US 2018/0024144 A1 · INDOLE AND INDOLINE DERIVATIVES AND METHODS OF USE THEREOF

Abstract

The present application relates to indole and indoline derivatives of formula (I), (II), (III), (IV), (V), or (VI) wherein a, R1, R2, R3, R4, R5, U, V, W, X, Y, and Z are as defined in the specification. The present application also relates to compositions comprising such compounds, and methods of treating disease conditions using such compounds and compositions, and methods for identifying such compounds.

Claims3

Dependent claims

-27. (canceled)

A compound, or a pharmaceutically acceptable salt thereof, selected from the group consisting of:

2,11-dimethyl-5-[2-(6-methylpyridin-3-yl)ethyl]-5,6,7,8,9,10-hexahydro-7,10-epiminocyclohepta[b]indole;
5-[6-(4-iodophenyl)pyridazin-3-yl]-2,11-dimethyl-5,6,7,8,9,10-hexahydro-7,10-epiminocyclohepta[b]indole;
9-methyl-6-[2-(6-methylpyridin-3-yl)ethyl]-3,4,5,6-tetrahydro-1H-2,5-methanoazepino[4,3-b]indole;
2,8-dimethyl-5-[2-(6-methylpyridin-3-yl)ethyl]-2,3,4,5-tetrahydro-1H-1,4-methanopyrido[4,3-b]indole;
6,10-dimethyl-9-[2-(6-methylpyridin-3-yl)ethyl]-2,3,4,9-tetrahydro-1H-4,1-(epiminomethano)carbazole;
2,6-dimethyl-9-[2-(6-methylpyridin-3-yl)ethyl]-2,3,4,9-tetrahydro-1H-1,4-methano-3-carboline;
6,11-dimethyl-9-[2-(6-methylpyridin-3-yl)ethyl]-2,3,4,9-tetrahydro-1H-1,4-(epiminomethano)carbazole;
2,11-dimethyl-5-[2-(6-methylpyridin-3-yl)ethyl]-5,6,7,8,9,10-hexahydro-6,9-epiminocyclohepta[b]indole;
2,12-dimethyl-5-[2-(6-methylpyridin-3-yl)ethyl]-6,7,8,9,10,11-hexahydro-5H-6,10-epiminocycloocta[b]indole;
6,10-dimethyl-9-[2-(6-methylpyridin-3-yl)ethyl]-2,3,4,9-tetrahydro-1H-1,4-epiminocarbazole;
2,9-dimethyl-6-[2-(6-methylpyridin-3-yl)ethyl]-1,2,3,4,5,6-hexahydro-1,5-methanoazepino[4,3-b]indole;
2,9-dimethyl-6-[2-(6-methylpyridin-3-yl)ethyl]-1,2,3,4,5,6-hexahydro-1,4-methanoazepino[4,3-b]indole;
2,11-dimethyl-5-[2-(6-methylpyridin-3-yl)ethyl]-5,6,7,8,9,10-hexahydro-6,10-epiminocyclohepta[b]indole;
(5aS*,7S*,10R*,10aR*)-2,11-dimethyl-5-[2-(6-methylpyridin-3-yl)ethyl]-5,5a,6,7,8,9,10,10a-octahydro-7,10-epiminocyclohepta[b]indole;
(5aR*,7S*,10R*,10aS*)-2,11-dimethyl-5-[2-(6-methylpyridin-3-yl)ethyl]-5,5a,6,7,8,9,10,10a-octahydro-7,10-epiminocyclohepta[b]indole;
(5aS*,7S*,11R*,11aR*)-2,12-dimethyl-5-[2-(6-methylpyridin-3-yl)ethyl]-5a,6,7,8,9,10,11,11a-octahydro-5H-7,11-epiminocycloocta[b]indole;
(5aR*,7S*,11R*,11aS*)-2,12-dimethyl-5-[2-(6-methylpyridin-3-yl)ethyl]-5a,6,7,8,9,10,11,11a-octahydro-5H-7,11-epiminocycloocta[b]indole;
(5R*,5aS*,10bR*)-9-methyl-6-[2-(6-methylpyridin-3-yl)ethyl]-3,4,5,5a,6,10b-hexahydro-1H-2,5-methanoazepino[4,3-b]indole;
(5R*,5aR*,10bS*)-9-methyl-6-[2-(6-methylpyridin-3-yl)ethyl]-3,4,5,5a,6,10b-hexahydro-1H-2,5-methanoazepino[4,3-b]indole;
(1R*,4R*,4aS*,9bR*)-2,8-dimethyl-5-[2-(6-methylpyridin-3-yl)ethyl]-2,3,4,4a,5,9b-hexahydro-1H-1,4-methanopyrido[4,3-b]indole;
(1R*,4R*,4aR*,9bS*)-2,8-dimethyl-5-[2-(6-methylpyridin-3-yl)ethyl]-2,3,4,4a,5,9b-hexahydro-1H-1,4-methanopyrido[4,3-b]indole;
(1R*,4R*,4aR*,9aS*)-6,10-dimethyl-9-[2-(6-methylpyridin-3-yl)ethyl]-2,3,4,4a,9,9a-hexahydro-1H-4,1-(epiminomethano)carbazole;
(1R*,4R*,4aS*,9aR*)-6,10-dimethyl-9-[2-(6-methylpyridin-3-yl)ethyl]-2,3,4,4a,9,9a-hexahydro-1H-4,1-(epiminomethano)carbazole;
(1S*,4R*,4aS*,9aR*)-2,6-dimethyl-9-[2-(6-methylpyridin-3-yl)ethyl]-2,3,4,4a,9,9a-hexahydro-1H-1,4-methano-β-carboline;
(1S*,4R*,4aR*,9aS*)-2,6-dimethyl-9-[2-(6-methylpyridin-3-yl)ethyl]-2,3,4,4a,9,9a-hexahydro-1H-1,4-methano-β-carboline;
(1S*,4R*,4aS*,9aR*)-6,11-dimethyl-9-[2-(6-methylpyridin-3-yl)ethyl]-2,3,4,4a,9,9a-hexahydro-1H-1,4-(epiminomethano)carbazole;
(1S*,4R*,4aR*,9aS*)-6,11-dimethyl-9-[2-(6-methylpyridin-3-yl)ethyl]-2,3,4,4a,9,9a-hexahydro-1H-1,4-(epiminomethano)carbazole;
(5aR*,6S*,9R,10aS*)-2,11-dimethyl-5-[2-(6-methylpyridin-3-yl)ethyl]-5,5a,6,7,8,9,10,10a-octahydro-6,9-epiminocyclohepta[b]indole;
