.

Claims15

Dependent claims

A compound of Formula (I), or a pharmaceutically acceptable salt thereof:

wherein:
X1 and X2 are N, and X3 and X4 are C;
wherein k is 1, 2 or 3;
each R3 is independently selected from halogen, C1-C8alkyl, C6-C14aryl, and C2-C13heteroaryl,
wherein the C1-C8alkyl, C6-C14aryl, and C2-C13heteroaryl of R3 are optionally substituted with 1 to 3 substituents independently selected from halogen, hydroxyl, cyano, —OR9, C1-C8alkyl, hydroxyl-C1-C8alkyl, halo-substituted-C1-C8alkyl and C3-C8cycloalkyl;
R2 is C6-C14aryl, C2-C13heteroaryl or C2-C14heterocycloalkyl,
wherein the C6-C14aryl, C2-C13heteroaryl or C2-C14heterocycloalkyl of R2 are substituted with 1 substituents independently selected from —R6 and —Y1R6;
and the C6-C14aryl, C2-C13heteroaryl or C2-C14heterocycloalkyl of R2 are optionally further substituted with a CN group;
each R4 is independently selected from H, C1-C8 alkyl, -L1R5, -L1R8, C2-C13heteroaryl, C6-C14aryl, and C3-C8cycloalkyl, wherein the C1-C8alkyl, C2-C13heteroaryl and C3-C8cycloalkyl are optionally substituted with 1 to 3 substituents independently selected from halogen, deuterium, —CD3, —S(O)2R9, —CN, C1-C8alkyl, —OR9, —N(R9)2 and —(CH2)pOR9;
L1 is a bond, C1-C8alkylene, —O(CH2)p—, —C(O)—, —N(R9)—, (CH2)pC(O)—, or —C(O)(CH2)p0(CH2)p—;
Y1 is C6-C14arylene, C2-C13heteroarylene or C2-C14heterocycloalkylene each of which is optionally substituted with 1 to 3 substituents independently selected from halogen, C1-C8alkyl, —CN, —C(O)N(R4)2, —C(O)R9, —OR9, —C(O)OR9, —N(R4)2, —S(O)2R9, —S(O)2N(R4)2, —NR4S(O)2R4, hydroxyl-C1-C8alkyl, and halo-substituted C1-C8alkyl;
R5 is C6-C14aryl, C2-C13heteroaryl, —N(R9)2, —(CH2)pOR9 or —OR9;
R6 is C6-C14aryl, C2-C13heteroaryl or C3-C8cycloalkyl, wherein the C3-C8cycloalkyl, C6-C14aryl and C2-C13heteroaryl of R6 are optionally substituted with 1 to 3 substituents independently selected from halogen, —CN, —OR9, —(CH2)pOR9, -L1R8, -L1R5, C(O)R9, —C(O)OR9, —C(O)R8, OC(O)N(R4)2, —N(R9)2, —C(O)C(O)OR9, —(CH2)pN(R9)2, —N(R4)2, —C(O)N(R4)2, —N(R4)C(O)R4, —N(R4)C(O)OR4, —(CH2)pS(O)2R9, —S(O)2R9, —S(O)2N(R4)2, —NR4S(O)2R4, —NR4S(O)2R9, C1-C8alkyl, C2-C8alkene, hydroxyl-substituted C1-C8alkyl, and halo-substituted C1-C8alkyl;
or R6 is a C2-C14heterocycloalkyl substituted with 1 to 3 substituents independently selected from halogen, ═O, —CN, —OR9, —(CH2)pOR9, -L1R8, -L1R5, —C(O)R9, —C(O)OR9, —C(O)R8, OC(O)N(R4)2, —N(R9)2, —C(O)C(O)OR9, —(CH2)pN(R9)2, —N(R4)2, —C(O)N(R4)2, —N(R4)C(O)R4, —N(R4)C(O)OR4, —(CH2)pS(O)2R9, —S(O)2R9, —S(O)2N(R4)2, —NR4S(O)2R4, —NR4S(O)2R9, C1-C8alkyl, C2-C8alkene, hydroxyl-substituted C1-C8alkyl, and halo-substituted C1-C8alkyl;
R8 is H, —N(R9)2, —N(R4)2, —SR9, —CN, C1-C8alkyl, C3-C8cycloalkyl and C2-C14heterocycloalkyl,
wherein the C1-C8alkyl, C3-C8cycloalkyl and C2-C14heterocycloalkyl of R8 are optionally substituted with 1 to 3 substituents independently selected from halogen, C1-C6alkyl, —CN, —OR9, —(CH2)pOR9, —C(O)R9, —OC(O)R9, —C(O)OR9, —N(R9)2, —N(R4)2, —C(O)N(R4)2, —N(R4)C(O)R4, —N(R4)C(O)OR4, —S(O)2R9, —S(O)2N(R4)2, and —NR4S(O)2;
each R9 is independently selected from H, C3-C8cycloalkyl and C1-C8alkyl,
and
each p is independently 1, 2, 3, 4, 5 or 6.

16 more elements

A compound selected from:

