Quinoline amide m1 receptor positive allosteric modulators

Abstract

The present invention is directed to quinoline amide compounds of formula (I) which are M1 receptor positive allosteric modulators and that are useful in the treatment of diseases in which the M1 receptor is involved, such as Alzheimer's disease, schizophrenia, pain or sleep disorders. The invention is also directed to pharmaceutical compositious comprising the compounds, and to the use of the compounds and compositions in the treatment of diseases mediated by the M1 receptor.

What is claimed is: 
     
         1 . A compound of formula (I): 
       
         
           
           
               
               
           
         
       
       wherein 
       X 1  is selected from the group consisting of
 (1) N, and 
 (2) N→O; 
 
       X 2 -X 3  is selected from the group consisting of
 (1) —CH 2 —CH 2 —, 
 (2) —O—CH 2 —, 
 (3) —CH 2 —O—, or 
 (4) —CH 2 —; 
 
       X 4 , X 5 , X 6  X 7  are each selected from the group consisting of
 (1) N, 
 (2) N→O, 
 (3) CH, 
 (4) O 
 
       provided that one of X 4 , X 5 , X 6  and X 7  may be absent, thereby forming a five-membered ring; 
       R 1  is selected from the group consisting of
 (1) hydrogen, 
 (2) halogen, 
 (3) —C 1-6  alkyl, 
 (4) —C 2-6  alkynyl, 
 (4) phenyl, 
 (5) ═O, 
 (6) ═CH 2 , 
 (7) hydroxyl, 
 wherein the R 1  alkyl, alkynyl or phenyl group is optionally substituted with one or more
 (a) hydroxyl, or 
 (b) halogen; 
 
 
       R 2A  and R 2B  are independently selected from the group consisting of
 (1) hydrogen, 
 (2) hydroxyl, and 
 (3) halogen, 
 or R 2A  and R 2B  together from ═O; 
 
       R 3  is optionally present at one or more of the ring carbon atoms, and is independently selected from the group consisting of
 (1) halogen, 
 (2) —O—C 1-6  alkyl, 
 (3) —S—C 1-6  alkyl, or 
 (4) a heteroaryl group, which is an aromatic cyclic group, having from five to twelve ring atoms, said ring atoms selected from C, O, N, N→O or S, at least one of which is O, N, N→O or S, wherein the heteroaryl is optionally substituted with C 1-6  alkyl; 
 
       R 4  is optionally present at one or more of the ring atoms, and is selected from the group consisting of
 (1) hydroxyl 
 (2) halogen, 
 (3) —C 1-6  alkyl, 
 (4) —O—C 1-6  alkyl, 
 (5) —S—C 1-6  alkyl, 
 (6) —C 3-8  cycloalkyl, 
 (7) —C 6-10  aryl, 
 (8) —CN, 
 (9) a heteroaryl group, which is an aromatic cyclic group, having from five to twelve ring atoms, said ring atoms selected from C, O, N, N→O or S, at least one of which is O, N, N→O or S, 
 (10) —O-heterocyclyl, 
 (11) —NR A R B , 
 wherein R A  and R B  are selected from the group consisting of
 (a) hydrogen, or 
 (b) —C 1-6  alkyl, 
 
 or R A  and R B  are linked together with the nitrogen to which they are attached to form a 4-6 membered carbocyclic ring, wherein one or two of the ring carbon atoms is optionally replaced by a nitrogen, oxygen or sulfur, and the ring is optionally substituted with one or more
 (a) halogen, 
 (b) hydroxyl, 
 (c) C 1-6  alkyl, 
 (d) —O—C 1-6  alkyl, 
 (e) —C(═O)—(O) n —C 1-6  alkyl; 
 