(5aS*,6S*,9R,10aR*)-2,11-dimethyl-5-[2-(6-methylpyridin-3-yl)ethyl]-5,5a,6,7,8,9,10,10a-octahydro-6,9-epiminocyclohepta[b]indole;
(5aR*,6S*,10R*,11aS*)-2,12-dimethyl-5-[2-(6-methylpyridin-3-yl)ethyl]-5a,6,7,8,9,10,11,11a-octahydro-5H-6,10-epiminocycloocta[b]indole;
(5aS*,6S*,10R*,11aR*)-2,12-dimethyl-5-[2-(6-methylpyridin-3-yl)ethyl]-5a,6,7,8,9,10,11,11a-octahydro-5H-6,10-epiminocycloocta[b]indole;
(1R*,4S*,4aR*,9aR*)-6,10-dimethyl-9-[2-(6-methylpyridin-3-yl)ethyl]-2,3,4,4a,9,9a-hexahydro-1H-1,4-epiminocarbazole;
(1R*,4S*,4aS*,9aS*)-6,10-dimethyl-9-[2-(6-methylpyridin-3-yl)ethyl]-2,3,4,4a,9,9a-hexahydro-1H-1,4-epiminocarbazole;
(1R*,5S*,5aS*,10bR*)-2,9-dimethyl-6-[2-(6-methylpyridin-3-yl)ethyl]-1,2,3,4,5,5a,6,10b-octahydro-1,5-methanoazepino[4,3-b]indole;
(1R*,5S*,5aR*,10bS*)-2,9-dimethyl-6-[2-(6-methylpyridin-3-yl)ethyl]-1,2,3,4,5,5a,6,10b-octahydro-1,5-methanoazepino[4,3-b]indole;
(1R*,4S*,5aS*,10bR*)-2,9-dimethyl-6-[2-(6-methylpyridin-3-yl)ethyl]-1,2,3,4,5,5a,6,10b-octahydro-1,4-methanoazepino[4,3-b]indole;
(1R*,4S*,5aR,10bS*)-2,9-dimethyl-6-[2-(6-methylpyridin-3-yl)ethyl]-1,2,3,4,5,5a,6,10b-octahydro-1,4-methanoazepino[4,3-b]indole;
(5aR*,6R*,10S*,10aR*)-2,11-dimethyl-5-[2-(6-methylpyridin-3-yl)ethyl]-5,5a,6,7,8,9,10,10a-octahydro-6,10-epiminocyclohepta[b]indole;
(5aS*,6R*,10 S*, 10aS*)-2,11-dimethyl-5-[2-(6-methylpyridin-3-yl)ethyl]-5,5a,6,7,8,9,10,10a-octahydro-6,10-epiminocyclohepta[b]indole;
1′,5-dimethyl-1-[2-(6-methylpyridin-3-yl)ethyl]-1,2-dihydrospiro[indole-3,3′-pyrrolidine];
1′,5-dimethyl-1-[2-(6-methylpyridin-3-yl)ethyl]-1,2-dihydrospiro[indole-3,3′-piperidine];
2-methyl-5-[2-(6-methylpyridin-3-yl)ethyl]-5,6,7,8,9,10-hexahydro-7,10-epiminocyclohepta[b]indole;
(7S,10R)-2-methyl-5-[2-(6-methylpyridin-3-yl)ethyl]-5,6,7,8,9,10-hexahydro-7,10-epiminocyclohepta[b]indole;
(7R,10S)-2-methyl-5-[2-(6-methylpyridin-3-yl)ethyl]-5,6,7,8,9,10-hexahydro-7,10-epiminocyclohepta[b]indole;
(7R,10S)-2,11-dimethyl-5-[2-(6-methylpyridin-3-yl)ethyl]-5,6,7,8,9,10-hexahydro-7,10-epiminocyclohepta[b]indole;
(7S,10R)-2,11-dimethyl-5-[2-(6-methylpyridin-3-yl)ethyl]-5,6,7,8,9,10-hexahydro-7,10-epiminocyclohepta[b]indole;
5-[2-(6-chloropyridin-3-yl)ethyl]-2,11-dimethyl-5,6,7,8,9,10-hexahydro-7,10-epiminocyclohepta[b]indole;
(7R,10S)-5-[2-(6-chloropyridin-3-yl)ethyl]-2,11-dimethyl-5,6,7,8,9,10-hexahydro-7,10-epiminocyclohepta[b]indole;
(7S,10R)-5-[2-(6-chloropyridin-3-yl)ethyl]-2,11-dimethyl-5,6,7,8,9,10-hexahydro-7,10-epiminocyclohepta[b]indole;
11-ethyl-2-methyl-5-[2-(6-methylpyridin-3-yl)ethyl]-5,6,7,8,9,10-hexahydro-7,10-epiminocyclohepta[b]indole;
11-(2-fluoroethyl)-2-methyl-5-[2-(6-methylpyridin-3-yl)ethyl]-5,6,7,8,9,10-hexahydro-7,10-epiminocyclohepta[b]indole;
2-methyl-5-[2-(6-methylpyridin-3-yl)ethyl]-11-(2,2,2-trifluoroethyl)-5,6,7,8,9,10-hexahydro-7,10-epiminocyclohepta[b]indole;
ethyl (7R,10S)-2-methyl-5-[2-(6-methylpyridin-3-yl)ethyl]-5,6,7,8,9,10-hexahydro-7,10-epiminocyclohepta[b]indole-11-carboxylate;
ethyl (7S,10R)-2-methyl-5-[2-(6-methylpyridin-3-yl)ethyl]-5,6,7,8,9,10-hexahydro-7,10-epiminocyclohepta[b]indole-11-carboxylate;
11-(4-chlorobenzoyl)-2-methyl-5-[2-(6-methylpyridin-3-yl)ethyl]-5,6,7,8,9,10-hexahydro-7,10-epiminocyclohepta[b]indole;
2-methyl-5-[2-(6-methylpyridin-3-yl)ethyl]-11-{[4-(trifluoromethyl)phenyl]sulfonyl})-5,6,7,8,9,10-hexahydro-7,10-epiminocyclohepta[b]indole;
(7R,10S)-2,11-dimethyl-5-[2-(2-methylpyridin-3-yl)ethyl]-5,6,7,8,9,10-hexahydro-7,10-epiminocyclohepta[b]indole;
2,11-dimethyl-5-[(Z)-2-pyridin-3-ylvinyl]-5,6,7,8,9,10-hexahydro-7,10-epiminocyclohepta[b]indole;
(7R,10S)-2,11-dimethyl-5-[(E)-2-pyridin-3-ylvinyl]-5,6,7,8,9,10-hexahydro-7,10-epiminocyclohepta[b]indole;
(7S,10R)-2,11-dimethyl-5-[(E)-2-pyridin-3-ylvinyl]-5,6,7,8,9,10-hexahydro-7,10-epiminocyclohepta[b]indole;
(7S,10R)-2, 1-dimethyl-5-[(E)-2-(6-methylpyridin-3-yl)vinyl]-5,6,7,8,9,10-hexahydro-7,10-epiminocyclohepta[b]indole;
(7S,10R)-2,11-dimethyl-5-[(Z)-2-(6-methylpyridin-3-yl)vinyl]-5,6,7,8,9,10-hexahydro-7,10-epiminocyclohepta[b]indole;