6-(6-(3-(3-fluorophenyl)morpholino)imidazo[1,2-b]pyridazin-3-yl)indolin-2-one;
3-(6-((3S)-2-(3-fluorophenyl)-3-hydroxypyrrolidin-1-yl)imidazo[1,2-b]pyridazin-3-yl)benzonitrile;
5-(6-(2-(2,5-dimethylphenyl)pyrrolidin-1-yl)imidazo[1,2-b]pyridazin-3-yl)-2-fluorobenzonitrile;
(R)-4-(6-(2-(2,5-difluorophenyl)pyrrolidin-1-yl)imidazo[1,2-b]pyridazin-3-yl)benzonitrile;
4-(5-(6-(2-(3-fluorophenyl)piperidin-1-yl)imidazo[1,2-b]pyridazin-3-yl)pyridin-2-yl)morpholine;
4-(5-(6-(2-(3-fluorophenyl)pyrrolidin-1-yl)imidazo[1,2-b]pyridazin-3-yl)pyridin-2-yl)morpholine;
5-(6-(2-(3-fluorophenyl)pyrrolidin-1-yl)imidazo[1,2-b]pyridazin-3-yl)-N-methylpicolinamide;
4-(6-(2-(3-fluorophenyl)pyrrolidin-1-yl)imidazo[1,2-b]pyridazin-3-yl)benzonitrile;
5-(6-(2-(3-fluorophenyl)piperidin-1-yl)imidazo[1,2-b]pyridazin-3-yl)-N-methylpicolinamide;
(S)-4-(6-(2-(3-fluorophenyl)pyrrolidin-1-yl)imidazo[1,2-b]pyridazin-3-yl)benzonitrile;
(R)-4-(6-(2-(3-fluorophenyl)pyrrolidin-1-yl)imidazo[1,2-b]pyridazin-3-yl)benzonitrile;
4-(6-(2-(2,5-difluorophenyl)pyrrolidin-1-yl)imidazo[1,2-b]pyridazin-3-yl)benzonitrile;
4-(5-(6-(2-(2,5-difluorophenyl)pyrrolidin-1-yl)imidazo[1,2-b]pyridazin-3-yl)pyridin-2-yl)morpholine;
4-(6-(2-phenylazetidin-1-yl)imidazo[1,2-b]pyridazin-3-yl)benzonitrile;
(R)-4-(6-(2-(2,5-difluorophenyl)pyrrolidin-1-yl)imidazo[1,2-b]pyridazin-3-yl)benzonitrile;
(S)-4-(6-(2-(2,5-difluorophenyl)pyrrolidin-1-yl)imidazo[1,2-b]pyridazin-3-yl)benzonitrile;
4-(6-(2-(3-fluorophenyl)-2-methylpyrrolidin-1-yl)imidazo[1,2-b]pyridazin-3-yl)benzonitrile;
6-(6-(2-(3-fluorophenyl)pyrrolidin-1-yl)imidazo[1,2-b]pyridazin-3-yl)-3,4-dihydro-2H-benzo[e][1,3]oxazin-2-one;
6-(6-(2-(2,5-difluorophenyl)pyrrolidin-1-yl)imidazo[1,2-b]pyridazin-3-yl)-3,4-dihydro-2H-benzo[e][1,3]oxazin-2-one;
5-(6-(2-(3-fluorophenyl)pyrrolidin-1-yl)imidazo[1,2-b]pyridazin-3-yl)indolin-2-one;
6-(6-(2-(3-fluorophenyl)pyrrolidin-1-yl)imidazo[1,2-b]pyridazin-3-yl)indolin-2-one;
4-(6-(2-(2,5-difluorophenyl)-5-methylpyrrolidin-1-yl)imidazo[1,2-b]pyridazin-3-yl)benzonitrile;
4-(2-(4-(6-(2-(2,5-difluorophenyl)pyrrolidin-1-yl)imidazo[1,2-b]pyridazin-3-yl)-1H-pyrazol-1-yl)ethyl)morpholine;
N-(2-(4-(6-(2-(2,5-difluorophenyl)pyrrolidin-1-yl)imidazo[1,2-b]pyridazin-3-yl)-1H-pyrazol-1-yl)ethyl)acetamide;
(Z)-3-((1H-pyrrol-2-yl)methylene)-6-(6-(2-(3-fluorophenyl)pyrrolidin-1-yl)imidazo[1,2-b]pyridazin-3-yl)indolin-2-one;
5-(6-(2-(2,5-difluorophenyl)pyrrolidin-1-yl)imidazo[1,2-b]pyridazin-3-yl)-2-fluorobenzonitrile;
5-(6-(2-(2,5-difluorophenyl)pyrrolidin-1-yl)imidazo[1,2-b]pyridazin-3-yl)-2-morpholinobenzonitrile;
4-(6-(2-(2,5-difluorophenyl)pyrrolidin-1-yl)imidazo[1,2-b]pyridazin-3-yl)-2-fluorobenzonitrile;
5-(6-(2-(2,5-difluorophenyl)pyrrolidin-1-yl)imidazo[1,2-b]pyridazin-3-yl)-2-(dimethylamino)benzonitrile;
5-(6-(2-(2,5-difluorophenyl)pyrrolidin-1-yl)imidazo[1,2-b]pyridazin-3-yl)-2-(2-morpholinoethylamino)benzonitrile;
4-(6-(2-(2,5-difluorophenyl)pyrrolidin-1-yl)imidazo[1,2-b]pyridazin-3-yl)-2-(2-morpholinoethylamino)benzonitrile;
3-(6-(2-(2,5-difluorophenyl)pyrrolidin-1-yl)imidazo[1,2-b]pyridazin-3-yl)benzonitrile;
4-(6-(2-(2,5-difluorophenyl)pyrrolidin-1-yl)imidazo[1,2-b]pyridazin-3-yl)-2-(pyrrolidin-1-yl)benzonitrile;
4-(6-(2-(2,5-difluorophenyl)pyrrolidin-1-yl)imidazo[1,2-b]pyridazin-3-yl)-2-(2-(pyrrolidin-1-yl)ethoxy)benzonitrile;
5-(6-(2-(2,5-difluorophenyl)pyrrolidin-1-yl)imidazo[1,2-b]pyridazin-3-yl)nicotinonitrile;
6-(6-(2-(2,5-difluorophenyl)pyrrolidin-1-yl)imidazo[1,2-b]pyridazin-3-yl)picolinonitrile;
4-(4-(6-(2-(2,5-difluorophenyl)pyrrolidin-1-yl)imidazo[1,2-b]pyridazin-3-yl)thiazol-2-yl)morpholine;
4-(6-(2-(2,5-difluorophenyl)pyrrolidin-1-yl)imidazo[1,2-b]pyridazin-3-yl)-2-(3-morpholinopropylamino)benzonitrile;