 wherein n is 0-1; and the alkyl, cycloalkyl, aryl or heteroaryl R 4  group is optionally substituted with one or more
 (a) halogen, 
 (b) hydroxy, 
 (c) —O—C 1-6  alkyl, 
 (d) —C 1-6  alkyl, 
 (e) —S—C 1-6  alkyl, or 
 (f) a heteroaryl group, which is an aromatic cyclic group, having from five to twelve ring atoms, said ring atoms selected from C, O, N, N→O or S, at least one of which is O, N, N→O or S, 
 wherein the alkyl, aryl or heteroaryl moiety is optionally substituted with one or more
 (i) halogen, 
 (ii) hydroxy, 
 (iii) —O—C 1-6  alkyl, or 
 (iv) —C 1-6  alkyl; 
 
 
 or two R 4  groups are linked together to form a three or four atom fused ring heteroaryl group, said ring atoms selected from C, O, N, N→O or S, at least one of which is O, N, N→O or S, 
 
       or a pharmaceutically acceptable salt thereof. 
     
     
         2 . A compound of  claim 1 , or a pharmaceutically acceptable salt thereof, wherein one or two of X 4 , X 5 , X 6  and X 7  is N or N→O and the others are each CH or C substituted with R 4 . 
     
     
         3 . A compound of  claim 1  or a pharmaceutically acceptable salt thereof, wherein X 1  is N. 
     
     
         4 . A compound of  claim 1  or a pharmaceutically acceptable salt thereof, wherein X 2 -X 3  is —CH 2 —CH 2 — —O—CH 2 — or —CH 2 —O—. 
     
     
         5 . A compound of  claim 1  or a pharmaceutically acceptable salt thereof, wherein X 4  is N and X 5 , X 6  and X 7  are each CH, or X 4 , X 6  and X 7  are each CH and X 5  is N, or X 4  and X 6  are each N, X 7  is CH, and X 5  is C substituted with R 4 . 
     
     
         6 . A compound of  claim 1  or a pharmaceutically acceptable salt thereof, wherein R 1  is halogen. 
     
     
         7 . A compound of  claim 1  or a pharmaceutically acceptable salt thereof, wherein R 2A  and R 2B  are each hydrogen, or R 2A  is hydrogen and R 2B  is halogen. 
     
     
         8 . A compound of  claim 1  or a pharmaceutically acceptable salt thereof, wherein R 3A  and R 3B  are each hydrogen, or R 3A  is halogen and R 3B  is hydrogen. 
     
     
         9 . A compound of  claim 1  or a pharmaceutically acceptable salt thereof, wherein each of R 2A , R 2B , R 3A  and R 3B  is hydrogen. 
     
     
         10 . A compound of  claim 1  or a pharmaceutically acceptable salt thereof, wherein R 4  is present at one of the ring atoms, and is selected from the group consisting of
 (1) halogen, 
 (2) —C 1-6  alkyl, or 
 (3) a heteroaryl group, which is an aromatic cyclic group, having from five to twelve ring atoms, said ring atoms selected from C, O, N, N→O or S, at least one of which is O, N, N→O or S, 
 wherein said alkyl or heteroaryl R 4  group is optionally substituted with one or more
 (a) halogen, 
 (b) hydroxy, 
 (c) —O—C 1-6  alkyl, 
 (d) —C 1-6  alkyl, optionally substituted with halogen, or 
 (e) —S—C 1-6  alkyl. 
 
 
     
     
         11 . A compound  claim 1 , in which the compound of formula (I) is a compound of formula (II): 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof, wherein X 2 , X 3 , R 1 , R 2A , R 2B , R 3A , R 3B  and R 4  are as defined in  claim 1 . 
     
     
         12 . A compound of  claim 11 , or a pharmaceutically acceptable salt thereof, wherein X 2 -X 3  is —CH 2 —CH 2 — —O—CH 2 — or —CH 2 —O—. 
     
     
         13 . A compound of  claim 11  or a pharmaceutically acceptable salt thereof, wherein R 1  is halogen. 
     
     
         14 . A compound of  claim 11  or a pharmaceutically acceptable salt thereof, wherein R 2A  and R 2B  are each hydrogen, or R 2A  is hydrogen and R 2B  is halogen. 
     