(7R,10S)-2-methyl-5-[(Z)-2-(6-methylpyridin-3-yl)vinyl]-5,6,7,8,9,10-hexahydro-7,10-epiminocyclohepta[b]indole;
(7S,10R)-2-methyl-5-[(Z)-2-(6-methylpyridin-3-yl)vinyl]-5,6,7,8,9,10-hexahydro-7,10-epiminocyclohepta[b]indole;
(7S,10R)-2,11-dimethyl-5-(2-pyri din-2-yl ethyl)-5,6,7,8,9,10-hexahydro-7,10-epiminocyclohepta[b]indole;
(7S,10R)-5-[2-(5-ethylpyridin-2-yl)ethyl]-2,11-dimethyl-5,6,7,8,9,10-hexahydro-7,10-epiminocyclohepta[b]indole;
(7S,10R)-2,11-dimethyl-5-(2-pyri din-4-yl ethyl)-5,6,7,8,9,10-hexahydro-7,10-epiminocyclohepta[b]indole;
2,11-dimethyl-5-(2-pyrimidin-5-ylethyl)-5,6,7,8,9,10-hexahydro-7,10-epiminocyclohepta[b]indole;
(7R,10S)-2, 1-dimethyl-5-[2-(2-methylpyrimidin-5-yl)ethyl]-5,6,7,8,9,10-hexahydro-7,10-epiminocyclohepta[b]indole;
(7S,10R)-2,11-dimethyl-5-[2-(2-methylpyrimidin-5-yl)ethyl]-5,6,7,8,9,10-hexahydro-7,10-epiminocyclohepta[b]indole;
(7R,10S)-2,11-dimethyl-5-[2-(6-methylpyridazin-3-yl)ethyl]-5,6,7,8,9,10-hexahydro-7,10-epiminocyclohepta[b]indole;
(7R,10S)-2, 1-dimethyl-5-[2-(5-methylpyrazin-2-yl)ethyl]-5,6,7,8,9,10-hexahydro-7,10-epiminocyclohepta[b]indole;
2,11-dimethyl-5-[2-(4-methyl-1,3-thiazol-5-yl)ethyl]-5,6,7,8,9,10-hexahydro-7,10-epiminocyclohepta[b]indole;
2,11-dimethyl-5-(2-phenylethyl)-5,6,7,8,9,10-hexahydro-7,10-epiminocyclohepta[b]indole;
2,11-dimethyl-5-[2-(2-methylphenyl)ethyl]-5,6,7,8,9,10-hexahydro-7,10-epiminocyclohepta[b]indole;
(7R,10S)-2,11-dimethyl-5-[2-(2-methylphenyl)ethyl]-5,6,7,8,9,10-hexahydro-7,10-epiminocyclohepta[b]indole;
(7S,10R)-2,11-dimethyl-5-[2-(2-methylphenyl)ethyl]-5,6,7,8,9,10-hexahydro-7,10-epiminocyclohepta[b]indole;
2,11-dimethyl-5-[2-(4-methylphenyl)ethyl]-5,6,7,8,9,10-hexahydro-7,10-epiminocyclohepta[b]indole;
5-[2-(4-fluorophenyl)ethyl]-2,11-dimethyl-5,6,7,8,9,10-hexahydro-7,10-epiminocyclohepta[b]indole;
5-[2-(3-fluorophenyl)ethyl]-2,11-dimethyl-5,6,7,8,9,10-hexahydro-7,10-epiminocyclohepta[b]indole;
5-[2-(2-fluorophenyl)ethyl]-2,11-dimethyl-5,6,7,8,9,10-hexahydro-7,10-epiminocyclohepta[b]indole;
(7R,10S)-5-[2-(4-chlorophenyl)ethyl]-2,11-dimethyl-5,6,7,8,9,10-hexahydro-7,10-epiminocyclohepta[b]indole;
(7S,10R)-5-[2-(4-chlorophenyl)ethyl]-2,11-dimethyl-5,6,7,8,9,10-hexahydro-7,10-epiminocyclohepta[b]indole;
(7S,10R)-5-[2-(2-chlorophenyl)ethyl]-2,11-dimethyl-5,6,7,8,9,10-hexahydro-7,10-epiminocyclohepta[b]indole;
5-[2-(4-bromophenyl)ethyl]-2,11-dimethyl-5,6,7,8,9,10-hexahydro-7,10-epiminocyclohepta[b]indole;
5-[2-(3-bromophenyl)ethyl]-2,11-dimethyl-5,6,7,8,9,10-hexahydro-7,10-epiminocyclohepta[b]indole;
2,11-dimethyl-5-{2-[4-(trifluoromethyl)phenyl]ethyl}-5,6,7,8,9,10-hexahydro-7,10-epiminocyclohepta[b]indole;
2,11-dimethyl-5-{2-[3-(trifluoromethyl)phenyl]ethyl}-5,6,7,8,9,10-hexahydro-7,10-epiminocyclohepta[b]indole;
(7R,10S)-2,11-dimethyl-5-{2-[3-(trifluoromethyl)phenyl]ethyl}-5,6,7,8,9,10-hexahydro-7,10-epiminocyclohepta[b]indole;
(7S,10R)-2,11-dimethyl-5-{2-[3-(trifluoromethyl)phenyl]ethyl}-5,6,7,8,9,10-hexahydro-7,10-epiminocyclohepta[b]indole;
2,11-dimethyl-5-{2-[2-(trifluoromethyl)phenyl]ethyl}-5,6,7,8,9,10-hexahydro-7,10-epiminocyclohepta[b]indole;
(7R,10S)-2,11-dimethyl-5-{2-[2-(trifluoromethyl)phenyl]ethyl}-5,6,7,8,9,10-hexahydro-7,10-epiminocyclohepta[b]indole;
(7S,10R)-2,11-dimethyl-5-{2-[2-(trifluoromethyl)phenyl]ethyl}-5,6,7,8,9,10-hexahydro-7,10-epiminocyclohepta[b]indole;
5-[2-(4-methoxyphenyl)ethyl]-2,11-dimethyl-5,6,7,8,9,10-hexahydro-7,10-epiminocyclohepta[b]indole;
(7R,10S)-2,11-dimethyl-5-[(E)-2-phenylvinyl]-5,6,7,8,9,10-hexahydro-7,10-epiminocyclohepta[b]indole;
2,11-dimethyl-5-[(E)-2-(4-methylphenyl)vinyl]-5,6,7,8,9,10-hexahydro-7,10-epiminocyclohepta[b]indole;
(7R,10S)-2,11-dimethyl-5-[(E)-2-(4-methylphenyl)vinyl]-5,6,7,8,9,10-hexahydro-7,10-epiminocyclohepta[b]indole;
2,11-dimethyl-5-[(Z)-2-(4-methylphenyl)vinyl]-5,6,7,8,9,10-hexahydro-7,10-epiminocyclohepta[b]indole;