4-(6-(2-(2,5-difluorophenyl)pyrrolidin-1-yl)imidazo[1,2-b]pyridazin-3-yl)-2-(1-methylpyrrolidin-3-yloxy)benzonitrile;
4-(6-(2-(2,5-difluorophenyl)pyrrolidin-1-yl)imidazo[1,2-b]pyridazin-3-yl)-2-((1-methylpyrrolidin-3-yl)methoxy)benzonitrile;
4-(6-(2-(2,5-difluorophenyl)pyrrolidin-1-yl)imidazo[1,2-b]pyridazin-3-yl)-2-(3-morpholinopropoxy)benzonitrile;
3-(5-(2-(3-fluorophenyl)pyrrolidin-1-yl)-3H-imidazo[4,5-b]pyridin-3-yl)benzonitrile;
4-(5-(2-(3-fluorophenyl)pyrrolidin-1-yl)-3H-imidazo[4,5-b]pyridin-3-yl)benzonitrile;
3-(5-(2-(2,5-difluorophenyl)thiazolidin-3-yl)-3H-imidazo[4,5-b]pyridin-3-yl)benzonitrile;
3-(5-(2-(2,5-difluorophenyl)thiazolidin-3-yl)-3H-imidazo[4,5-b]pyridin-3-yl)benzonitrile;
3-(3-(1H-imidazol-2-yl)phenyl)-5-(2-(2,5-difluorophenyl)pyrrolidin-1-yl)-3H-imidazo[4,5-b]pyridine;
3-(5-(2-(2,5-difluorophenyl)-4-oxothiazolidin-3-yl)-3H-imidazo[4,5-b]pyridin-3-yl)benzonitrile;
3-(5-(2-(2,5-difluorophenyl)pyrrolidin-1-yl)-3H-imidazo[4,5-b]pyridin-3-yl)benzonitrile;
4-(5-(2-(2,5-difluorophenyl)pyrrolidin-1-yl)-3H-imidazo[4,5-b]pyridin-3-yl)benzonitrile;
3-(6-(2-(3-fluorophenyl)-3-oxopyrazolidin-1-yl)imidazo[1,2-b]pyridazin-3-yl)benzonitrile;
2-(1,3-bis(dimethylamino)propan-2-yloxy)-4-(6-(2-(2,5-difluorophenyl)pyrrolidin-1-yl)imidazo[1,2-b]pyridazin-3-yl)benzonitrile;
4-(6-(2-(2,5-difluorophenyl)pyrrolidin-1-yl)imidazo[1,2-b]pyridazin-3-yl)-2-(1-(dimethylamino)propan-2-yloxy)benzonitrile;
4-(6-(2-(2,5-difluorophenyl)pyrrolidin-1-yl)imidazo[1,2-b]pyridazin-3-yl)-2-(2-(1-methylpyrrolidin-2-yl)ethoxy)benzonitrile;
4-(6-(2-(2,5-difluorophenyl)pyrrolidin-1-yl)imidazo[1,2-b]pyridazin-3-yl)-2-(3-(dimethylamino)-2-hydroxypropoxy)benzonitrile;
4-(6-(2-(2,5-difluorophenyl)pyrrolidin-1-yl)imidazo[1,2-b]pyridazin-3-yl)-2-((1-methylpyrrolidin-2-yl)methoxy)benzonitrile;
4-(6-(2-(3-fluorophenyl)piperidin-1-yl)imidazo[1,2-b]pyridazin-3-yl)benzonitrile;
3-(6-(2-(3-fluorophenyl)piperidin-1-yl)imidazo[1,2-b]pyridazin-3-yl)benzonitrile;
2-(2-(diethylamino)ethylamino)-4-(6-(2-(2,5-difluorophenyl)pyrrolidin-1-yl)imidazo[1,2-b]pyridazin-3-yl)benzonitrile;
7-(6-(2-(2,5-difluorophenyl)pyrrolidin-1-yl)imidazo[1,2-b]pyridazin-3-yl)-2-oxo-1,2-dihydroquinoline-3-carbonitrile;
5-(6-(2-(3-fluorophenyl)pyrrolidin-1-yl)imidazo[1,2-b]pyridazin-3-yl)-2-(2-morpholinoethylamino)benzonitrile;
5-(6-(2-(3-fluorophenyl)pyrrolidin-1-yl)imidazo[1,2-b]pyridazin-3-yl)-2-(2-(pyrrolidin-1-yl)ethoxy)benzonitrile;
5-(6-(2-(3-fluorophenyl)pyrrolidin-1-yl)imidazo[1,2-b]pyridazin-3-yl)-2-(2-(1-methylpyrrolidin-2-yl)ethoxy)benzonitrile;
4-(6-(2-(3-fluorophenyl)pyrrolidin-1-yl)imidazo[1,2-b]pyridazin-3-yl)-2-(2-(pyrrolidin-1-yl)ethoxy)benzonitrile;
4-(6-(2-(3-fluorophenyl)pyrrolidin-1-yl)imidazo[1,2-b]pyridazin-3-yl)-2-(2-morpholinoethoxy)benzonitrile;
(R)-3-(6-(2-(3-fluorophenyl)piperidin-1-yl)imidazo[1,2-b]pyridazin-3-yl)benzonitrile;
(S)-3-(6-(2-(3-fluorophenyl)piperidin-1-yl)imidazo[1,2-b]pyridazin-3-yl)benzonitrile;
4-(6-(3-(3-fluorophenyl)morpholino)imidazo[1,2-b]pyridazin-3-yl)benzonitrile;
(R)-4-(6-(2-(3-fluorophenyl)piperidin-1-yl)imidazo[1,2-b]pyridazin-3-yl)benzonitrile;
(S)-4-(6-(2-(3-fluorophenyl)piperidin-1-yl)imidazo[1,2-b]pyridazin-3-yl)benzonitrile;
6-(6-(2-(2,5-dimethylphenyl)pyrrolidin-1-yl)imidazo[1,2-b]pyridazin-3-yl)picolinic acid;
3-(6-((2R,4S)-3,3-difluoro-4-methyl-2-phenylpyrrolidin-1-yl)imidazo[1,2-b]pyridazin-3-yl)benzonitrile;
3-(6-(2-phenylpyrrolidin-1-yl)imidazo[1,2-b]pyridazin-3-yl)benzonitrile;
6-(6-(2-phenylpyrrolidin-1-yl)imidazo[1,2-b]pyridazin-3-yl)-3,4-dihydro-2H-benzo[e][1,3]oxazin-2-one;
4-(6-(2-(2,5-difluorophenyl)pyrrolidin-1-yl)imidazo[1,2-b]pyridazin-3-yl)-2-((R)-pyrrolidin-2-ylmethoxy)benzonitrile;
4-(6-(2-(2,5-difluorophenyl)pyrrolidin-1-yl)imidazo[1,2-b]pyridazin-3-yl)-2-((S)-pyrrolidin-2-ylmethoxy)benzonitrile
