US 8,912,220 B2Granted

Compounds and methods of use thereof

AssigneeGalenea Pharmaceuticals

InventorsAmy Elder, Geraldine Harriman, Silvana Leit, Jie Li, Howard Sard, Yiliang Zhang, Doug Wilson

Life of this patent

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Abstract

Indole compounds are disclosed. Also disclosed are methods for using the compounds to treat human and animal disease, pharmaceutical compositions of the compounds, and kits including the compounds.

Claims20

Dependent claims

A compound of formula (I):

wherein
R1a and R2a are each independently selected from H and optionally substituted C1-8 alkyl;
R3 is selected from H and optionally substituted C1-8 alkyl;
W is optionally substituted arylC2-C6alkyl, optionally substituted with —ORd, —NRdRd′, or —C(O)NRdRd′, optionally substituted arylheteroalkyl, optionally substituted heteroarylheteroalkyl, -alkyl-O—O0-2alkyl-aryl, -alkyl-O—C0-2alkyl-heteroaryl, —(CH2)2—O-phenyl, or is selected from the group:
A is optionally substituted C1-4 alkylene, wherein alkylene is optionally substituted with 1-3 substituents, each of which is independently selected from the group consisting of halogen, oxo, optionally substituted C1-6 alkyl, —S(O)0-2alkyl, —ORd—NRdRd′, aryl, heteroaryl, C3-C8 cycloalkyl and 4-8 membered heterocycle;
R4 is selected from optionally substituted C1-8 alkyl, optionally substituted C1-8 heteroalkyl, C3-8 cycloalkyl, and cycloalkylalkyl, wherein the alkyl and cycloalkyl are optionally substituted with 1-3 substituents, halo, alkyl, haloalkyl, heteroalkyl, —ORd, —NRdRd′;
each R6 is independently selected from halo, C1-8 alkyl, aryl, heteroaryl, heteroalkyl, C3-8 cycloalkyl, heterocyclyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl, heterocycloalkyl, —SH, —ORd, C1-8 haloalkoxy, C1-8 haloalkyl, —S(O)0-2 C1-8 alkyl, —S(O)0-2 aryl, —S(O)0-2 heteroaryl, —S(O)0-2 arylalkyl, —S(O)0-2 heteroarylalkyl, —S(O)0-2 cycloalkyl, —S(O)0-2 heterocycloalkyl, —S(O)0-2 heterocycloalkylalkyl, —S(O)0-2 cycloalkylalkyl, —OC(O)NRdRd′, —NRdC(O)NRd′Rd″, —NRdC(O)ORa, —NRdS(O)2alkyl, —NRdS(O)2aryl, —NRdS(O)2heteroaryl, —NRdS(O)2cycloalkyl, —NRdS(O)2heterocycloalkyl, —NRdS(O)2—C1-4alkyl-aryl, —NRdS(O)2-heteroarylalkyl, —NRdS(O)2-cycloalkylalkyl, —NRaS(O)2-heterocycloalkyl, —SO2NRdRd′, cyano, nitro, C1-6 haloalkyl, C1-6 haloalkoxy, —NRdRd′, —C1-4alkyl-NRdRd′, optionally substituted C1-6 alkyl, —NRdC(O)Ra, —C(O)NRdRd′, and —C(O)ORd;
wherein alkyl, aryl, heteroaryl, cycloalkyl and heterocyclyl are optionally substituted;
each Ra is independently selected from optionally substituted C1-8 alkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted C3-8 cycloalkyl, optionally substituted arylalkyl, optionally substituted heteroarylalkyl, optionally substituted cycloalkylalkyl and optionally substituted heterocycloalkyl;
Rd, Rd′, and Rd″ are each independently selected from H and Ra, or when taken together with the atom to which they are attached, two of Rd, Rd′ and Rd″ form a 4-8 membered heterocyclic moiety;
and
g is 1, 2 or 3.