(7R,10S)-2,11-dimethyl-5-[(Z)-2-(4-methylphenyl)vinyl]-5,6,7,8,9,10-hexahydro-7,10-epiminocyclohepta[b]indole;
(7R,10S)-5-[(E)-2-(2,4-dimethylphenyl)vinyl]-2,11-dimethyl-5,6,7,8,9,10-hexahydro-7,10-epiminocyclohepta[b]indole;
5-[(4-chlorophenyl)acetyl]-2,11-dimethyl-5,6,7,8,9,10-hexahydro-7,10-epiminocyclohepta[b]indole;
5-[2-(4-chlorophenyl)propyl]-2,11-dimethyl-5,6,7,8,9,10-hexahydro-7,10-epiminocyclohepta[b]indole;
5-(4-isopropenylphenyl)-2,11-dimethyl-5,6,7,8,9,10-hexahydro-7,10-epiminocyclohepta[b]indole;
2,11-dimethyl-5-(3-phenylpropyl)-5,6,7,8,9,10-hexahydro-7,10-epiminocyclohepta[b]indole;
5-[2-(4-fluorophenoxy)ethyl]-2,11-dimethyl-5,6,7,8,9,10-hexahydro-7,10-epiminocyclohepta[b]indole;
(7S,10R)-5-isoquinolin-7-yl-2,11-dimethyl-5,6,7,8,9,10-hexahydro-7,10-epiminocyclohepta[b]indole;
2,11-dimethyl-5-(phenylsulfonyl)-5,6,7,8,9,10-hexahydro-7,10-epiminocyclohepta[b]indole;
(7R,10S)-2,11-dimethyl-5-[(4-methylphenyl)sulfonyl]-5,6,7,8,9,10-hexahydro-7,10-epiminocyclohepta[b]indole;
(7S,10R)-2,11-dimethyl-5-[(4-methylphenyl)sulfonyl]-5,6,7,8,9,10-hexahydro-7,10-epiminocyclohepta[b]indole;
5-[(4-fluorophenyl)sulfonyl]-2,11-dimethyl-5,6,7,8,9,10-hexahydro-7,10-epiminocyclohepta[b]indole;
5-[(4-chlorophenyl)sulfonyl]-2,11-dimethyl-5,6,7,8,9,10-hexahydro-7,10-epiminocyclohepta[b]indole;
2,11-dimethyl-5-{[4-(trifluoromethyl)phenyl]sulfonyl}-5,6,7,8,9,10-hexahydro-7,10-epiminocyclohepta[b]indole;
5-[(4-methoxyphenyl)sulfonyl]-2,11-dimethyl-5,6,7,8,9,10-hexahydro-7,10-epiminocyclohepta[b]indole;
2,11-dimethyl-5-{[4-(trifluoromethoxy)phenyl]sulfonyl})-5,6,7,8,9,10-hexahydro-7,10-epiminocyclohepta[b]indole;
2,11-dimethyl-5-(pyridin-3-ylsulfonyl)-5,6,7,8,9,10-hexahydro-7,10-epiminocyclohepta[b]indole;
11-methyl-5-[2-(6-methylpyridin-3-yl)ethyl]-5,6,7,8,9,10-hexahydro-7,10-epiminocyclohepta[b]indole;
11-methyl-5-(2-phenylethyl)-5,6,7,8,9,10-hexahydro-7,10-epiminocyclohepta[b]indole;
11-methyl-5-[2-(2-methylphenyl)ethyl]-5,6,7,8,9,10-hexahydro-7,10-epiminocyclohepta[b]indole;
5-[2-(4-chlorophenyl)ethyl]-11-methyl-5,6,7,8,9,10-hexahydro-7,10-epiminocyclohepta[b]indole;
11-methyl-5-[2-(2-methyl-1,4,5,6-tetrahydropyrimidin-5-yl)ethyl]-5,6,7,8,9,10-hexahydro-7,10-epiminocyclohepta[b]indole;
11-methyl-5-{[4-(trifluoromethyl)phenyl]sulfonyl}-5,6,7,8,9,10-hexahydro-7,10-epiminocyclohepta[b]indole;
2-fluoro-11-methyl-5-[2-(4-methylphenyl)ethyl]-5,6,7,8,9,10-hexahydro-7,10-epiminocyclohepta[b]indole;
2-fluoro-5-[2-(4-fluorophenyl)ethyl]-11-methyl-5,6,7,8,9,10-hexahydro-7,10-epiminocyclohepta[b]indole;
2-fluoro-5-[2-(3-fluorophenyl)ethyl]-11-methyl-5,6,7,8,9,10-hexahydro-7,10-epiminocyclohepta[b]indole;
2-bromo-5-[2-(4-chlorophenyl)ethyl]-11-methyl-5,6,7,8,9,10-hexahydro-7,10-epiminocyclohepta[b]indole;
(7R,10S)-2-bromo-5-[2-(4-chlorophenyl)ethyl]-11-methyl-5,6,7,8,9,10-hexahydro-7,10-epiminocyclohepta[b]indole;
(7S,10R)-2-bromo-5-[2-(4-chlorophenyl)ethyl]-11-methyl-5,6,7,8,9,10-hexahydro-7,10-epiminocyclohepta[b]indole;
2-bromo-11-methyl-5-[(4-methylphenyl)sulfonyl]-5,6,7,8,9,10-hexahydro-7,10-epiminocyclohepta[b]indole;
2-methoxy-11-methyl-5-[2-(6-methylpyridin-3-yl)ethyl]-5, 6,7,8,9,10-hexahydro-7,10-epiminocyclohepta[b]indole;
(7R,10S)-5-[2-(4-chlorophenyl)ethyl]-2-methoxy-11-methyl-5,6,7,8,9,10-hexahydro-7,10-epiminocyclohepta[b]indole;
(7S,10R)-5-[2-(4-chlorophenyl)ethyl]-2-methoxy-11-methyl-5,6,7,8,9,10-hexahydro-7,10-epiminocyclohepta[b]indole;
(7R,10S)-2-methoxy-11-methyl-5-{2-[3-(trifluoromethyl)phenyl]ethyl}-5,6,7,8,9,10-hexahydro-7,10-epiminocyclohepta[b]indole;
(7S,10R)-2-methoxy-11-methyl-5-{2-[3-(trifluoromethyl)phenyl]ethyl}-5,6,7,8,9,10-hexahydro-7,10-epiminocyclohepta[b]indole;
5-[2-(4-chlorophenyl)ethyl]-4-methoxy-11-methyl-5,6,7,8,9,10-hexahydro-7,10-epiminocyclohepta[b]indole;
5-[2-(4-chlorophenyl)ethyl]-11-methyl-2-(trifluoromethoxy)-5,6,7,8,9,10-hexahydro-7,10-epiminocyclohepta[b]indole;
5-[2-(4-chlorophenyl)ethyl]-11-methyl-2-(trifluoromethyl)-5,6,7,8,9,10-hexahydro-7,10-epiminocyclohepta[b]indole;