     
         15 . A compound of  claim 11  or a pharmaceutically acceptable salt thereof, wherein R 4  is selected from the group consisting of
 (1) a heteroaryl group, which is an aromatic cyclic group, having from five to twelve ring atoms, said ring atoms selected from C, O, N or S, at least one of which is O, N or S, 
 (2) halogen, 
 (3) hydroxy, 
 (4) —O—C 1-6  alkyl, 
 (5) —C 1-6  alkyl, or 
 (6) —S—C 1-6  alkyl, 
 wherein said alkyl or heteroaryl R 4  moiety is optionally substituted with one or more
 (a) halogen, 
 (b) hydroxy, 
 (c) —O—C 1-6  alkyl, 
 (d) —C 1-6  alkyl, optionally substituted with halogen, or 
 (e) —S—C 1-6  alkyl. 
 
 
     
     
         16 . A compound of  claim 1 , in which the compound of formula (I) is a compound of formula (III): 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof, wherein X 2 , X 3 , R 1 , R 2A , R 2B , R 3A , R 3B  and R 4  are as described above. 
     
     
         17 . A compound of  claim 16 , or a pharmaceutically acceptable salt thereof, wherein X 2 -X 3  is —CH 2 —CH 2 —, —O—CH 2 — or —CH 2 —O—. 
     