9 more elements

A compound selected from the group consisting of:

2-(1-ethyl-6-fluoro-4-(4-fluorobenzyloxy)-1H-indol-3-yl)-N,N-dimethylethanamine,
2-(1-ethyl-6-fluoro-4-(4-methoxybenzyloxy)-1H-indol-3-yl)-N,N-dimethylethanamine,
2-(4-(4-chlorobenzyloxy)-1-ethyl-6-fluoro-1H-indol-3-yl)-N,N-dimethylethanamine,
2-(1-ethyl-6-fluoro-4-(4-(trifluoromethoxy)benzyloxy)-1H-indol-3-yl)-N,N-dimethylethanamine,
2-(1-ethyl-6-fluoro-4-(4-(trifluoromethyl)benzyloxy)-1H-indol-3-yl)-N,N-dimethylethanamine,
2-(1-ethyl-6-fluoro-4-(2-(trifluoromethyl)benzyloxy)-1H-indol-3-yl)-N,N-dimethylethanamine,
2-(1-ethyl-6-fluoro-4-(3-(trifluoromethyl)benzyloxy)-1H-indol-3-yl)-N,N-dimethylethanamine,
2-(3-(2-(dimethylamino)ethyl)-1-ethyl-7-fluoro-1H-indol-4-yloxy)aniline,
2-(1-ethyl-7-fluoro-4-(2-nitrophenoxy)-1H-indol-3-yl)-N,N-dimethylethanamine,
2-(1-ethyl-6-fluoro-4-(5-fluoro-2-methylbenzyloxy)-1H-indol-3-yl)-N,N-dimethylethanamine,
2-(1-ethyl-6-fluoro-4-(pyridin-4-ylmethoxy)-1H-indol-3-yl)-N,N-dimethylethanamine,
2-(1-ethyl-6-fluoro-4-(thiophen-3-ylmethoxy)-1H-indol-3-yl)-N,N-dimethylethanamine,
2-(5-fluoro-1-methyl-4-phenethoxy-1H-indol-3-yl)-N,N-dimethylethanamine,
2-(1-ethyl-6-fluoro-4-phenoxy-1H-indol-3-yl)-N,N-dimethylethanamine,
2-(4-(2-chlorobenzyloxy)-6-fluoro-1-methyl-1H-indol-3-yl)-N-methylethanamine,
2-(4-(4-chlorobenzyloxy)-6-fluoro-1-methyl-1H-indol-3-yl)-N-methylethanamine,
2-(4-(3-chlorobenzyloxy)-6-fluoro-1-methyl-1H-indol-3-yl)-N-methylethanamine,
2-(4-(3-chlorobenzyloxy)-5-fluoro-1-methyl-1H-indol-3-yl)-N-methylethanamine,
2-(4-(4-chlorobenzyloxy)-5-fluoro-1-methyl-1H-indol-3-yl)-N-methylethanamine,
2-(5-fluoro-1-methyl-4-(3-(trifluoromethyl)benzyloxy)-1H-indol-3-yl)-Nmethylethanamine,
2-(5-fluoro-1-methyl-4-(2-methylbenzyloxy)-1H-indol-3-yl)-N-methylethanamine,
2-(4-(2-chlorobenzyloxy)-5-fluoro-1-methyl-1H-indol-3-yl)-N-methylethanamine,
2-(5-fluoro-4-(2-fluorobenzyloxy)-1-methyl-1H-indol-3-yl)-N-methylethanamine,
2-(5-fluoro-4-(4-methoxyphenethoxy)-1-methyl-1H-indol-3-yl)-N-methylethanamine,
2-(5-fluoro-1-methyl-4-phenethoxy-1H-indol-3-yl)-N-methylethanamine,