2-isopropyl-11-methyl-5-[2-(6-methylpyridin-3-yl)ethyl]-5,6,7,8,9,10-hexahydro-7,10-epiminocyclohepta[b]indole;
(7R,10S)-5-[2-(4-chlorophenyl)ethyl]-2-isopropyl-11-methyl-5,6,7,8,9,10-hexahydro-7,10-epiminocyclohepta[b]indole;
(7S,10R)-5-[2-(4-chlorophenyl)ethyl]-2-isopropyl-11-methyl-5,6,7,8,9,10-hexahydro-7,10-epiminocyclohepta[b]indole;
2-cyclopropyl-11-methyl-5-[(4-methylphenyl)sulfonyl]-5,6,7,8,9,10-hexahydro-7,10-epiminocyclohepta[b]indole;
2-cyclopropyl-11-methyl-5-[2-(6-methylpyridin-3-yl)ethyl]-5,6,7,8,9,10-hexahydro-7,10-epiminocyclohepta[b]indole;
2-tert-butyl-11-methyl-5-[2-(6-methylpyridin-3-yl)ethyl]-5,6,7,8,9,10-hexahydro-7,10-epiminocyclohepta[b]indole;
2-tert-butyl-5-[2-(4-chlorophenyl)ethyl]-11-methyl-5,6,7,8,9,10-hexahydro-7,10-epiminocyclohepta[b]indole;
2-(4-chlorophenyl)-11-methyl-5-[2-(6-methylpyridin-3-yl)ethyl]-5,6,7,8,9,10-hexahydro-7,10-epiminocyclohepta[b]indole;
2-bromo-11-methyl-5-[2-(6-methylpyridin-3-yl)ethyl]-5,6,7,8,9,10-hexahydro-7,10-epiminocyclohepta[b]indole;
2-(4-chlorophenyl)-5-[2-(4-chlorophenyl)ethyl]-11-methyl-5,6,7,8,9,10-hexahydro-7,10-epiminocyclohepta[b]indole;
11-methyl-5-[2-(6-methylpyridin-3-yl)ethyl]-2-[3-(trifluoromethyl)phenyl]-5,6,7,8,9,10-hexahydro-7,10-epiminocyclohepta[b]indole;
5-[2-(4-chlorophenyl)ethyl]-11-methyl-2-[3-(trifluoromethyl)phenyl]-5,6,7,8,9,10-hexahydro-7,10-epiminocyclohepta[b]indole;
11-methyl-5-[2-(6-methylpyridin-3-yl)ethyl]-2-pyridin-3-yl-5,6,7,8,9,10-hexahydro-7,10-epiminocyclohepta[b]indole;
5-[2-(4-chlorophenyl)ethyl]-11-methyl-2-pyridin-3-yl-5,6,7,8,9,10-hexahydro-7,10-epiminocyclohepta[b]indole;
11-methyl-5-[2-(6-methylpyridin-3-yl)ethyl]-2-(1H-pyrazol-4-yl)-5,6,7,8,9,10-hexahydro-7,10-epiminocyclohepta[b]indole;
(5aS,7S,10R,10aR)-2,11-dimethyl-5-[2-(6-methylpyridin-3-yl)ethyl]-5,5a,6,7,8,9,10,10a-octahydro-7,10-epiminocyclohepta[b]indole;
2,12-dimethyl-5-[2-(6-methylpyridin-3-yl)ethyl]-6,7,8,9,10,11-hexahydro-5H-7,11-epiminocycloocta[b]indole;
(7R,11S)-2,12-dimethyl-5-[2-(6-methylpyridin-3-yl)ethyl]-6,7,8,9,10,11-hexahydro-5H-7,11-epiminocycloocta[b]indole;
(7S,11R)-2,12-dimethyl-5-[2-(6-methylpyridin-3-yl)ethyl]-6,7,8,9,10,11-hexahydro-5H-7,11-epiminocycloocta[b]indole;
5-[2-(6-chloropyridin-3-yl)ethyl]-2,12-dimethyl-6,7,8,9,10,11-hexahydro-5H-7,11-epiminocycloocta[b]indole;
(7R,11S)-2-methyl-5-[(Z)-2-(6-methylpyridin-3-yl)vinyl]-6,7,8,9,10,11-hexahydro-5H-7,11-epiminocycloocta[b]indole;
(7S,11R)-2-methyl-5-[(Z)-2-(6-methylpyridin-3-yl)vinyl]-6,7,8,9,10,11-hexahydro-5H-7,11-epiminocycloocta[b]indole;
(7R,11S)-2-methyl-5-[2-(6-methylpyridin-3-yl)ethyl]-6,7,8,9,10,11-hexahydro-5H-7,11-epiminocycloocta[b]indole;
(7S,11R)-2-methyl-5-[2-(6-methylpyridin-3-yl)ethyl]-6,7,8,9,10,11-hexahydro-5H-7,11-epiminocycloocta[b]indole;
2,12-dimethyl-5-[(E)-2-(6-methylpyridin-3-yl)vinyl]-6,7,8,9,10,11-hexahydro-5H-7,11-epiminocycloocta[b]indole;
(7R,11S)-2,12-dimethyl-5-[(Z)-2-(6-methylpyridin-3-yl)vinyl]-6,7,8,9,10,11-hexahydro-5H-7,11-epiminocycloocta[b]indole;
(7S,11R)-2,12-dimethyl-5-[(Z)-2-(6-methylpyridin-3-yl)vinyl]-6,7,8,9,10,11-hexahydro-5H-7,11-epiminocycloocta[b]indole;
(7R,11S)-2-methyl-5-[(E)-2-(6-methylpyridin-3-yl)vinyl]-6,7,8,9,10,11-hexahydro-5H-7,11-epiminocycloocta[b]indole;
(7S,11R)-2-methyl-5-[(E)-2-(6-methylpyridin-3-yl)vinyl]-6,7,8,9,10,11-hexahydro-5H-7,11-epiminocycloocta[b]indole;
(7R,11S)-2-methyl-5-[2-(2-methylphenyl)ethyl]-6,7,8,9,10,11-hexahydro-5H-7,11-epiminocycloocta[b]indole;
(7S,11R)-2-methyl-5-[2-(2-methylphenyl)ethyl]-6,7,8,9,10,11-hexahydro-5H-7,11-epiminocycloocta[b]indole;
(7R,11S)-5-[2-(2,5-dimethylphenyl)ethyl]-2-methyl-6,7,8,9,10,11-hexahydro-5H-7,11-epiminocycloocta[b]indole;
(7S,11R)-5-[2-(2,5-dimethylphenyl)ethyl]-2-methyl-6,7,8,9,10,11-hexahydro-5H-7,11-epiminocycloocta[b]indole;
(7R,11S)-5-[2-(4-chlorophenyl)ethyl]-2-methyl-6,7,8,9,10,11-hexahydro-5H-7,11-epiminocycloocta[b]indole;