     
         18 . A compound of  claim 1 , which is selected from the group consisting of: 
       4-[(6-Chloropyridin-3-yl)methyl]-N-[(1S,2S)-2-hydroxycyclohexyl]quinoline-2-carboxamide; 
       N-[(1S,2S)-2-Hydroxycyclohexyl]-4-[(6-methylpyridin-3-yl)methyl]quinoline-2-carboxamide; 
       4-[(6-Chloropyridin-3-yl)methyl]-N-[(1S,2S)-2-hydroxycyclohexyl]quinoline-2-carboxamide 1-oxide; 
       4-[(6-Cyclopropylopyridin-3-yl)methyl]-N-[(1,2)-2-hydroxycyclohexyl]quinoline-2-carboxamide; 
       N-[(1S,2S)-2-Hydroxycyclohexyl]-4-{[6-(1-methyl-1H-pyrazol-4-yl)pyridin-3-yl]methyl}quinoline-2-carboxamide; 
       N-[(1S,2S)-2-Hydroxycyclohexyl]-4-pyridin-3-ylmethyl)quinoline-2-carboxamide; 
       N-[(1S,2S)-2-Hydroxycyclohexyl]-4-{[6-(methylsulfanyl)pyridin-3-yl]methyl}quinoline-2-carboxamide; 
       N-[(1S,2S)-2-Hydroxycyclohexyl]-4-{[6-(1-methyl-1H-pyrazol-4-yl)-1-oxidopyridin-3-yl]methyl}quinoline-2-carboxamide; 
       N-[(1S,2S)-2-Fluorocyclohexyl]-4-{[6-(1-methyl-1H-pyrazol-4-yl)pyridin-3-yl]methyl}quinoline-2-carboxamide; 
       N-[(3S,4S)-4-Hydroxytetrahydro-2H-pyran-3-yl]-4-{[6-(1-methyl-1H-pyrazol-4-yl)pyridin-3-yl]methyl}quinoline-2-carboxamide; 
       N-[(3S,4S)-3-Hydroxytetrahydro-2H-pyran-4-yl]-4-[(6-methoxypyridin-3-yl)methyl]quinoline-2-carboxamide; 
       4-[(6-Ethoxypyridin-3-yl)methyl]-N-[(3R,4S)-3-hydroxytetrahydro-2H-pyran-4-yl]quinoline-2-carboxamide; 
       N-[(3R,4S)-3-Hydroxytetrahydro-2H-pyran-4-yl]-4-[(2-methoxypyridin-3-yl)methyl]quinoline-2-carboxamide; 
       N-[(3R,4S)-3-Hydroxytetrahydro-2H-pyran-4-yl]-4-{[2-(methylsulfanyl)pyrimidin-5-yl]methyl}quinoline-2-carboxamide; 
       4-[Fluoro(6-methoxypyridin-3-yl)methyl]-N-[(3R,4S)-3-hydroxytetrahydro-2H-pyran-4-yl]quinoline-2-carboxamide hydrate; 
       4-[(6-Chloropyridin-3-yl)methyl]-8-fluoro-N-[(3R,4S)-3-hydroxytetrahydro-2H-pyran-4-yl]quinoline-2-carboxamide; 
       4-{[6-(Difluoromethyl)pyridin-3-yl]methyl}-8-fluoro-N-[(3R,4S)-3-hydroxytetrahydro-2H-pyran-4-yl]quinoline-2-carboxamide; 
       4-[Fluoro(6-methoxypyridin-3-yl)methyl]-N-[(3R,4S)-3-hydroxytetrahydro-2H-pyran-4-yl]-8-methoxyquinoline-2-carboxamide; 
       8-Fluoro-N-[(3R,4S)-3-hydroxytetrahydro-2H-pyran-4-yl]-4-[(6-methoxypyridin-3-yl)methyl]quinoline-2-carboxamide; 
       8-Fluoro-4-[(6-hydroxypyridin-3-yl)methyl]-N-[(3R,4S)-3-hydroxytetrahydro-2H-pyran-4-yl]quinoline-2-carboxamide; 
       8-Fluoro-N-[(3R,4S)-3-hydroxytetrahydro-2H-pyran-4-yl]-4-[(6-methoxy-1-oxidopyridin-3-yl)methyl]quinoline-2-carboxamide; 
       8-Fluoro-N-[(3R,4S)-3-hydroxytetrahydro-2H-pyran-4-yl]-4-[(2-methoxypyridin-4-yl)methyl]quinoline-2-carboxamide; 