2-(4-(3-(dimethylamino)propyl)piperazin-1-yl)-5-(6-(2-(3-fluorophenyl)pyrrolidin-1-yl)imidazo[1,2-b]pyridazin-3-yl)benzonitrile;
5-(6-(2-(3-fluorophenyl)pyrrolidin-1-yl)imidazo[1,2-b]pyridazin-3-yl)-2-(2-(4-isopropylpiperazin-1-yl)ethoxy)benzonitrile;
5-(6-(2-(3-fluorophenyl)pyrrolidin-1-yl)imidazo[1,2-b]pyridazin-3-yl)-2-(2-(4-(2-hydroxyethyl)piperazin-1-yl)ethoxy)benzonitrile;
5-(6-(2-(3-fluorophenyl)pyrrolidin-1-yl)imidazo[1,2-b]pyridazin-3-yl)-2-(((R)-5-oxopyrrolidin-2-yl)methoxy)benzonitrile;
3-(6-((2R,4S)-3,3-difluoro-2-(3-fluorophenyl)-4-methylpyrrolidin-1-yl)imidazo[1,2-b]pyridazin-3-yl)benzonitrile;
6-(2-(3-fluorophenyl)pyrrolidin-1-yl)-3-(1H-indol-4-yl)imidazo[1,2-b]pyridazine;
6-(2-(3-fluorophenyl)pyrrolidin-1-yl)-3-(1-methyl-1H-indol-2-yl)imidazo[1,2-b]pyridazine;
6-(2-(3-fluorophenyl)pyrrolidin-1-yl)-3-(1H-indol-5-yl)imidazo[1,2-b]pyridazine;
4-(6-(2-(3-fluorophenyl)pyrrolidin-1-yl)imidazo[1,2-b]pyridazin-3-yl)-2-(piperidin-1-yl)thiazole;
6-(2-(3-fluorophenyl)pyrrolidin-1-yl)-3-(5-(pyrrolidin-1-yl)pyrazin-2-yl)imidazo[1,2-b]pyridazine;
3-(6-(2-(3-fluorophenyl)pyrrolidin-1-yl)imidazo[1,2-b]pyridazin-3-yl)benzonitrile;
tert-butyl 5-(6-(2-(3-fluorophenyl)pyrrolidin-1-yl)imidazo[1,2-b]pyridazin-3-yl)-2-methylphenylcarbamate;
6-(2-(3-fluorophenyl)pyrrolidin-1-yl)-3-(pyridin-2-yl)imidazo[1,2-b]pyridazine;
3-(6-chloropyrazin-2-yl)-6-(2-(3-fluorophenyl)pyrrolidin-1-yl)imidazo[1,2-b]pyridazine;
2-chloro-5-(6-(2-(3-fluorophenyl)pyrrolidin-1-yl)imidazo[1,2-b]pyridazin-3-yl)thiazole;
5-(6-(2-(3-fluorophenyl)pyrrolidin-1-yl)imidazo[1,2-b]pyridazin-3-yl)-N,N-dimethylpyrazin-2-amine;
6-(2-(3-fluorophenyl)pyrrolidin-1-yl)-3-(6-(piperazin-1-yl)pyridin-2-yl)imidazo[1,2-b]pyridazine;
4-(6-(6-(2-(3-fluorophenyl)pyrrolidin-1-yl)imidazo[1,2-b]pyridazin-3-yl)pyridin-2-yl)morpholine;
(S)-6-(6-(2-(2,5-difluorophenyl)pyrrolidin-1-yl)imidazo[1,2-b]pyridazin-3-yl)picolinonitrile;
(R)-6-(6-(2-(2,5-difluorophenyl)pyrrolidin-1-yl)imidazo[1,2-b]pyridazin-3-yl)picolinonitrile;
3-(6-(3-(3-fluorophenyl)morpholino)imidazo[1,2-b]pyridazin-3-yl)benzonitrile;
6-(2-(2,5-difluorophenyl)pyrrolidin-1-yl)-3-(1H-indol-4-yl)imidazo[1,2-b]pyridazine;
4-(6-(6-(2-(2,5-difluorophenyl)pyrrolidin-1-yl)imidazo[1,2-b]pyridazin-3-yl)pyridin-2-yl)morpholine;
6-(2-(2,5-difluorophenyl)pyrrolidin-1-yl)-3-(1H-indol-5-yl)imidazo[1,2-b]pyridazine;
(R)-4-(6-(3-(3-fluorophenyl)morpholino)imidazo[1,2-b]pyridazin-3-yl)benzonitrile;
(S)-4-(6-(3-(3-fluorophenyl)morpholino)imidazo[1,2-b]pyridazin-3-yl)benzonitrile;
6-(2-(3-fluorophenyl)pyrrolidin-1-yl)-3-(1H-indazol-5-yl)imidazo[1,2-b]pyridazine;
3-(5-fluoro-6-methylpyridin-2-yl)-6-(2-(3-fluorophenyl)pyrrolidin-1-yl)imidazo[1,2-b]pyridazine;
3-(3-fluorophenyl)-4-(3-(pyridin-2-yl)imidazo[1,2-b]pyridazin-6-yl)morpholine;
6-(6-(3-(3-fluorophenyl)morpholino)imidazo[1,2-b]pyridazin-3-yl)nicotinonitrile;
2-fluoro-5-(6-(3-(3-fluorophenyl)morpholino)imidazo[1,2-b]pyridazin-3-yl)benzonitrile;
6-(2-(3-fluorophenyl)pyrrolidin-1-yl)-3-(6-methoxypyridin-2-yl)imidazo[1,2-b]pyridazine;
6-(2-(3-fluorophenyl)pyrrolidin-1-yl)-3-(6-fluoropyridin-2-yl)imidazo[1,2-b]pyridazine;
5-(6-(2-(3-fluorophenyl)pyrrolidin-1-yl)imidazo[1,2-b]pyridazin-3-yl)-N-(2-hydroxyethyl)picolinamide;
5-(6-(2-(3-fluorophenyl)pyrrolidin-1-yl)imidazo[1,2-b]pyridazin-3-yl)picolinamide;
6-(2-(3-fluorophenyl)pyrrolidin-1-yl)-3-(1H-indazol-6-yl)imidazo[1,2-b]pyridazine;
6-(2-(2,5-difluorophenyl)pyrrolidin-1-yl)-3-(1H-indazol-6-yl)imidazo[1,2-b]pyridazine;
6-(2-(3-fluorophenyl)pyrrolidin-1-yl)-3-(6-(piperazin-1-yl)pyridin-3-yl)imidazo[1,2-b]pyridazine;
2-(6-(6-(2-(3-fluorophenyl)pyrrolidin-1-yl)imidazo[1,2-b]pyridazin-3-yl)pyridin-2-ylamino)ethanol;
6-(2-(2,5-difluorophenyl)pyrrolidin-1-yl)-3-(6-fluoropyridin-2-yl)imidazo[1,2-b]pyridazine;