2-(5-fluoro-1-methyl-4-(4-methylbenzyloxy)-1H-indol-3-yl)-N-methylethanamine,
2-(5-fluoro-4-(4-fluorophenethoxy)-1-methyl-1H-indol-3-yl)-N-methylethanamine,
2-(4-(4-chlorophenethoxy)-5-fluoro-1-methyl-1H-indol-3-yl)-N-methylethanamine,
2-(4-(biphenyl-2-ylmethoxy)-5-fluoro-1-methyl-1H-indol-3-yl)-N-methylethanamine,
2-(5-fluoro-1-methyl-4-(2-(trifluoromethyl)benzyloxy)-1H-indol-3-yl)-N-methylethanamine,
2-(5-fluoro-1-methyl-4-(1-phenylethoxy)-1H-indol-3-yl)-N-methylethanamine,
2-((3-(2-((2-cyanobenzyl)(methyl)amino)ethyl)-5-fluoro-1-methyl-1H-indol-4-yloxy)methyl)benzonitrile,
2-(5-fluoro-4-(5-fluoro-2-methylbenzyloxy)-1-methyl-1H-indol-3-yl)-N-methylethanamine,
2-(5-fluoro-1-methyl-4-(2-(trifluoromethoxy)benzyloxy)-1H-indol-3-yl)-N-methylethanamine,
2-(5-fluoro-4-(4-fluorobenzyloxy)-1-methyl-1H-indol-3-yl)-N-methylethanamine,
2-(5-fluoro-1-methyl-4-(naphthalen-1-ylmethoxy)-1H-indol-3-yl)-N-methylethanamine,
1-(2-chlorophenyl)-2-(5-fluoro-1-methyl-3-(2-(methylamino)ethyl)-1H-indol-4-yloxy)ethanol,
2-(5-fluoro-1-methyl-4-(4-(methylsulfonyl)benzyloxy)-1H-indol-3-yl)-N-methylethanamine,
2-(5-fluoro-4-(naphthalen-1-ylmethoxy)-1-propyl-1H-indol-3-yl)-N-methylethanamine,
2-(4-(4-chlorobenzyloxy)-5-fluoro-1-propyl-1H-indol-3-yl)-N-methylethanamine,
2-(5-fluoro-1-methyl-4-(quinolin-8-ylmethoxy)-1H-indol-3-yl)-N-methylethanamine,
2-(5-fluoro-1-methyl-4-(2-phenoxyethoxy)-1H-indol-3-yl)-N-methylethanamine,
2-(5-fluoro-4-(4-fluorobenzyloxy)-1-propyl-1H-indol-3-yl)-N-methylethanamine,
2-(5-fluoro-4-(4-methylbenzyloxy)-1-propyl-1H-indol-3-yl)-N-methylethanamine,
2-(5-fluoro-1-methyl-4-(2-methylphenethoxy)-1H-indol-3-yl)-N-methylethanamine,
2-(5-fluoro-4-(4-(methylsulfonyl)benzyloxy)-1-propyl-1H-indol-3-yl)-N-methylethanamine,
2-(4-(2-chlorophenethoxy)-5-fluoro-1-methyl-1H-indol-3-yl)-N-methylethanamine,
2-(4-(2,4-dichlorobenzyloxy)-5-fluoro-1-methyl-1H-indol-3-yl)-N-methylethanamine,
2-(4-(4-chlorobenzyloxy)-5-fluoro-1-propyl-1H-indol-3-yl)ethanamine
2-(4-(4-chloro-3-(trifluoromethoxy)benzyloxy)-5-fluoro-1-methyl-1H-indol-3-yl)-N-methylethanamine, and
2-(5-fluoro-1-methyl-4-(thiophen-2-ylmethoxy)-1H-indol-3-yl)-N,N-dimethylethanamine.