       8-Fluoro-N-[(3R,4S)-3-hydroxytetrahydro-2H-pyran-4-yl]-4-[(2-methoxy-1-oxidopyridin-4-yl)methyl]quinoline-2-carboxamide; 
       5,8-Difluoro-N-[(3R,4S)-3-hydroxytetrahydro-2H-pyran-4-yl]-4-[(6-methoxypyridin-3-yl)methyl]quinoline-2-carboxamide; 
       4-[(6-chloropyridin-3-yl)methyl]-N-[(1S,2S)-2-hydroxycyclohexyl]quinoline-2-carboxamide; 
       N-[(1S,2S)-2-hydroxycyclohexyl]-4-[(6-methylpyridin-3-yl)methyl]quinoline-2-carboxamide; 
       4-[(6-chloropyridin-3-yl)methyl]-N-[(1R,2R)-2-hydroxycyclohexyl]quinoline-2-carboxamide; 
       4-[(6-chloropyridin-3-yl)methyl]-N-(tetrahydro-2H-pyran-3-yl)quinoline-2-carboxamide; 
       4-[(6-chloropyridin-3-yl)methyl]-N-[(1S,2R)-2-hydroxycyclohexyl]quinoline-2-carboxamide; 
       4-[(6-chloropyridin-3-yl)methyl]-N-(tetrahydro-2H-pyran-4-yl)quinoline-2-carboxamide; 
       N-[(1S,2S)-2-hydroxycyclohexyl]-4-(4-methoxybenzyl)quinoline-2-carboxamide; 
       N-[(1S,2S)-2-hydroxycyclohexyl]-4-(4-methoxybenzyl)quinoline-2-carboxamide 1-oxide; 
       N-[(1S,2S)-2-hydroxycyclohexyl]-4-{[6-(1-methyl-1H-pyrazol-4-yl)pyridin-3-yl]methyl}quinoline-2-carboxamide; 
       4-({6-[(6-chloropyridin-3-yl)methyl]pyridin-3-yl}methyl)-N-[(1S,2S)-2-hydroxycyclohexyl]quinoline-2-carboxamide; 
       N-[(1S,2S)-2-hydroxycyclohexyl]-4-(pyridin-3-ylmethyl)quinoline-2-carboxamide; 
       1,5-anhydro-3-[({4-[(6-chloropyridin-3-yl)methyl]quinolin-2-yl}carbonyl)amino]-2,3-dideoxy-L-threo-pentitol; 
       4-[(6-chloropyridin-3-yl)methyl]-N-[(1S,2S)-2-(hydroxymethyl)cyclohexyl]quinoline-2-carboxamide; 
       4-[(6-cyclopropylpyridin-3-yl)methyl]-N-[(1S,2S)-2-hydroxycyclohexyl]quinoline-2-carboxamide; 
       4-[(6-chloropyridin-3-yl)methyl]-N-[(1S,2S)-2-fluorocyclohexyl]quinoline-2-carboxamide; 
       4-[(6-ethylpyridin-3-yl)methyl]-N-[(1S,2S)-2-hydroxycyclohexyl]quinoline-2-carboxamide; 
       N-[(1S,2S)-2-hydroxycyclohexyl]-4-[(6′-methyl-2,3′-bipyridin-5-yl)methyl]quinoline-2-carboxamide; 
       N-[(1S,2S)-2-hydroxycyclohexyl]-4-{[(6-(morpholin-4-yl)pyridin-3-yl]methyl}quinoline-2-carboxamide; 
       N-[(1S,2S)-2-hydroxycyclohexyl]-4-(pyridin-4-ylmethyl)quinoline-2-carboxamide; 
       4-[(6-cyanopyridin-3-yl)methyl]-N-[(1S,2S)-2-hydroxycyclohexyl]quinoline-2-carboxamide; 
       N-[(1S,2S)-2-hydroxycyclohexyl]-4-[4-(1H-pyrazol-1-yl)benzyl]quinoline-2-carboxamide; 
       4-[(3,5-dimethylisoxazol-4-yl)methyl]-N-[(1S,2S)-2-hydroxycyclohexyl]quinoline-2-carboxamide; 
       4-[(6′-fluoro-2,3′-bipyridin-5-yl)methyl]-N-[(1S,2S)-2-hydroxycyclohexyl]quinoline-2-carboxamide; 
       4-[(5′-fluoro-2,3′-bipyridin-5-yl)methyl]-N-[(1S,2S)-2-hydroxycyclohexyl]quinoline-2-carboxamide; 