7-(6-(2-(3-fluorophenyl)pyrrolidin-1-yl)imidazo[1,2-b]pyridazin-3-yl)-2-oxo-1,2-dihydroquinoline-3-carbonitrile;
4-(6-(2-(3-fluorophenyl)pyrrolidin-1-yl)imidazo[1,2-b]pyridazin-3-yl)-2-(piperazin-1-ylmethyl)benzonitrile;
N1,N1-diethyl-N2-(6-(6-(2-(3-fluorophenyl)pyrrolidin-1-yl)imidazo[1,2-b]pyridazin-3-yl)pyridin-2-yl)ethane-1,2-diamine;
(2S)-3-(6-(6-(2-(3-fluorophenyl)pyrrolidin-1-yl)imidazo[1,2-b]pyridazin-3-yl)pyridin-2-ylamino)propane-1,2-diol;
6-(2-(2,5-difluorophenyl)pyrrolidin-1-yl)-3-(6-(piperazin-1-yl)pyridin-3-yl)imidazo[1,2-b]pyridazine;
6-(2-(2,5-difluorophenyl)pyrrolidin-1-yl)-3-(6-(piperazin-1-yl)pyridin-2-yl)imidazo[1,2-b]pyridazine;
3-(3-fluorophenyl)-4-(3-(5-(morpholinomethyl)pyridin-2-yl)imidazo[1,2-b]pyridazin-6-yl)morpholine;
4-((6-(6-(2-(3-fluorophenyl)pyrrolidin-1-yl)imidazo[1,2-b]pyridazin-3-yl)pyridin-3-yl)methyl)morpholine;
4-(6-(3-(3-fluorophenyl)morpholino)imidazo[1,2-b]pyridazin-3-yl)-2-((4-methylpiperazin-1-yl)methyl)benzonitrile;
3-(3-fluorophenyl)-4-(3-(6-fluoropyridin-2-yl)imidazo[1,2-b]pyridazin-6-yl)morpholine;
(5-(6-(2-(3-fluorophenyl)pyrrolidin-1-yl)imidazo[1,2-b]pyridazin-3-yl)pyridin-2-yl)(4-hydroxypiperidin-1-yl)methanone;
3-(3-fluorophenyl)-4-(3-(6-morpholinopyridin-2-yl)imidazo[1,2-b]pyridazin-6-yl)morpholine;
3-(3-fluorophenyl)-4-(3-(6-(piperazin-1-yl)pyridin-2-yl)imidazo[1,2-b]pyridazin-6-yl)morpholine;
4-(6-(2-(2-fluorophenyl)pyrrolidin-1-yl)imidazo[1,2-b]pyridazin-3-yl)benzonitrile;
3-(6-(2-(2-fluorophenyl)pyrrolidin-1-yl)imidazo[1,2-b]pyridazin-3-yl)benzonitrile;
4-(4-(6-(2-(2-fluorophenyl)pyrrolidin-1-yl)imidazo[1,2-b]pyridazin-3-yl)thiazol-2-yl)morpholine;
N-(5-(6-(2-(3-fluorophenyl)pyrrolidin-1-yl)imidazo[1,2-b]pyridazin-3-yl)pyrazin-2-yl)cyclopropanecarboxamide;
4-(6-(2-(3-fluorophenyl)pyrrolidin-1-yl)imidazo[1,2-b]pyridazin-3-yl)-2-((4-methylpiperazin-1-yl)methyl)benzonitrile;
5-(6-(2-(3-fluorophenyl)pyrrolidin-1-yl)imidazo[1,2-b]pyridazin-3-yl)-2-methoxythiazole;
4-(6-(2-(3-fluorophenyl)pyrrolidin-1-yl)imidazo[1,2-b]pyridazin-3-yl)thiazole-2-carboxylic acid;
(4-(6-(2-(3-fluorophenyl)pyrrolidin-1-yl)imidazo[1,2-b]pyridazin-3-yl)thiazol-2-yl)methanol;
6-(2-(3-fluorophenyl)pyrrolidin-1-yl)-3-(1-methyl-1H-imidazol-2-yl)imidazo[1,2-b]pyridazine;
4-(6-(2-(3-fluorophenyl)pyrrolidin-1-yl)imidazo[1,2-b]pyridazin-3-yl)-2-(piperazin-1-ylmethyl)thiazole;
2,2′-(6-(6-(2-(3-fluorophenyl)pyrrolidin-1-yl)imidazo[1,2-b]pyridazin-3-yl)pyridin-2-ylazanediyl)diethanol;
4-(2-(6-(6-(2-(3-fluorophenyl)pyrrolidin-1-yl)imidazo[1,2-b]pyridazin-3-yl)pyridin-2-yloxy)ethyl)morpholine;
6-(2-(3-fluorophenyl)pyrrolidin-1-yl)-3-(6-(2-(pyrrolidin-1-yl)ethoxy)pyridin-2-yl)imidazo[1,2-b]pyridazine;
4-((6-(6-(2-(3-fluorophenyl)pyrrolidin-1-yl)imidazo[1,2-b]pyridazin-3-yl)pyridin-2-yl)methyl)morpholine;
4-((6-(6-(2-(3-fluorophenyl)pyrrolidin-1-yl)imidazo[1,2-b]pyridazin-3-yl)pyridin-2-yl)methyl)-2,6-dimethylmorpholine;
1-((6-(6-(2-(3-fluorophenyl)pyrrolidin-1-yl)imidazo[1,2-b]pyridazin-3-yl)pyridin-2-yl)methyl)pyrrolidin-3-ol;
4-(6-(2-(3-fluorophenyl)pyrrolidin-1-yl)imidazol[1,2-b]pyridazin-3-yl)-2-methoxythiazole;
6-(6-(2-(2,5-difluorophenyl)pyrrolidin-1-yl)imidazo[1,2-b]pyridazin-3-yl)nicotinonitrile;
5-(6-(3-(3-fluorophenyl)morpholino)imidazo[1,2-b]pyridazin-3-yl)-1-(piperidin-4-yl)-1H-benzo[d]imidazol-2(3H)-one;
(6-(6-(2-(3-fluorophenyl)pyrrolidin-1-yl)imidazo[1,2-b]pyridazin-3-yl)pyridin-2-yl)methanol;
6-(6-(2-(3-fluorophenyl)pyrrolidin-1-yl)imidazo[1,2-b]pyridazin-3-yl)picolinamide;
(R)-6-(2-(3-fluorophenyl)pyrrolidin-1-yl)-3-(6-fluoropyridin-2-yl)imidazo[1,2-b]pyridazine;
6-(6-(2-(3-fluorophenyl)pyrrolidin-1-yl)imidazo[1,2-b]pyridazin-3-yl)pyridin-2-ol;
6-(6-(2-(3-fluorophenyl)pyrrolidin-1-yl)imidazo[1,2-b]pyridazin-3-yl)picolinic acid;
2-fluoro-3-(6-(2-(3-fluorophenyl)pyrrolidin-1-yl)imidazo[1,2-b]pyridazin-3-yl)quinoline;