48 more elements

A compound of formula (VIII):

wherein
g is 1, 2 or 3;
R1a is selected from H, optionally substituted C1-8 alkyl, and optionally substituted aryl;
Q is selected from aryl, heteroaryl, arylalkyl, heterocycloalkyl, and heteroarylalkyl, wherein Q is optionally substituted with 1-3 substituents, each of which is independently selected from the group consisting of halogen, C3-8 cycloalkyl, —ORd, C1-8 haloalkoxy, —S(O)0-2 C1-8 alkyl, —S(O)0-2 aryl, —S(O)0-2 heteroaryl, —S(O)0-2 arylalkyl, —S(O)0-2 heteroarylalkyl, —S(O)0-2 cycloalkyl, —S(O)0-2 heterocycloalkyl, —S(O)0-2 heterocycloalkylalkyl, —S(O)0-2 cycloalkylalkyl, —OC(O)NRdRd′, —NRdC(O)NRd′Rd″, —NRdC(O)ORb, —NRdS(O)2alkyl, —NRdS(O)2aryl, —NRdS(O)2heteroaryl, —NRdS(O)2cycloalkyl, —NRdS(O)2heterocycloalkyl, —NRdS(O)2-arylalkyl, —NRdS(O)2-heteroarylalkyl, —NRdS(O)2-cycloalkylalkyl, —SO2NRdRd′, cyano, nitro, C1-6 haloalkyl, —NRdRd′, optionally substituted —C1-6 alkyl, —NRdC(O)Ra, —C(O)NRdRd′, and —C(O), wherein Re and Rf are each independently selected from H, C1-8 alkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted arylalkyl, optionally substituted heteroarylalkyl, optionally substituted cycloalkyl, optionally substituted heterocyclyl, optionally substituted cycloalkylalkyl, optionally substituted heterocycloalkyl or when taken together with the nitrogen atom to which they are attached, R1 and R2 form a 3-8 membered heterocyclic moiety or when taken together with the nitrogen atom to which they are attached R1 or R2 and A form an optionally substituted 4-8 membered heterocyclyl or heteroaryl moiety;
R3 is selected from H, optionally substituted C1-8 alkyl, optionally substituted C3-8 cycloalkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted heterocyclyl, halogen, and C(O)NRdRd′;
W2 is hydrogen, optionally substituted C1-8 alkyl, optionally substituted aryl, optionally substituted arylalkyl, optionally substituted heteroaryl, optionally substituted heterocyclyl, optionally substituted heteroarylalkyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocycloalkyl, or —C(O)NRdRd′;
A is optionally substituted C1-4 alkylene, wherein the C1-4 alkylene is optionally substituted with 1-3 substituents, each of which is independently selected from the group consisting of halogen, hydroxyl, optionally substituted C1-6 alkyl, C1-8 alkoxy, —SO2 alkyl, and —NRdRd′;