       4-{[6-(3,5-dimethylisoxazol-4-yl)pyridin-3-yl]methyl}-N-[(1S,2S)-2-hydroxycyclohexyl]quinoline-2-carboxamide; 
       N-[(1S,2S)-2-hydroxycyclohexyl]-4-{[6-(thiophen-3-yl)pyridin-3-yl]methyl}quinoline-2-carboxamide; 
       N-[(1S,2S)-2-hydroxycyclohexyl]-4-{[6-(pyrazin-2-yl)pyridin-3-yl]methyl}quinoline-2-carboxamide; 
       N-[(1S,2S)-2-hydroxycyclohexyl]-4-{[6-(1,3-thiazol-5-yl)pyridin-3-yl]methyl}quinoline-2-carboxamide; 
       N-[(1S,2S)-2-hydroxycyclohexyl]-4-{[6-(1,3-oxazol-2-yl)pyridin-3-yl]methyl}quinoline-2-carboxamide; 
       N-[(1S,2S)-2-hydroxycyclohexyl]-4-{[6-(1H-pyrazol-1-yl)pyridin-3-yl]methyl}quinoline-2-carboxamide; 
       N-[(1S,2S)-2-hydroxycyclohexyl]-4-{[6-(trifluoromethyl)pyridin-3-yl]methyl}quinoline-2-carboxamide; 
       4-[(6-fluoropyridin-3-yl)methyl]-N-[(1S,2S)-2-hydroxycyclohexyl]quinoline-2-carboxamide; 
       4-[(6-chloropyridin-3-yl)methyl]-8-fluoro-N-[(1S,2S)-2-hydroxycyclohexyl]quinoline-2-carboxamide; 
       4-(4-cyanobenzyl)-N-[(1S,2S)-2-hydroxycyclohexyl]quinoline-2-carboxamide; 
       N-[(1S,2S)-2-hydroxycyclohexyl]-4-{[6-(1-methyl-1H-pyrazol-5-yl)pyridin-3-yl]methyl}quinoline-2-carboxamide; 
       N-[(1S,2S)-2-hydroxycyclohexyl]-4-{[6-(pyrimidin-5-yl)pyridin-3-yl]methyl}quinoline-2-carboxamide; 
       N-[(1S,2S)-2-hydroxycyclohexyl]-4-{[6-(2-methoxypyrimidin-t-yl)pyridin-3-yl]methyl}quinoline-2-carboxamide; 
       N-[(1S,2S)-2-hydroxycyclohexyl]-4-[4-(1H-1,2,4-triazol-1-yl)benzyl]quinoline-2-carboxamide; 
       4-(4-chlorobenzyl)-N-[(1S,2S)-2-hydroxycyclohexyl]quinoline-2-carboxamide; 
       4-(4-chlorobenzyl)-N-[(3R,4S)-3-hydroxytetrahydro-2H-pyran-4-yl]quinoline-2-carboxamide; 
       4-[(6-chloropyridin-3-yl)methyl]-5,8-difluoro-N-[(1S,2S)-2-hydroxycyclohexyl]quinoline-2-carboxamide; 
       4-[(6-chloropyridin-3-yl)methyl]-8-fluoro-N-[(3R,4S)-3-hydroxytetrahydro-2H-pyran-4-yl]quinoline-2-carboxamide; 
       4-(4-chlorobenzyl)-8-fluoro-N-[(3R,4S)-3-hydroxytetrahydro-2H-pyran-4-yl]quinoline-2-carboxamide; 
       N-[(1S,2S)-2-hydroxycyclohexyl]-4-{[6-(pyrimidin-2-yl)pyridin-3-yl]methyl}quinoline-2-carboxamide; 
       N-[(1S,2S)-2-hydroxycyclohexyl]-4-{[6-(pyridazin-4-yl)pyridin-3-yl]methyl}quinoline-2-carboxamide; 
       N-[(1S,2S)-2-hydroxycyclohexyl]-4-{[6-(3-methoxypyrazin-2-yl)pyridin-3-yl]methyl}quinoline-2-carboxamide; 
       N-[(1S,2S)-2-hydroxycyclohexyl]-4-{[6-(1,3-thiazol-4-yl)pyridin-3-yl]methyl}quinoline-2-carboxamide; 
       N-[(1S,2S)-2-hydroxycyclohexyl]-4-[6′-methoxy-2,3′-bipyridin-5-yl)methyl]quinoline-2-carboxamide; 
       N-[(1S,2S)-2-hydroxycyclohexyl]-4-[2′-methoxy-2,3′-bipyridin-5-yl)methyl]quinoline-2-carboxamide; 