3-(6-(2-(3-fluorophenyl)pyrrolidin-1-yl)imidazo[1,2-b]pyridazin-3-yl)quinolin-2(1H)-one ;
5-(6-(2-(3-fluorophenyl)pyrrolidin-1-yl)imidazo[1,2-b]pyridazin-3-yl)quinoline;
6-(2-(3-fluorophenyl)pyrrolidin-1-yl)-3-(4-(methylsulfonyl)phenyl)imidazo[1,2-b]pyridazine;
(1-(6-(6-(2-(3-fluorophenyl)pyrrolidin-1-yl)imidazo[1,2-b]pyridazin-3-yl)pyridin-2-ylamino)cyclopentyl)methanol;
3-(6-(2-(3-fluorophenyl)pyrrolidin-1-yl)imidazo[1,2-b]pyridazin-3-yl)quinoline;
(6-(6-(2-(3-fluorophenyl)pyrrolidin-1-yl)imidazo[1,2-b]pyridazin-3-yl)pyridin-2-yl)(4-hydroxypiperidin-1-yl)methanone;
6-(2-(3-fluorophenyl)pyrrolidin-1-yl)-3-(2-fluoropyridin-4-yl)imidazo[1,2-b]pyridazine;
N1,N1-diethyl-N2-(6-(6-(2-(3-fluorophenyl)piperidin-1-yl)imidazo[1,2-b]pyridazin-3-yl)pyridin-2-yl)ethane-1,2-diamine;
4-(3-(6-(2,5-diazabicyclo [2.2.1]heptan-2-yl)pyridin-2-yl)imidazo[1,2-b]pyridazin-6-yl)-3-(3-fluorophenyl)morpholine;
6-(6-(3-(3-fluorophenyl)morpholino)imidazo[1,2-b]pyridazin-3-yl)-N-(2-(piperazin-1-yl)ethyl)pyridin-2-amine;
6-(2-(3-fluorophenyl)pyrrolidin-1-yl)-3-(6-(1-(methylsulfonyl)piperidin-4-yloxy)pyridin-2-yl)imidazo[1,2-b]pyridazine;
4-(6-(2-(2,5-difluorophenyl)pyrrolidin-1-yl)imidazo[1,2-a]pyridin-3-yl)-2-fluorobenzonitrile;
2-ethoxy-4-(6-(2-(3-fluorophenyl)pyrrolidin-1-yl)imidazo[1,2-a]pyridin-3-yl)thiazole;
5-(6-(2-(2,5-difluorophenyl)pyrrolidin-1-yl)imidazo[1,2-a]pyridin-3-yl)-2-fluorobenzonitrile;
4-(6-(2-(3-fluorophenyl)pyrrolidin-1-yl)imidazo[1,2-b]pyridazin-3-yl)picolinic acid;
5-(6-(2-(3-fluorophenyl)pyrrolidin-1-yl)imidazo[1,2-b]pyridazin-3-yl)picolinic acid;
4-(6-(6-(2-(pyridin-2-yl)pyrrolidin-1-yl)imidazo[1,2-b]pyridazin-3-yl)pyridin-2-yl)morpholine;
6-(6-(2-(3-fluorophenyl)piperidin-1-yl)imidazo[1,2-b]pyridazin-3-yl)-N-methylpyridin-2-amine;
6-(6-(2-(3-fluorophenyl)piperidin-1-yl)imidazo[1,2-b]pyridazin-3-yl)-N-isopropylpyridin-2-amine;
N-(6-(6-(2-(3-fluorophenyl)piperidin-1-yl)imidazo[1,2-b]pyridazin-3-yl)pyridin-2-yl)methanesulfonamide;
6-(6-(2-(3-fluorophenyl)piperidin-1-yl)imidazo[1,2-b]pyridazin-3-yl)-N,N-dimethylpyridin-2-amine;
6-(2-(3-fluorophenyl)piperidin-1-yl)-3-(6-(piperidin-4-yloxy)pyridin-2-yl)imidazo[1,2-b]pyridazine,
4-(6-(2-(2,5-difluorophenyl)pyrrolidin-1-yl)imidazo[1,2-a]pyridin-3-yl)-2-ethoxythiazole;
6-(6-(3-(3-fluorophenyl)morpholino)imidazo[1,2-b]pyridazin-3-yl)-N-(2-(piperazin-1-yl)ethyl)pyridin-2-amine;
(S)-6-(6-(3-(3-fluorophenyl)morpholino)imidazo[1,2-b]pyridazin-3-yl)indolin-2-one;
(R)-6-(6-(3-(3-fluorophenyl)morpholino)imidazo[1,2-b]pyridazin-3-yl)indolin-2-one;
3-(6-(1,3-dioxolan-2-yl)pyridin-2-yl)-6-(2-(3-fluorophenyl)pyrrolidin-1-yl)imidazo[1,2-b]pyridazine;
6-(6-(6-(2-(3-fluorophenyl)pyrrolidin-1-yl)imidazo[1,2-b]pyridazin-3-yl)pyridin-2-yl)pyrimidin-2(1H)-one;
2-(4-(6-(6-(2-(3-fluorophenyl)pyrrolidin-1-yl)imidazo[1,2-b]pyridazin-3-yl)pyridin-2-yl)pyrimidin-2-ylamino)ethanol;
3-{6-[2-(3-fluorophenyl)pyrrolidin-1-yl]imidazo[1,2-b]pyridazin-3-yl}-1,2-dihydroquinolin-2-one;
5-{6-[2-(3-fluorophenyl)pyrrolidin-1-yl]imidazo[1,2-b]pyridazin-3-yl}quinoline;
3-{6-[2-(3-fluorophenyl)pyrrolidin-1-yl]imidazo[1,2-b]pyridazin-3-yl}quinoline;
2-[(5-{6-[2-(3-fluorophenyl)pyrrolidin-1-yl]imidazo[1,2-b]pyridazin-3-yl}pyrimidin-2-yl)amino]ethan-1-ol;
5-{6-[2-(3-fluorophenyl)pyrrolidin-1-yl]imidazo[1,2-b]pyridazin-3-yl}-N-methylpyrimidin-2-amine;
5-{6-[2-(3-fluorophenyl)pyrrolidin-1-yl]imidazo[1,2-b]pyridazin-3-yl}-N,N-dimethylpyrimidin-2-amine;
2-chloro-5-{6-[2-(3-fluorophenyl)pyrrolidin-1-yl]imidazo[1,2-b]pyridazin-3-yl}pyrimidine;
tert-butyl 4-[(5-{6-[2-(3-fluorophenyl)pyrrolidin-1-yl]imidazo[1,2-b]pyridazin-3-yl}pyrimidin-2-yl)oxy]piperidine-1-carboxylate;
5-{6-[2-(3-fluorophenyl)pyrrolidin-1-yl]imidazo[1,2-b]pyridazin-3-yl}-2-(piperidin-4-yloxy)pyrimidine;