R4 is selected from optionally substituted C1-8 alkyl, optionally substituted C1-8 heteroalkyl, C2-8 alkenyl, C2-8 alkynyl, —S(O)2 alkyl, —S(O)2 heteroalkyl, —S(O)2 heteroaryl, —S(O)2 cycloalkyl, —S(O)2 heterocyclyl, —S(O)2 heterocycloalkyl, —S(O)2 arylalkyl, —S(O)2 heteroarylalkyl, —S(O)2 cycloalkyalkyl, formyl, —ORd, —NRdRd′, —C(O)ORa, —C(O)NRdRd′, —S(O)2NRdRd′, C3-8 cycloalkyl, heterocyclyl, cycloalkylalkyl, heteocyclylalkyl, aryl, heteroaryl, arylalkyl, and heteroarylalkyl, wherein the alkyl, cycloalkyl and heterocyclyl are optionally substituted with 1-3 substituents, halo, alkyl, haloalkyl, heteroalkyl, —ORd, —NRdRd′, and wherein aryl and herteroaryl are optionally substituted with 1-3 substituents, each of which is independently selected from the group consisting of halogen, alkyl, heteroalkyl, cycloalkyl, heterocyclyl, —ORd, —SH, C1-8 haloalkoxy, —S(O)0-2 C1-8 alkyl, —S(O)0-2 aryl, —S(O)0-2 heteroaryl, —S(O)0-2-arylalkyl, —S(O)0-2-heteroarylalkyl, —OC(O)NRdRd′, —NRdC(O)NRd′Rd″, —NRdC(O)ORb, —ORd, —NRdS(O)2alkyl, —NRdS(O)2aryl, —NRdS(O)2heteroaryl, —NRdS(O)2cycloalkyl, —NRdS(O)2heterocycloalkyl, —NRdS(O)2-arylalkyl, —NRdS(O)2-heteroarylalkyl, —NRdS(O)2-cycloalkylalkyl, —NRdS(O)2-heterocycloalkyl, —SO2NRdRd′, optionally substituted —C1alkyl-C(O)NReRf, —C1alkyl-O-aryl, —C1alkyl-O-heteroaryl, —C1alkyl-heterocyclyl, —C1alkyl-cycloalkyl, cyano, nitro, C1-6 haloalkyl, C1-6 haloalkoxy, —NRdRd′, optionally substituted C1-6 alkyl, —NRdC(O)Ra, —C(O)NRdRd′, and —C(O)ORd;
each R6 is independently selected from halo, C1-8 alkyl, aryl, heteroaryl, heteroalkyl, C3-8 cycloalkyl, heterocyclyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl, heterocycloalkyl, —SH, —ORd, C1-8 haloalkoxy, C1-8 haloalkyl, —S(O)0-2 C1-8 alkyl, —S(O)0-2 aryl, —S(O)0-2 heteroaryl, —S(O)0-2 arylalkyl, —S(O)0-2 heteroarylalkyl, —S(O)0-2 cycloalkyl, —S(O)0-2 heterocycloalkyl, —S(O)0-2 heterocycloalkylalkyl, —S(O)0-2 cycloalkylalkyl, —OC(O)NRdRd′, —NRdC(O)NRd′Rd″, —NRdC(O)ORa, —NRdS(O)2alkyl, —NRdS(O)2aryl, —NRdS(O)2heteroaryl, —NRdS(O)2cycloalkyl, —NRdS(O)2heterocycloalkyl, —NRdS(O)2-arylalkyl, —NRdS(O)2-heteroarylalkyl, —NRdS(O)2-cycloalkylalkyl, —NRaS(O)2-heterocycloalkyl, —SO2NRdRd′, cyano, nitro, C1-6 haloalkyl, C1-6 haloalkoxy, —NRdRd′, —C1-4alkyl-NRdRd′, optionally substituted C1-6 alkyl, —NRdC(O)Ra, —C(O)NRdRd′, and —C(O)ORd;
wherein alkyl, aryl, heteroaryl, cycloalkyl and heterocyclyl are optionally substituted;
Ra and Rb are each independently selected from optionally substituted C1-8 alkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted C3-8 cycloalkyl, optionally substituted arylalkyl, optionally substituted heteroarylalkyl, optionally substituted cycloalkylalkyl and optionally substituted heterocycloalkyl;
and
Rd, Rd′, and Rd″ are each independently selected from H and Ra, or when taken together with the atom to which they are attached, two of Rd, Rd′ and Rd″ form a 4-8 membered heterocyclic moiety.