(7S,11R)-5-[2-(4-chlorophenyl)ethyl]-2-methyl-6,7,8,9,10,11-hexahydro-5H-7,11-epiminocycloocta[b]indole;
(7R,11S)-2-methyl-5-{2-[3-(trifluoromethyl)phenyl]ethyl}-6,7,8,9,10,11-hexahydro-5H-7,11-epiminocycloocta[b]indole;
2-methyl-5-{(E)-2-[3-(trifluoromethyl)phenyl]vinyl}-6,7,8,9,10,11-hexahydro-5H-7,11-epiminocycloocta[b]indole;
(7S,11R)-2-methyl-5-{2-[3-(trifluoromethyl)phenyl]ethyl}-6,7,8,9,10,11-hexahydro-5H-7,11-epiminocycloocta[b]indole;
12-ethyl-2-methyl-5-{2-[3-(trifluoromethyl)phenyl]ethyl}-6,7,8,9,10,11-hexahydro-5H-7,11-epiminocycloocta[b]indole;
(7R,11S)-2-methyl-5-{(E)-2-[3-(trifluoromethyl)phenyl]vinyl}-6,7,8,9,10,11-hexahydro-5H-7,11-epiminocycloocta[b]indole;
(7S,11R)-2-methyl-5-{(E)-2-[3-(trifluoromethyl)phenyl]vinyl}-6,7,8,9,10,11-hexahydro-5H-7,11-epiminocycloocta[b]indole;
2-methyl-5-{(Z)-2-[3-(trifluoromethyl)phenyl]vinyl}-6,7,8,9,10,11-hexahydro-5H-7, 11-epiminocycloocta[b]indole;
5-[2-(6-methylpyridin-3-yl)ethyl]-2-(trifluoromethoxy)-6,7,8,9,10,11-hexahydro-5H-7,11-epiminocycloocta[b]indole;
5-[2-(2-methylphenyl)ethyl]-2-(trifluoromethoxy)-6,7,8,9,10,11-hexahydro-5H-7,11-epiminocycloocta[b]indole;
ethyl (9-methyl-1,3,4,5-tetrahydro-6H-2, 5-ethanoazepino[4,3-b]indol-6-yl)acetate;
N-(4-chlorophenyl)-2-(9-methyl-1,3,4,5-tetrahydro-6H-2, 5-ethanoazepino[4,3-b]indol-6-yl)acetamide;
2-(9-methyl-1,3,4,5-tetrahydro-6H-2,5-ethanoazepino[4,3-b]indol-6-yl)-N-[4-(trifluoromethoxy)phenyl]acetamide;
9-fluoro-6-[(2-methyl-1,3-thiazol-4-yl)methyl]-3,4,5,6-tetrahydro-1H-2, 5-ethanoazepino[4,3-b]indole;
9-fluoro-6-[(2-phenyl-1,3-oxazol-4-yl)methyl]-3,4,5,6-tetrahydro-1H-2,5-ethanoazepino[4,3-b]indole;
8-[(6-chloropyridin-3-yl)methyl]-11-fluoro-1,4,5,6,7, 8-hexahydro-2H-1,5:3,7-dimethanoazonino[5,4-b]indole;
5-[2-(6-chloropyridin-3-yl)ethyl]-2,11-dimethyl-5,6,7,8,9,10-hexahydro-6,10-epiminocyclohepta[b]indole;
(6R,10S)-5-[2-(6-chloropyridin-3-yl)ethyl]-2,11-dimethyl-5,6,7,8,9,10-hexahydro-6,10-epiminocyclohepta[b]indole;
(6S,10R)-5-[2-(6-chloropyridin-3-yl)ethyl]-2,11-dimethyl-5,6,7,8,9,10-hexahydro-6,10-epiminocyclohepta[b]indole;
10-methyl-7-[2-(6-methylpyridin-3-yl)ethyl]-1,3,4,5,6,7-hexahydro-2,6-methanoazocino[4,3-b]indole;
10-methyl-7-[2-(2-methylphenyl)ethyl]-1,3,4,5,6,7-hexahydro-2,6-methanoazocino[4,3-b]indole;
7-[2-(4-chlorophenyl)ethyl]-10-methyl-1,3,4,5,6,7-hexahydro-2,6-methanoazocino[4,3-b]indole;
5-[(4-chlorophenyl)sulfonyl]-8-methyl-2,3,4,5-tetrahydro-1,4-ethanopyrido[3,2-b]indole;
6-isoquinolin-7-yl-9-methyl-3,4,5,6-tetrahydro-1H-2,5-ethanoazepino[4,3-b]indole;
9-methyl-6-quinolin-6-yl-3,4,5,6-tetrahydro-1H-2, 5-ethanoazepino[4,3-b]indole;
9-methyl-6-(2-methylquinolin-6-yl)-3,4,5, 6-tetrahydro-1H-2, 5-ethanoazepino[4,3-b]indole;
9-methyl-6-quinazolin-6-yl-3,4,5,6-tetrahydro-1H-2,5-ethanoazepino[4,3-b]indole;
6-(9-methyl-1,3,4,5-tetrahydro-6H-2,5-ethanoazepino[4,3-b]indol-6-yl)quinazolin-4-ol;
6-(4-methoxyquinazolin-6-yl)-9-methyl-3,4,5,6-tetrahydro-1H-2,5-ethanoazepino[4,3-b]indole;
9-methyl-6-quinolin-2-yl-3,4,5,6-tetrahydro-1H-2, 5-ethanoazepino[4,3-b]indole;
9-fluoro-6-isoquinolin-7-yl-3,4,5,6-tetrahydro-1H-2,5-ethanoazepino[4,3-b]indole;
9-fluoro-6-quinolin-2-yl-3,4,5,6-tetrahydro-1H-2,5-ethanoazepino[4,3-b]indole;
9-fluoro-6-[6-(1H-pyrazol-1-yl)pyridin-2-yl]-3,4,5,6-tetrahydro-1H-2,5-ethanoazepino[4,3-b]indole;
9-fluoro-6-quinolin-7-yl-3,4,5,6-tetrahydro-1H-2,5-ethanoazepino[4,3-b]indole;
9-fluoro-6-quinazolin-6-yl-3,4,5,6-tetrahydro-1H-2,5-ethanoazepino[4,3-b]indole;
9-fluoro-6-quinolin-6-yl-3,4,5,6-tetrahydro-1H-2,5-ethanoazepino[4,3-b]indole;
9-fluoro-6-(2-methylquinolin-6-yl)-3,4,5,6-tetrahydro-1H-2,5-ethanoazepino[4,3-b]indole;
6-(4-methoxyquinazolin-6-yl)-3,4,5,6-tetrahydro-1H-2, 5-ethanoazepino[4,3-b]indole;
6-(1,3,4,5-tetrahydro-6H-2,5-ethanoazepino[4,3-b]indol-6-yl)quinazolin-4-ol;
6-(2-methylquinolin-6-yl)-3,4,5,6-tetrahydro-1H-2, 5-ethanoazepino[4,3-b]indole;
6-quinolin-6-yl-3,4,5,6-tetrahydro-1H-2,5-ethanoazepino[4,3-b]indole;