       N-[(1S,2S)-2-hydroxycyclohexyl]-4-[5′-methoxy-2,3′-bipyridin-5-yl)methyl]quinoline-2-carboxamide; 
       N-[(1S,2S)-2-hydroxycyclohexyl]-4-{[6-(1-methyl-1H-imidazol-2-yl)pyridin-3-yl]methyl}quinoline-2-carboxamide; 
       N-[(1S,2S)-2-hydroxycyclohexyl]-4-{[6-(1-methyl-1H-imidazol-2-yl)pyridin-3-yl]methyl}quinoline-2-carboxamide; 
       N-[(1S,2S)-2-hydroxycyclohexyl]-4-[(4′-methoxy-2,3′-bipyridin-5-yl)methyl]quinoline-2-carboxamide; 
       4-[(6-chloropyridin-3-yl)methyl]-5,8-difluoro-N-[(3R,4S)-3-hydroxytetrahydro-2H-pyran-4-yl]quinoline-2-carboxamide; 
       4-(4-chlorobenzyl)-5,8-difluoro-N-[(3R,4S)-3-hydroxytetrahydro-2H-pyran-4-yl]quinoline-2-carboxamide; 
       N-[(1S,2S)-2-hydroxycyclohexyl]-4-{[6-(methylsulfanyl)pyridin-3-yl]methyl}quinoline-2-carboxamide; 
       N-[(1S,2S)-2-hydroxycyclohexyl]-4-[(6-methoxypyridin-3-yl)methyl]quinoline-2-carboxamide; 
       N-[(1S,2S)-2-hydroxycyclohexyl]-4-{[6-(1,3-thiazol-2-yl)pyridin-3-yl]methyl}quinoline-2-carboxamide; 
       4-[(6-chloropyridin-3-yl)methyl]-7,8-difluoro-N-[(1S,2S)-2-hydroxycyclohexyl]quinoline-2-carboxamide; 
       4-[(6-chloropyridin-3-yl)methyl]-N-[(3R,4S)-3-hydroxytetrahydro-2H-pyran-4-yl]-8-(methylsulfanyl)quinoline-2-carboxamide; 
       N-[(3R,4S)-3-hydroxytetrahydro-2H-pyran-4-yl]-4-[4-(1-methyl-1H-pyrazol-4-yl)benzyl]quinoline-2-carboxamide; 
       N-[(3R,4S)-3-hydroxytetrahydro-2H-pyran-4-yl]-4-[4-(1-methyl-1H-pyrazol-5-yl)benzyl]quinoline-2-carboxamide; 
       N-[(3R,4S)-3-hydroxytetrahydro-2H-pyran-4-yl]-4-[(6-methoxypyridin-3-yl)methyl]quinoline-2-carboxamide; 
       N-[(3R,4S)-3-hydroxytetrahydro-2H-pyran-4-yl]-4-[(6)methoxypyridin-3-y-l)methyl]quinoline-2-carboxamide; 
       N-[(3R,4S)-3-hydroxytetrahydro-2H-pyran-4-yl]-4-[4-(1H-pyrazol-1-yl)benzyl]quinoline-2-carboxamide; 
       N-[(1S,2S)-2-hydroxycyclohexyl]-4-[(1-methyl-1H-benzotriazol-5-yl)methyl]quinoline-2-carboxamide; 
       4-[(6-chloropyridin-3-yl)methyl]-N-[(1S,2S)-2-hydroxycyclohexyl]quinoline-2-carboxamide 1-oxide; 
       4-(4-chlorobenzyl)-N-[(3R,4S)-3-hydroxytetrahydro-2H-pyran-4-yl]quinoline-2-carboxamide 1-oxide; 
       4-(4-cyanobenzyl)-N-[(3R,4S)-3-hydroxytetrahydro-2H-pyran-4-yl]quinoline-2-carboxamide; 
       N-[(1S,2S)-2-hydroxycyclohexyl]-4-(imidazo[1,2-a]pyridin-6-ylmethyl)quinoline-2-carboxamide; 
       N-[(1S,2S)-2-hydroxycyclohexyl]-4-([1,2,4]triazolo[1,5-a]pyridin-6-ylmethyl)quinoline-2-carboxamide; 
       N-[(1S,2S)-2-hydroxycyclohexyl]-4-[(5-methoxypyridin-3-yl)methyl]quinoline-2-carboxamide; 
       4-[fluoro(6-methoxypyridin-3-yl)methyl]-N-[(3R,4S)-3-hydroxytetrahydro-2H-pyran-4-yl]-8-methoxyquinoline-2-carboxamide; 