10 more elements

A compound selected from:

N-(2-(1-ethyl-7-fluoro-4-methoxy-1H-indol-3-yl)ethyl)aniline,
1-ethyl-7-fluoro-3-(2-(phenylamino)ethyl)-1H-indol-4-ol,
N-benzyl-2-(1-ethyl-7-fluoro-4-methoxy-1H-indol-3-yl)ethanamine,
3-(2-(benzylamino)ethyl)-1-ethyl-6-fluoro-1H-indol-4-ol,
2-(4-(benzyloxy)-1-ethyl-6-fluoro-1H-indol-3-yl)-N-(3-(trifluoromethyl)phenethyl)ethanamine,
1-ethyl-6-fluoro-3-(2-(3-(trifluoromethyl)phenethylamino)ethyl)-1H-indol-4-ol,
1-ethyl-6-fluoro-3-(2-(2-phenylpropylamino)ethyl)-1H-indol-4-ol,
N-benzyl-2-(4-(benzyloxy)-1-ethyl-6-fluoro-1H-indol-3-yl)ethanamine,
N-benzyl-2-(4-ethoxy-5-fluoro-1-methyl-1H-indol-3-yl)ethanamine,
N-(2-(4-ethoxy-5-fluoro-1-methyl-1H-indol-3-yl)ethyl)-2,3-dihydro-1H-inden-2-amine,
2-(4-(benzyloxy)-1-ethyl-6-fluoro-1H-indol-3-yl)-N-phenethylethanamine,
N-(2-chlorobenzyl)-2-(4-ethoxy-5-fluoro-1-methyl-1H-indol-3-yl)ethanamine,
N-(benzo[d][1,3]dioxol-5-ylmethyl)-2-(4-ethoxy-5-fluoro-1-methyl-1H-indol-3-yl)ethanamine,
N-(2-(4-ethoxy-5-fluoro-1-methyl-1H-indol-3-yl)ethyl)-2,3-dihydro-1H-inden-1-amine
1-ethyl-6-fluoro-3-(2-(phenethylamino)ethyl)-1H-indol-4-ol,
2-(4-ethoxy-5-fluoro-1-methyl-1H-indol-3-yl)-N-(3-methylbenzyl)ethanamine,
N-benzyl-2-(4-(benzyloxy)-1-ethyl-6-fluoro-1H-indol-3-yl)-N-methylethanamine,
2-(4-ethoxy-5-fluoro-1-methyl-1H-indol-3-yl)-N-(2-(trifluoromethyl)benzyl)ethanamine,
2-(4-ethoxy-5-fluoro-1-methyl-1H-indol-3-yl)-N-(3-(trifluoromethyl)benzyl)ethanamine,
2-(4-ethoxy-5-fluoro-1-methyl-1H-indol-3-yl)-N-phenethylethanamine,
2-(1-ethyl-7-fluoro-4-methoxy-1H-indol-3-yl)-N-phenethylethanamine,
2-(benzo[d][1,3]dioxol-5-yl)-N-(2-(4-ethoxy-5-fluoro-1-methyl-1H-indol-3-yl)ethyl)ethanamine,
N-benzyl-2-(1-ethyl-6-fluoro-4-methoxy-1H-indol-3-yl)ethanamine,
2-(4-ethoxy-5-fluoro-1-methyl-1H-indol-3-yl)-N-(2-(pyridin-2-yl)ethyl)ethanamine,
2-(4-ethoxy-5-fluoro-1-methyl-1H-indol-3-yl)-N-(thiophen-2-ylmethyl)ethanamine,
2-(5-fluoro-4-methoxy-1-methyl-1H-indol-3-yl)-N-(thiophen-2-ylmethyl)ethanamine,
N-benzyl-2-(5-fluoro-4-methoxy-1-methyl-1H-indol-3-yl)ethanamine,
2-(1-ethyl-6-fluoro-4-methoxy-1H-indol-3-yl)-N-(2-(1-ethyl-6-fluoro-4-methoxy-1H-indol-3-yl)ethyl)-N-methylethanamine,
2-(4-(benzyloxy)-1-ethyl-6-fluoro-1H-indol-3-yl)-N-(3-(trifluoromethyl)benzyl)ethanamine,
2-(4-(benzyloxy)-1-ethyl-6-fluoro-1H-indol-3-yl)-N-(3-chlorobenzyl)ethanamine,
2-(1-ethyl-7-fluoro-4-methoxy-1H-indol-3-yl)-N-(1-phenylethyl)ethanamine,
2-(1-ethyl-7-fluoro-4-methoxy-1H-indol-3-yl)-N-(2-methylbenzyl)ethanamine,
N-(2-chlorobenzyl)-2-(1-ethyl-7-fluoro-4-methoxy-1H-indol-3-yl)ethanamine,
N-(3,4-dimethoxybenzyl)-2-(5-fluoro-4-methoxy-1-methyl-1H-indol-3-yl)ethanamine,
3-(2-(benzhydrylamino)ethyl)-1-ethyl-6-fluoro-1H-indol-4-ol,
2-(2-(5-fluoro-4-methoxy-1-methyl-1H-indol-3-yl)ethylamino)-2-phenylethanol,
2-(5-fluoro-4-methoxy-1-methyl-1H-indol-3-yl)-N-(1-phenylethyl)ethanamine,
3-(2-(3-chlorobenzylamino)ethyl)-1-ethyl-6-fluoro-1H-indol-4-ol,
1-ethyl-6-fluoro-3-(2-(3-(trifluoromethyl)benzylamino)ethyl)-1H-indol-4-ol,
N-(2-(5-fluoro-4-methoxy-1-methyl-1H-indol-3-yl)ethyl)-4-phenylbutan-1-amine,
3-(2-(benzylamino)ethyl)-5-fluoro-1-methyl-1H-indol-4-ol,
(S)—N-(2-(5-fluoro-4-methoxy-1-methyl-1H-indol-3-yl)ethyl)-1,2,3,4-tetrahydronaphthalen-1-amine,
(S)—N-(2-(5-fluoro-4-methoxy-1-methyl-1H-indol-3-yl)ethyl)-1,2,3,4-tetrahydronaphthalen-1-amine,
N-(2-(5-fluoro-4-methoxy-1-methyl-1H-indol-3-yl)ethyl)-3-(4-methylpiperazin-1-yl)aniline,
5-fluoro-3-(2-((6-methylpyridin-2-yl)methylamino)ethyl)-1-propyl-1H-indol-4-ol, and
5-fluoro-1-methyl-3-(2-((6-methylpyridin-2-yl)methylamino)ethyl)-1H-indol-4-ol.

