4-Azaindole Derivatives

摘要

4-Azaindole derivatives which are modulators of muscarinic acetylcholine receptor (mAChR) M1 and which may be effective for the prevention or disease modifying or symptomatic treatment of cognitive deficits associated with neurological disorders such as Alzheimer-type dementia (AD) or dementia with Lewy bodies (DLB), and a pharmaceutical composition comprising a 4-azaindole derivative as an active ingredient.

主权项

1. A compound or a pharmaceutically acceptable salt thereof, which is
N-((1S,2S)-2-hydroxycyclohexyl)-1-(4-methylbenzyl)-1H-pyrrolo[3,2-b]pyridine-3-carboxamide; 1-(3,5-difluorobenzyl)-N-((1S,2S)-2-hydroxycyclohexyl)-1H-pyrrolo[3,2-b]pyridine-3-carboxamide; 1-(2,5-difluorobenzyl)-N-((1S,2S)-2-hydroxycyclohexyl)-1H-pyrrolo[3,2-b]pyridine-3-carboxamide; 1-(3-fluorobenzyl)-N-((1S,2S)-2-hydroxycyclohexyl)-1H-pyrrolo[3,2-b]pyridine-3-carboxamide; 1-(4-fluorobenzyl)-N-((1S,2S)-2-hydroxycyclohexyl)-1H-pyrrolo[3,2-b]pyridine-3-carboxamide; 1-(4-fluoro-3-methylbenzyl)-N-((1S,2S)-2-hydroxycyclohexyl)-1H-pyrrolo[3,2-b]pyridine-3-carboxamide; 1-(2,3-difluorobenzyl)-N-((1S,2S)-2-hydroxycyclohexyl)-1H-pyrrolo[3,2-b]pyridine-3-carboxamide; N-((1S,2S)-2-hydroxycyclohexyl)-1-(4-(trifluoromethoxy)benzyl)-1H-pyrrolo[3,2-b]pyridine-3-carboxamide; 1-(4-fluorobenzyl)-N-((1S,2S)-2-hydroxycyclohexyl)-7-methyl-1H-pyrrolo[3,2-b]pyridine-3-carboxamide; 1-(2,3-difluorobenzyl)-N-((1S,2S)-2-hydroxycyclohexyl)-7-methyl-1H-pyrrolo[3,2-b]pyridine-3-carboxamide; N-((1S,2S)-2-hydroxycyclohexyl)-1-(4-methoxybenzyl)-7-methyl-1H-pyrrolo[3,2-b]pyridine-3-carboxamide; 1-(3-fluoro-4-methoxybenzyl)-N-((1S,2S)-2-hydroxycyclohexyl)-7-methyl-1H-pyrrolo[3,2-b]pyridine-3-carboxamide; 7-chloro-1-(4-fluorobenzyl)-N-((1S,2S)-2-hydroxycyclohexyl)-1H-pyrrolo[3,2-b]pyridine-3-carboxamide; 7-chloro-1-(2,3-difluorobenzyl)-N-((1S,2S)-2-hydroxycyclohexyl)-1H-pyrrolo[3,2-b]pyridine-3-carboxamide; 7-chloro-N-((1S,2S)-2-hydroxycyclohexyl)-1-((6-methylpyridin-2-yl)methyl)-1H-pyrrolo[3,2-b]pyridine-3-carboxamide; 7-chloro-1-((5-fluoropyridin-2-yl)methyl)-N-((1S,2S)-2-hydroxycyclohexyl)-1H-pyrrolo[3,2-b]pyridine-3-carboxamide; 1-(2-fluorobenzyl)-N-((1S,2S)-2-hydroxycyclohexyl)-1H-pyrrolo[3,2-b]pyridine-3-carboxamide; 1-(4-chlorobenzyl)-N-((1S,2S)-2-hydroxycyclohexyl)-1H-pyrrolo[3,2-b]pyridine-3-carboxamide; 1-(2,4-difluorobenzyl)-N-((1S,2S)-2-hydroxycyclohexyl)-1H-pyrrolo[3,2-b]pyridine-3-carboxamide; 1-(4-fluorobenzyl)-N-(trans-2-hydroxycycloheptyl)-1H-pyrrolo[3,2-b]pyridine-3-carboxamide; 1-(4-fluorobenzyl)-N-(piperidin-4-yl)-1H-pyrrolo[3,2-b]pyridine-3-carboxamide; 1-(4-fluorobenzyl)-N-(1-methylpiperidin-4-yl)-1H-pyrrolo[3,2-b]pyridine-3-carboxamide; 7-cyano-1-(4-fluorobenzyl)-N-((1S,2S)-2-hydroxycyclohexyl)-1H-pyrrolo[3,2-b]pyridine-3-carboxamide; 