5-{6-[2-(3-fluorophenyl)pyrrolidin-1-yl]imidazo[1,2-b]pyridazin-3-yl}pyrimidine;
5-{6-[2-(3-fluorophenyl)pyrrolidin-1-yl]imidazo[1,2-b]pyridazin-3-yl}-1,2-dihydropyrimidine;
6-{6-[(2R)-2-(3-fluorophenyl)pyrrolidin-1-yl]imidazo[1,2-b]pyridazin-3-yl}-N-methyl-N-(piperidin-4-yl)pyridin-2-amine;
N-cyclobutyl-6-{6-[(2R)-2-(3-fluorophenyl)pyrrolidin-1-yl]imidazo[1,2-b]pyridazin-3-yl}pyridin-2-amine;
N-cyclopropyl-6-{6-[(2R)-2-(3-fluorophenyl)pyrrolidin-1-yl]imidazo[1,2-b]pyridazin-3-yl}pyridin-2-amine;
6-{6-[2-(3-fluorophenyl)piperidin-1-yl]imidazo[1,2-b]pyridazin-3-yl}-N,N-dimethylpyridin-2-amine;
3-{6-[(2R)-2-(3-fluorophenyl)pyrrolidin-1-yl]imidazo[1,2-b]pyridazin-3-yl}-1H-pyrrole;
6-{6-[3-(3-fluorophenyl)morpholin-4-yl]imidazo[1,2-b]pyridazin-3-yl}-N,N-dimethylpyridin-2-amine;
3-(3-fluorophenyl)-4-(3-(6-(piperidin-4-yloxy)pyridin-2-yl)imidazo[1,2-b]pyridazin-6-yl)morpholine;
2-{6-[2-(3-fluorophenyl)pyrrolidin-1-yl]imidazo[1,2-b]pyridazin-3-yl}-6-(piperidin-4-yloxy)pyridine;
6-(2-(3-fluorophenyl)pyrrolidin-1-yl)-3-(6-(piperidin-4-yloxy)pyridin-2-yl)imidazo[1,2-b]pyridazine;
4-(4-{6-[2-(3-fluorophenyl)pyrrolidin-1-yl]imidazo[1,2-b]pyridazin-3-yl}-1H-pyrazol-1-yl)piperidine;
2-fluoro-4-{6-[2-(3-fluorophenyl)pyrrolidin-1-yl]imidazo[1,2-b]pyridazin-3-yl}pyridine;
2-(3-fluorophenyl)-1-[3-(4-methanesulfonylphenyl)imidazo[1,2-b]pyridazin-6-yl]pyrrolidine;
6-{6-[2-(3-fluorophenyl)pyrrolidin-1-yl]imidazo[1,2-b]pyridazin-3-yl}pyridine-2-carboxylic acid;
6-{6-[2-(3-fluorophenyl)pyrrolidin-1-yl]imidazo[1,2-b]pyridazin-3-yl}pyridin-2-ol;
6-{6-[2-(3-fluorophenyl)pyrrolidin-1-yl]imidazo[1,2-b]pyridazin-3-yl}pyridine-2-carboxamide;
6-{6-[(2R)-2-(3-fluorophenyl)pyrrolidin-1-yl]imidazo[1,2-b]pyridazin-3-yl}pyridine-2-carboxamide;
6-{6-[(2S)-2-(3-fluorophenyl)pyrrolidin-1-yl]imidazo[1,2-b]pyridazin-3-yl}pyridine-2-carboxamide;
6-{6-[2-(3-fluorophenyl)pyrrolidin-1-yl]imidazo[1,2-b]pyridazin-3-yl}-N-methylpyridine-2-carboxamide;
(3R)-1-[(6-{6-[2-(3-fluorophenyl)pyrrolidin-1-yl]imidazo[1,2-b]pyridazin-3-yl}pyridin-2-yl)carbonyl]-N,N-dimethylpyrrolidin-3-amine;
1-[(6-{6-[2-(3-fluorophenyl)pyrrolidin-1-yl]imidazo[1,2-b]pyridazin-3-yl}pyridin-2-yl)carbonyl]piperidin-4-ol;
4-[(6-{6-[2-(3-fluorophenyl)pyrrolidin-1-yl]imidazo[1,2-b]pyridazin-3-yl}pyridin-2-yl)carbonyl]morpholine;
1-(6-{6-[(2R)-2-(3-fluorophenyl)pyrrolidin-1-yl]imidazo[1,2-b]pyridazin-3-yl}pyridin-2-yl)piperazine;
6-{6-[2-(3-fluorophenyl)pyrrolidin-1-yl]imidazo[1,2-b]pyridazin-3-yl}-N-[1-(propan-2-yl)piperidin-4-yl]pyridin-2-amine;
2-fluoro-6-{6-[(2S)-2-(3-fluorophenyl)pyrrolidin-1-yl]imidazo[1,2-b]pyridazin-3-yl}pyridine;
2-fluoro-6-{6-[(2R)-2-(3-fluorophenyl)pyrrolidin-1-yl]imidazo[1,2-b]pyridazin-3-yl}pyridine;
diethyl({2-[(6-{6-[2-(3-fluorophenyl)piperidin-1-yl]imidazo[1,2-b]pyridazin-3-yl}pyridin-2-yl)amino]ethyl})amine;
6-{6-[2-(3-fluorophenyl)piperidin-1-yl]imidazo[1,2-b]pyridazin-3-yl}-N-methylpyridin-2-amine;
6-{6-[2-(3-fluorophenyl)piperidin-1-yl]imidazo[1,2-b]pyridazin-3-yl}-N-(propan-2-yl)pyridin-2-amine;
N-(6-{6-[2-(3-fluorophenyl)piperidin-1-yl]imidazo[1,2-b]pyridazin-3-yl}pyridin-2-yl)methanesulfonamide;
2-{6-[2-(3-fluorophenyl)piperidin-1-yl]imidazo[1,2-b]pyridazin-3-yl}-6-(piperidin-4-yloxy)pyridine;
1-{6-[2-(3-fluorophenyl)pyrrolidin-1-yl]imidazo[1,2-b]pyridazin-3-yl}-1H-pyrazole;
2-{6-[2-(3-fluorophenyl)pyrrolidin-1-yl]imidazo[1,2-b]pyridazin-3-yl}-6-(piperazin-1-yl)pyrazine;
6-{6-[2-(3-fluorophenyl)pyrrolidin-1-yl]imidazo[1,2-b]pyridazin-3-yl}-2,3-dihydro-1H-indol-2-one;
6-{6-[3-(3-fluorophenyl)morpholin-4-yl]imidazo[1,2-b]pyridazin-3-yl}-2,3-dihydro-1H-indol-2-one;
3-(3-fluorophenyl)-4-{3-[6-(piperazin-1-yl)pyridin-2-yl]imidazo[1,2-b]pyridazin-6-yl}morpholine, and
(3S)-4-[3-(6-fluoropyridin-2-yl)imidazo[1,2-b]pyridazin-6-yl]-3-phenylmorpholine.