43 more elements

A compound of formula (I):

wherein
R1a and R2a are each independently selected from H and optionally substituted C1-8 alkyl;
R3 is selected from H and optionally substituted C1-8 alkyl;
W is
wherein:
when m is 1, then R5 is from F, Cl, Br, CF3, OH, —OCH3, —OCF3, and —S(O)0-2Ra;
and
when m is 2 or 3, then each R5 is independently selected from F, Cl, Br, CF3, methyl, OH, —OCH3, —OCF3, and —S(O)0-2Ra;
A is optionally substituted C1-4 alkylene, wherein alkylene is optionally substituted with 1-3 substituents, each of which is independently selected from the group consisting of halogen, oxo, optionally substituted C1-6 alkyl, —S(O)0-2alkyl, —ORd—NRdRd′, aryl, heteroaryl, C3-C8 cycloalkyl and 4-8 membered heterocycle;
R4 is selected from optionally substituted C1-8 alkyl, optionally substituted C1-8 heteroalkyl, C3-8 cycloalkyl, and cycloalkylalkyl, wherein the alkyl and cycloalkyl are optionally substituted with 1-3 substituents, halo, alkyl, haloalkyl, heteroalkyl, —ORd, —NRdRd′;
each R6 is independently selected from halo, C1-8 alkyl, aryl, heteroaryl, heteroalkyl, C3-8 cycloalkyl, heterocyclyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl, heterocycloalkyl, —SH, —ORd, C1-8 haloalkoxy, C1-8 haloalkyl, —S(O)0-2 C1-8 alkyl, —S(O)0-2 aryl, —S(O)0-2 heteroaryl, —S(O)0-2 arylalkyl, —S(O)0-2 heteroarylalkyl, —S(O)0-2 cycloalkyl, —S(O)0-2 heterocycloalkyl, —S(O)0-2 heterocycloalkylalkyl, —S(O)0-2 cycloalkylalkyl, —OC(O)NRdRd′, —NRdC(O)NRd′Rd″, —NRdC(O)ORa, —NRdS(O)2alkyl, —NRdS(O)2aryl, —NRdS(O)2heteroaryl, —NRdS(O)2cycloalkyl, —NRdS(O)2heterocycloalkyl, —NRdS(O)2—C1-4alkyl-aryl, —NRdS(O)2-heteroarylalkyl, —NRdS(O)2-cycloalkylalkyl, —NRaS(O)2-heterocycloalkyl, —SO2NRdRd′, cyano, nitro, C1-6 haloalkyl, C1-6 haloalkoxy, —NRdRd′, —C1-4alkyl-NRdRd′, optionally substituted C1-6 alkyl, —NRdC(O)Ra, —C(O)NRdRd′, and —C(O)ORd;
wherein alkyl, aryl, heteroaryl, cycloalkyl and heterocyclyl are optionally substituted;
each of R7 and R8 is independently H;
each Ra is independently selected from optionally substituted C1-8 alkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted C3-8 cycloalkyl, optionally substituted arylalkyl, optionally substituted heteroarylalkyl, optionally substituted cycloalkylalkyl and optionally substituted heterocyclo alkyl;
Rd, Rd′, and Rd″ are each independently selected from H and Ra, or when taken together with the atom to which they are attached, two of Rd, Rd′ and Rd″ form a 4-8 membered heterocyclic moiety;
and
g is 1, 2 or 3.

14 more elements

Dependencies are inferred from the claim text.

Facts

Application: 12/853,782Filed 10 Aug 2010 · us provisional application
Priority: 10 Aug 2009
Published: US 2011/0144090 A116 Jun 2011
Granted: 16 Dec 2014
Term ends: Not estimatedThe source records don’t support an estimate.

Classification25 codes

C07D 403/04
Containing two hetero rings: directly linked by a ring-member-to-ring-member bond
A61P 3/00
Drugs for disorders of the metabolism
A61P 3/04
Drugs for disorders of the metabolism: anorexiants; Antiobesity agents
A61P 3/10
For glucose homeostasis: for hyperglycaemia, e.g. antidiabetics

Family

Application61/232,772Us provisional application · filed 10 Aug 2009
US 2011/0144090 A1Pre-grant publication · published 16 Jun 2011
US 8,912,220 B2This patent

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

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Abstract

Indole compounds are disclosed. Also disclosed are methods for using the compounds to treat human and animal disease, pharmaceutical compositions of the compounds, and kits including the compounds.