6-quinolin-7-yl-3,4,5,6-tetrahydro-1H-2,5-ethanoazepino[4,3-b]indole;
6-quinolin-2-yl-3,4,5,6-tetrahydro-1H-2,5-ethanoazepino[4,3-b]indole;
6-[6-(1H-pyrazol-1-yl)pyridin-2-yl]-3,4,5,6-tetrahydro-1H-2,5-ethanoazepino[4,3-b]indole;
6-[4-(4-methylpiperazin-1-yl)phenyl]-3,4,5,6-tetrahydro-1H-2,5-ethanoazepino[4,3-b]indole;
2-[2-(9-fluoro-1,3,4,5-tetrahydro-6H-2,5-ethanoazepino[4,3-b]indol-6-yl)ethyl]pyridazin-3 (2H)-one;
1-[4-(1,3,4,5-tetrahydro-6H-2, 5-ethanoazepino[4,3-b]indol-6-yl)phenyl]pyridin-2(1H)-one;
9-fluoro-6-[(2-phenylpyrimidin-5-yl)methyl]-3,4,5,6-tetrahydro-1H-2,5-ethanoazepino[4,3-b]indole;
6-(1H-benzimidazol-2-ylmethyl)-9-fluoro-3,4,5,6-tetrahydro-1H-2,5-ethanoazepino[4,3-b]indole;
9-fluoro-6-(quinolin-8-ylmethyl)-3,4,5,6-tetrahydro-1H-2,5-ethanoazepino[4,3-b]indole;
9-fluoro-6-[(3-methyl-1,2-oxazol-5-yl)methyl]-3,4,5,6-tetrahydro-1H-2, 5-ethanoazepino[4,3-b]indole;
6-[(6-chloroimidazo[1,2-b]pyridazin-2-yl)methyl]-9-fluoro-3,4,5,6-tetrahydro-1H-2, 5-ethanoazepino[4,3-b]indole;
9-fluoro-6-(imidazo[1,2-a]pyrimidin-2-ylmethyl)-3,4,5,6-tetrahydro-1H-2,5-ethanoazepino[4,3-b]indole;
6-[(6-chloroimidazo[1,2-b]pyridazin-2-yl)methyl]-3,4,5,6-tetrahydro-1H-2,5-ethanoazepino[4,3-b]indole;
6′-(9-fluoro-1,3,4,5-tetrahydro-6H-2,5-ethanoazepino[4,3-b]indol-6-yl)-2H-1,2′-bipyridin-2-one;
6-(9-fluoro-1,3,4,5-tetrahydro-6H-2,5-ethanoazepino[4,3-b]indol-6-yl)quinazolin-4-ol;
7-(9-fluoro-1,3,4,5-tetrahydro-6H-2, 5-ethanoazepino[4,3-b]indol-6-yl)quinoxalin-2(1H)-one;
7-(9-fluoro-1,3,4,5-tetrahydro-6H-2,5-ethanoazepino[4,3-b]indol-6-yl)-4H-pyrido[1,2-a]pyrimidin-4-one;
2-[6-(9-fluoro-1,3,4,5-tetrahydro-6H-2,5-ethanoazepino[4,3-b]indol-6-yl)pyridin-3-yl]pyridazin-3 (2H)-one;
9-fluoro-6-(2-methylpyrimidin-5-yl)-3,4,5, 6-tetrahydro-1H-2,5-ethanoazepino[4,3-b]indole;
9-fluoro-6-(pyridin-3-yl)-3,4,5,6-tetrahydro-1H-2,5-ethanoazepino[4,3-b]indole;
6-[6-(morpholin-4-yl)pyridin-2-yl]-3,4,5,6-tetrahydro-1H-2,5-ethanoazepino[4,3-b]indole;
6-(1,3,4,5-tetrahydro-6H-2, 5-ethanoazepino[4,3-b]indol-6-yl)nicotinamide;
6-(1,2,3,4-tetrahydroisoquinolin-6-yl)-3,4,5,6-tetrahydro-1H-2,5-ethanoazepino[4,3-b]indole;
6-(2-methyl-1,2,3,4-tetrahydroisoquinolin-6-yl)-3,4,5,6-tetrahydro-1H-2,5-ethanoazepino[4,3-b]indole;
6-(quinazolin-6-yl)-3,4,5,6-tetrahydro-1H-2,5-ethanoazepino[4,3-b]indole;
6-(isoquinolin-7-yl)-3,4,5,6-tetrahydro-1H-2, 5-ethanoazepino[4,3-b]indole;
6-(isoquinolin-6-yl)-3,4,5,6-tetrahydro-1H-2, 5-ethanoazepino[4,3-b]indole;
6-[4-(1H-imidazol-1-yl)pyridin-2-yl]-3,4,5,6-tetrahydro-1H-2,5-ethanoazepino[4,3-b]indole;
6′-(1,3,4,5-tetrahydro-6H-2, 5-ethanoazepino[4,3-b]indol-6-yl)-2H-1,2′-bipyridin-2-one;
7-(1,3,4,5-tetrahydro-6H-2, 5-ethanoazepino[4,3-b]indol-6-yl)quinoxalin-2(1H)-one;
7-(1,3,4,5-tetrahydro-6H-2, 5-ethanoazepino[4,3-b]indol-6-yl)-2H-1,4-benzoxazin-3 (4H)-one;
2-amino-5-(1,3,4,5-tetrahydro-6H-2,5-ethanoazepino[4,3-b]indol-6-yl)benzamide;
7-(1,3,4,5-tetrahydro-6H-2,5-ethanoazepino[4,3-b]indol-6-yl)-4H-pyrido[1,2-a]pyrimidin-4-one;
(7S,10R)-5-(quinolin-6-yl)-5,6,7,8,9,10-hexahydro-7,10-epiminocyclohepta[b]indole;
(7R,10S)-5-(isoquinolin-7-yl)-5,6,7,8,9,10-hexahydro-7,10-epiminocyclohepta[b]indole;
(7S,10R)-5-(isoquinolin-7-yl)-5,6,7,8,9,10-hexahydro-7,10-epiminocyclohepta[b]indole;
(7S,10R)-11-methyl-5-(quinolin-6-yl)-5,6,7,8,9,10-hexahydro-7,10-epiminocyclohepta[b]indole;
(7R,10S)-5-(quinolin-6-yl)-5,6,7,8,9,10-hexahydro-7,10-epiminocyclohepta[b]indole;
7-[(7S,10R)-7,8,9,10-tetrahydro-7,10-epiminocyclohepta[b]indol-5(6H)-yl]-4H-pyrido[1,2-a]pyrimidin-4-one;
7-[(7R,10S)-7,8,9,10-tetrahydro-7,10-epiminocyclohepta[b]indol-5(6H)-yl]-4H-pyrido[1,2-a]pyrimidin-4-one;
6-[(6-chloropyridin-3-yl)methyl]-9-fluoro-1,2,3,4,5,6-hexahydro-1,4-methanoazepino[4,3-b]indole;
(7R,10S)-11-methyl-5-(quinolin-6-yl)-5,6,7,8,9,10-hexahydro-7,10-epiminocyclohepta[b]indole;
and
2-[4-(1,3,4,5-tetrahydro-6H-2, 5-ethanoazepino[4,3-b]indol-6-yl)phenyl]pyridazin-3 (2H)-one.