226 more elements

Dependencies are inferred from the claim text.

Facts

Application: 12/992,027Filed 7 May 2009 · us provisional application
Priority: 13 May 2008
Published: US 2011/0166133 A17 Jul 2011
Granted: 13 Aug 2013
Term ends: Not estimatedThe source records don’t support an estimate.

Classification33 codes

C07D 471/04
In which the condensed system contains two hetero rings: ortho-condensed systems
A61P 1/04
Drugs for disorders of the alimentary tract or the digestive system: for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of…
A61P 1/16
Drugs for disorders of the alimentary tract or the digestive system: for liver or gallbladder disorders, e.g. hepatoprotective agents,…
A61P 3/00
Drugs for disorders of the metabolism

Family

Application61/052,879Us provisional application · filed 13 May 2008
Application61/152,872Us provisional application · filed 16 Feb 2009
US 2011/0166133 A1Pre-grant publication · published 7 Jul 2011
US 8,507,488 B2This patent

From the US filing history. Foreign family members aren’t listed.

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Abstract

A compound of Formula (I), or a pharmaceutically acceptable salt thereof:

wherein:
X1 and X2 are N, and X3 and X4 are C;
wherein k is 1, 2 or 3;
each R3 is independently selected from halogen, C1-C8alkyl, C6-C14aryl, and C2-C13heteroaryl,
wherein the C1-C8alkyl, C6-C14aryl, and C2-C13heteroaryl of R3 are optionally substituted with 1 to 3 substituents independently selected from halogen, hydroxyl, cyano, —OR9, C1-C8alkyl, hydroxyl-C1-C8alkyl, halo-substituted-C1-C8alkyl and C3-C8cycloalkyl;
R2 is C6-C14aryl, C2-C13heteroaryl or C2-C14heterocycloalkyl,
wherein the C6-C14aryl, C2-C13heteroaryl or C2-C14heterocycloalkyl of R2 are substituted with 1 substituents independently selected from —R6 and —Y1R6;
and the C6-C14aryl, C2-C13heteroaryl or C2-C14heterocycloalkyl of R2 are optionally further substituted with a CN group;
each R4 is independently selected from H, C1-C8 alkyl, -L1R5, -L1R8, C2-C13heteroaryl, C6-C14aryl, and C3-C8cycloalkyl, wherein the C1-C8alkyl, C2-C13heteroaryl and C3-C8cycloalkyl are optionally substituted with 1 to 3 substituents independently selected from halogen, deuterium, —CD3, —S(O)2R9, —CN, C1-C8alkyl, —OR9, —N(R9)2 and —(CH2)pOR9;
L1 is a bond, C1-C8alkylene, —O(CH2)p—, —C(O)—, —N(R9)—, (CH2)pC(O)—, or —C(O)(CH2)p0(CH2)p—;
Y1 is C6-C14arylene, C2-C13heteroarylene or C2-C14heterocycloalkylene each of which is optionally substituted with 1 to 3 substituents independently selected from halogen, C1-C8alkyl, —CN, —C(O)N(R4)2, —C(O)R9, —OR9, —C(O)OR9, —N(R4)2, —S(O)2R9, —S(O)2N(R4)2, —NR4S(O)2R4, hydroxyl-C1-C8alkyl, and halo-substituted C1-C8alkyl;
R5 is C6-C14aryl, C2-C13heteroaryl, —N(R9)2, —(CH2)pOR9 or —OR9;
R6 is C6-C14aryl, C2-C13heteroaryl or C3-C8cycloalkyl, wherein the C3-C8cycloalkyl, C6-C14aryl and C2-C13heteroaryl of R6 are optionally substituted with 1 to 3 substituents independently selected from halogen, —CN, —OR9, —(CH2)pOR9, -L1R8, -L1R5, C(O)R9, —C(O)OR9, —C(O)R8, OC(O)N(R4)2, —N(R9)2, —C(O)C(O)OR9, —(CH2)pN(R9)2, —N(R4)2, —C(O)N(R4)2, —N(R4)C(O)R4, —N(R4)C(O)OR4, —(CH2)pS(O)2R9, —S(O)2R9, —S(O)2N(R4)2, —NR4S(O)2R4, —NR4S(O)2R9, C1-C8alkyl, C2-C8alkene, hydroxyl-substituted C1-C8alkyl, and halo-substituted C1-C8alkyl;
or R6 is a C2-C14heterocycloalkyl substituted with 1 to 3 substituents independently selected from halogen, ═O, —CN, —OR9, —(CH2)pOR9, -L1R8, -L1R5, —C(O)R9, —C(O)OR9, —C(O)R8, OC(O)N(R4)2, —N(R9)2, —C(O)C(O)OR9, —(CH2)pN(R9)2, —N(R4)2, —C(O)N(R4)2, —N(R4)C(O)R4, —N(R4)C(O)OR4, —(CH2)pS(O)2R9, —S(O)2R9, —S(O)2N(R4)2, —NR4S(O)2R4, —NR4S(O)2R9, C1-C8alkyl, C2-C8alkene, hydroxyl-substituted C1-C8alkyl, and halo-substituted C1-C8alkyl;
R8 is H, —N(R9)2, —N(R4)2, —SR9, —CN, C1-C8alkyl, C3-C8cycloalkyl and C2-C14heterocycloalkyl,
wherein the C1-C8alkyl, C3-C8cycloalkyl and C2-C14heterocycloalkyl of R8 are optionally substituted with 1 to 3 substituents independently selected from halogen, C1-C6alkyl, —CN, —OR9, —(CH2)pOR9, —C(O)R9, —OC(O)R9, —C(O)OR9, —N(R9)2, —N(R4)2, —C(O)N(R4)2, —N(R4)C(O)R4, —N(R4)C(O)OR4, —S(O)2R9, —S(O)2N(R4)2, and —NR4S(O)2;
each R9 is independently selected from H, C3-C8cycloalkyl and C1-C8alkyl,
and
each p is independently 1, 2, 3, 4, 5 or 6.

16 more elements

Facts

Application

12/992,027Filed 7 May 2009 · us provisional application

Priority

13 May 2008

Published

US 2011/0166133 A17 Jul 2011

Granted

13 Aug 2013

Term ends

Not estimatedThe source records don’t support an estimate.

Classification33 codes

C07D 471/04
In which the condensed system contains two hetero rings: ortho-condensed systems
A61P 1/04
Drugs for disorders of the alimentary tract or the digestive system: for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of…
A61P 1/16
Drugs for disorders of the alimentary tract or the digestive system: for liver or gallbladder disorders, e.g. hepatoprotective agents,…
A61P 3/00
Drugs for disorders of the metabolism