7-cyano-N-((1S,2S)-2-hydroxycyclohexyl)-1-(4-(trifluoromethyl)benzyl)-1H-pyrrolo[3,2-b]pyridine-3-carboxamide; N-(trans-4,4-difluoro-2-hydroxycyclohexyl)-1-(4-fluorobenzyl)-1H-pyrrolo[3,2-b]pyridine-3-carboxamide; 1-(4-fluorobenzyl)-N-((1S,2S)-2-hydroxycyclohexyl)-7-methoxy-1H-pyrrolo[3,2-b]pyridine-3-carboxamide; 1-(4-(1H-pyrazol-1-yl)benzyl)-N-((1S,2S)-2-hydroxycyclohexyl)-5-methyl-1H-pyrrolo[3,2-b]pyridine-3-carboxamide; 1-(4-(1H-pyrazol-1-yl)benzyl)-5-cyano-N-((1S,2S)-2-hydroxycyclohexyl)-1H-pyrrolo[3,2-b]pyridine-3-carboxamide; N-((1S,2S)-2-hydroxycyclohexyl)-1-(4-(1-methyl-1H-imidazol-2-yl)benzyl)-1H-pyrrolo[3,2-b]pyridine-3-carboxamide; N-((1S,2S)-2-hydroxycyclohexyl)-1-(4-(1-methyl-1H-imidazol-4-yl)benzyl)-1H-pyrrolo[3,2-b]pyridine-3-carboxamide; 1-(2-fluoro-4-(6-methylpyridin-2-yl)benzyl)-N-((1S,2S)-2-hydroxycyclohexyl)-1H-pyrrolo[3,2-b]pyridine-3-carboxamide; 1-(2-fluoro-4-(2-methylpyridin-4-yl)benzyl)-N-((1S,2S)-2-hydroxycyclohexyl)-1H-pyrrolo[3,2-b]pyridine-3-carboxamide; 1-((4′-fluoro-[1,1′-biphenyl]-4-yl)methyl)-N-(trans-2-hydroxycyclohexyl)-1H-pyrrolo[3,2-b]pyridine-3-carboxamide; 1-(4-(1H-pyrazol-1-yl)benzyl)-N-((1S,2S)-2-hydroxycyclohexyl)-1H-pyrrolo[3,2-b]pyridine-3-carboxamide; 1-(4-(1H-pyrazol-1-yl)benzyl)-N-((1R,2R)-2-hydroxycyclohexyl)-1H-pyrrolo[3,2-b]pyridine-3-carboxamide; 1-(4-(1H-pyrazol-1-yl)benzyl)-N-cyclohexyl-1H-pyrrolo[3,2-b]pyridine-3-carboxamide; 1-(4-(1H-pyrazol-1-yl)benzyl)-N-(4,4-difluorocyclohexyl)-1H-pyrrolo[3,2-b]pyridine-3-carboxamide; (S)-1-(4-(1H-pyrazol-1-yl)benzyl)-N-(piperidin-3-yl)-1H-pyrrolo[3,2-b]pyridine-3-carboxamide; (S)-1-(4-(1H-pyrazol-1-yl)benzyl)-N-(1-methylpiperidin-3-yl)-1H-pyrrolo[3,2-b]pyridine-3-carboxamide; (R)-1-(4-(1H-pyrazol-1-yl)benzyl)-N-(1-methylpiperidin-3-yl)-1H-pyrrolo[3,2-b]pyridine-3-carboxamide; 1-(4-bromobenzyl)-N-((1S,2S)-2-hydroxycyclohexyl)-1H-pyrrolo[3,2-b]pyridine-3-carboxamide; N-((1S,2S)-2-hydroxycyclohexyl)-1-(4-(1-methyl-1H-pyrazol-4-yl)benzyl)-1H-pyrrolo[3,2-b]pyridine-3-carboxamide; 7-chloro-N-((1S,2S)-2-hydroxycyclohexyl)-1-(4-methoxybenzyl)-1H-pyrrolo[3,2-b]pyridine-3-carboxamide; 1-((6-chloropyridin-3-yl)methyl)-N-((1S,2S)-2-hydroxycyclohexyl)-7-methyl-1H-pyrrolo[3,2-b]pyridine-3-carboxamide; 1-(4-chlorobenzyl)-N-((1S,2S)-2-hydroxycyclohexyl)-7-methyl-1H-pyrrolo[3,2-b]pyridine-3-carboxamide; 7-chloro-N-((1S,2S)-2-hydroxycyclohexyl)-1-((5-methylpyridin-2-yl)methyl)-1H-pyrrolo[3,2-b]pyridine-3-carboxamide; 7-chloro-N-((1S,2S)-2-hydroxycyclohexyl)-1-((6-methylpyridin-3-yl)methyl)-1H-pyrrolo[3,2-b]pyridine-3-carboxamide; N-((1S,2S)-2-hydroxycyclohexyl)-7-methyl-1-(4-methylbenzyl)-1H-pyrrolo[3,2-b]pyridine-3-carboxamide; N-((1S,2S)-2-hydroxycyclohexyl)-7-methyl-1-((5-methylpyridin-2-yl)methyl)-1H-pyrrolo[3,2-b]pyridine-3-carboxamide; 