252 more elements

Dependencies are inferred from the claim text.

Facts

Application

15/454,313Filed 9 Mar 2017

Priority

29 Sep 2008

Published

25 Jan 2018

Term ends

Not estimatedThe source records don’t support an estimate.

Classification15 codes

G01N 33/6896
Related to diseases not provided for elsewhere: neurological disorders, e.g. Alzheimer's disease
A61P 25/00
Drugs for disorders of the nervous system
A61P 25/02
Drugs for disorders of the nervous system: for peripheral neuropathies
A61P 25/16
For treating abnormal movements, e.g. chorea, dyskinesia: anti-Parkinson drugs

Family

Application61/101,054Us provisional application · filed 29 Sep 2008

Application61/225,452Us provisional application · filed 14 Jul 2009

Application12/568,085Continuation in part · filed 28 Sep 2009

Application12/727,723Division · filed 19 Mar 2010

Application15/454,313Division

Application12/727,723Continuation in part

US 2010/0087471 A1Published application

US 2010/0249105 A1Published application

US 9,063,126 B2Related patent

US 9,625,475 B2Related patent

US 9,983,218 B2Related patent

US 2018/0024144 A1This patent

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

Indole and indoline derivatives and methods of use thereof

Life of this patent

Indole and indoline derivatives and methods of use thereof

Life of this patent

Abstract

Claims3