A compound of formula (I):

wherein
R1a and R2a are each independently selected from H and optionally substituted C1-8 alkyl;
R3 is selected from H and optionally substituted C1-8 alkyl;
W is optionally substituted arylC2-C6alkyl, optionally substituted with —ORd, —NRdRd′, or —C(O)NRdRd′, optionally substituted arylheteroalkyl, optionally substituted heteroarylheteroalkyl, -alkyl-O—O0-2alkyl-aryl, -alkyl-O—C0-2alkyl-heteroaryl, —(CH2)2—O-phenyl, or is selected from the group:
A is optionally substituted C1-4 alkylene, wherein alkylene is optionally substituted with 1-3 substituents, each of which is independently selected from the group consisting of halogen, oxo, optionally substituted C1-6 alkyl, —S(O)0-2alkyl, —ORd—NRdRd′, aryl, heteroaryl, C3-C8 cycloalkyl and 4-8 membered heterocycle;
R4 is selected from optionally substituted C1-8 alkyl, optionally substituted C1-8 heteroalkyl, C3-8 cycloalkyl, and cycloalkylalkyl, wherein the alkyl and cycloalkyl are optionally substituted with 1-3 substituents, halo, alkyl, haloalkyl, heteroalkyl, —ORd, —NRdRd′;
each R6 is independently selected from halo, C1-8 alkyl, aryl, heteroaryl, heteroalkyl, C3-8 cycloalkyl, heterocyclyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl, heterocycloalkyl, —SH, —ORd, C1-8 haloalkoxy, C1-8 haloalkyl, —S(O)0-2 C1-8 alkyl, —S(O)0-2 aryl, —S(O)0-2 heteroaryl, —S(O)0-2 arylalkyl, —S(O)0-2 heteroarylalkyl, —S(O)0-2 cycloalkyl, —S(O)0-2 heterocycloalkyl, —S(O)0-2 heterocycloalkylalkyl, —S(O)0-2 cycloalkylalkyl, —OC(O)NRdRd′, —NRdC(O)NRd′Rd″, —NRdC(O)ORa, —NRdS(O)2alkyl, —NRdS(O)2aryl, —NRdS(O)2heteroaryl, —NRdS(O)2cycloalkyl, —NRdS(O)2heterocycloalkyl, —NRdS(O)2—C1-4alkyl-aryl, —NRdS(O)2-heteroarylalkyl, —NRdS(O)2-cycloalkylalkyl, —NRaS(O)2-heterocycloalkyl, —SO2NRdRd′, cyano, nitro, C1-6 haloalkyl, C1-6 haloalkoxy, —NRdRd′, —C1-4alkyl-NRdRd′, optionally substituted C1-6 alkyl, —NRdC(O)Ra, —C(O)NRdRd′, and —C(O)ORd;
wherein alkyl, aryl, heteroaryl, cycloalkyl and heterocyclyl are optionally substituted;
each Ra is independently selected from optionally substituted C1-8 alkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted C3-8 cycloalkyl, optionally substituted arylalkyl, optionally substituted heteroarylalkyl, optionally substituted cycloalkylalkyl and optionally substituted heterocycloalkyl;
Rd, Rd′, and Rd″ are each independently selected from H and Ra, or when taken together with the atom to which they are attached, two of Rd, Rd′ and Rd″ form a 4-8 membered heterocyclic moiety;
and
g is 1, 2 or 3.

9 more elements

Facts

Application

12/853,782Filed 10 Aug 2010 · us provisional application

Priority

10 Aug 2009

Published

US 2011/0144090 A116 Jun 2011

Granted

16 Dec 2014

Term ends

Not estimatedThe source records don’t support an estimate.

Classification25 codes

C07D 403/04
Containing two hetero rings: directly linked by a ring-member-to-ring-member bond
A61P 3/00
Drugs for disorders of the metabolism
A61P 3/04
Drugs for disorders of the metabolism: anorexiants; Antiobesity agents
A61P 3/10
For glucose homeostasis: for hyperglycaemia, e.g. antidiabetics