1-(3-fluorobenzyl)-N-((1S,2S)-2-hydroxycyclohexyl)-7-methyl-1H-pyrrolo[3,2-b]pyridine-3-carboxamide; N-((1S,2S)-2-hydroxycyclohexyl)-1-(4-methoxy-3-methylbenzyl)-7-methyl-1H-pyrrolo[3,2-b]pyridine-3-carboxamide; N-((1S,2S)-2-hydroxycyclohexyl)-1-((6-methoxypyridin-3-yl)methyl)-7-methyl-1H-pyrrolo[3,2-b]pyridine-3-carboxamide; 7-chloro-N-((1S,2S)-2-hydroxycyclohexyl)-1-((6-methoxypyridin-3-yl)methyl)-1H-pyrrolo[3,2-b]pyridine-3-carboxamide; 7-chloro-N-((1S,2S)-2-hydroxycyclohexyl)-1-((2-methoxypyridin-4-yl)methyl)-1H-pyrrolo[3,2-b]pyridine-3-carboxamide; 7-chloro-1-((6-cyanopyridin-3-yl)methyl)-N-((1S,2S)-2-hydroxycyclohexyl)-1H-pyrrolo[3,2-b]pyridine-3-carboxamide; N-((1S,2S)-2-hydroxycyclohexyl)-1-((2-methoxypyridin-4-yl)methyl)-7-methyl-1H-pyrrolo[3,2-b]pyridine-3-carboxamide; 7-chloro-N-((1S,2S)-2-hydroxycyclohexyl)-1-((1-methyl-1H-pyrazol-4-yl)methyl)-1H-pyrrolo[3,2-b]pyridine-3-carboxamide; N-((1S,2S)-2-hydroxycyclohexyl)-7-methyl-1-((1-methyl-1H-pyrazol-4-yl)methyl)-1H-pyrrolo[3,2-b]pyridine-3-carboxamide; 7-chloro-N-((1S,2S)-2-hydroxycyclohexyl)-1-((4-methylthiazol-2-yl)methyl)-1H-pyrrolo[3,2-b]pyridine-3-carboxamide; 7-chloro-N-((1S,2S)-2-hydroxycyclohexyl)-1-((5-methylthiazol-2-yl)methyl)-1H-pyrrolo[3,2-b]pyridine-3-carboxamide; N-((1S,2S)-2-hydroxycyclohexyl)-1-((2-methylpyridin-4-yl)methyl)-1H-pyrrolo[3,2-b]pyridine-3-carboxamide; N-((1S,2S)-2-hydroxycyclohexyl)-1-(pyridin-4-ylmethyl)-1H-pyrrolo[3,2-b]pyridine-3-carboxamide; 7-chloro-N-((1S,2S)-2-hydroxycyclohexyl)-1 ((2-methylpyridin-4-yl)methyl)-1H-pyrrolo[3,2-b]pyridine-3-carboxamide; 7-chloro-N-((1S,2S)-2-hydroxycyclohexyl)-1-(pyridin-4-ylmethyl)-1H-pyrrolo[3,2-b]pyridine-3-carboxamide; 7-chloro-N-((1S,2S)-2-hydroxycyclohexyl)-1-((4-methylpyridin-2-yl)methyl)-1H-pyrrolo[3,2-b]pyridine-3-carboxamide; 1-((5-chloropyridin-2-yl)methyl)-N-((1S,2S)-2-hydroxycyclohexyl)-7-methyl-1H-pyrrolo[3,2-b]pyridine-3-carboxamide; 1-(4-fluorobenzyl)-N-(trans-3-hydroxytetrahydro-2H-pyran-4-yl)-7-methyl-1H-pyrrolo[3,2-b]pyridine-3-carboxamide; 1-(4-methoxybenzyl)-N-(trans-3-hydroxytetrahydro-2H-pyran-4-yl)-7-methyl-1H-pyrrolo[3,2-b]pyridine-3-carboxamide; 1-(3-fluoro-4-methoxybenzyl)-N-(trans-3-hydroxytetrahydro-2H-pyran-4-yl)-7-methyl-1H-pyrrolo[3,2-b]pyridine-3-carboxamide; N-(trans-3-hydroxytetrahydro-2H-pyran-4-yl)-1-((2-methoxypyridin-4-yl)methyl)-7-methyl-1H-pyrrolo[3,2-b]pyridine-3-carboxamide; 7-chloro-1-(3-fluorobenzyl)-N-(trans-3-hydroxytetrahydro-2H-pyran-4-yl)-1H-pyrrolo[3,2-b]pyridine-3-carboxamide; 7-chloro-1-(4-methoxybenzyl)-N-(trans-3-hydroxytetrahydro-2H-pyran-4-yl)-1H-pyrrolo[3,2-b]pyridine-3-carboxamide; 7-chloro-1-(4-fluorobenzyl)-N-((3R,4S)-3-hydroxytetrahydro-2H-pyran-4-yl)-1H-pyrrolo[3,2-b]pyridine-3-carboxamide; or 7-chloro-1-(4-fluorobenzyl)-N-((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)-1H-pyrrolo[3,2-b]pyridine-3-carboxamide.