       4-(3,4-difluorobenzyl)-N-[(1S,2S)-2-hydroxycyclohexyl]quinoline-2-carboxamide; 
       4-(4-chloro-3-fluorobenzyl)-N-[(1S,2S)-2-hydroxycyclohexyl]quinoline-2-carboxamide; 
       8-fluoro-N-[(3R,4S)-3-hydroxytetrahydro-2H-pyran-4-yl]-4-[(6-methoxypyridin-3-yl)methyl]quinoline-2-carboxamide; 
       N-[(3R,4S)-3-hydroxytetrahydro-2H-pyran-4-yl]-4-{[6-(trifluoromethyl)pyridin-3-yl]methyl}quinoline-2-carboxamide; 
       N-[(1S,2S)-2-hydroxycyclohexyl]-4-[4-(5-methyl-1,2,4-oxadiazol-3-yl)benzyl]quinoline-2-carboxamide; 
       N-[(1S,2S)-2-hydroxycyclohexyl]-4-[4-(2-methyl-1,3-thiazol-4-yl)benzyl]quinoline-2-carboxamide; 
       N-[(1S,2S)-2-hydroxycyclohexyl]-4-[4-(3-methyl-1,2,4-oxadiazol-5-yl)benzyl]quinoline-2-carboxamide; 
       8-fluoro-N-[(3R,4S)-3-hydroxytetrahydro-2H-pyran-4-yl]-4-[4-(1-methyl-1H-pyrazol-4-yl)benzyl]quinoline-2-carboxamide; 
       N-[(1S,2S)-2-hydroxycyclohexyl]-4-[4-(pyrimidin-2-yl)benzyl]quinoline-2-carboxamide; 
       N-[(1S,2S)-2-hydroxycyclohexyl]-4-[4-(1-methyl-1H-pyrazol-3-yl)benzyl]quinoline-2-carboxamide; 
       N-[(1S,2S)-2-hydroxycyclohexyl]-4-[4-(1,3-thiazol-2-yl)benzyl]quinoline-2-carboxamide; 
       4-[(4-chlorophenyl)(fluoro)methyl]-N-[(3R,4S)-3-hydroxytetrahydro-2H-pyran-4-yl]quinoline-2-carboxamide; 
       N-[(1S,2S)-2-hydroxycyclohexyl]-4-(4-methoxybenzyl)-8-(1-methyl-1H-pyrazol-4-yl)quinoline-2-carboxamide; 
       4-[(6-chloropyridin-3-yl)methyl]-N-[(1S,2R)-2-hydroxycyclopentyl]quinoline-2-carboxamide; 
       4-[(6-chloropyridin-3-yl)methyl]-N-[(1S,2S)-2-hydroxycyclopentyl]quinoline-2-carboxamide; 
       4-[fluoro(6-methoxypyridin-3-yl)methyl]-N-[(3R,4S)-3-hydroxytetrahydro-2H-pyran-4-yl]quinoline-2-carboxamide; 
       8-chloro-N-[(3R,4S)-3-hydroxytetrahydro-2H-pyran-4-yl]-4-[(6-methoxypyridin-3-yl)methyl]quinoline-2-carboxamide; 
       8-fluoro-N-[(3R,4S)-3-hydroxytetrahydro-2H-pyran-4-yl]-4-{[6-(1-methyl-1H-pyrazol-4-yl)pyridin-3-yl]methyl}quinoline-2-carboxamide; 
       N-[(3S,4S)-4-hydroxytetrahydro-2H-pyran-3-yl]-4-[(6-methoxypyridin-3-yl)methyl]quinoline-2-carboxamide; 
       4-[(6-chloropyridin-3-yl)methyl]-8-fluoro-N-[(3S,4S)-4-hydroxytetrahydro-2H-pyran-3-yl]quinoline-2-carboxamide; 
       N-[(3R,4S)-3-hydroxytetrahydro-2H-pyran-4-yl]-4-{[6-(1-methyl-1H-pyrazol-4-yl)pyridin-3-yl]methyl}quinoline-2-carboxamide; 
       N-[(3R,4S)-4-hydroxytetrahydro-2H-pyran-4-yl]-4-{[6-(1-methyl-1H-pyrazol-3-yl)pyridin-3-yl]methyl}quinoline-2-carboxamide; 
       8-chloro-4-[(2-chloropyridin-4-yl)methyl]-N-[(3R,4S)-3-hydroxytetrahydro-2H-pyran-4-yl]quinoline-2-carboxamide; 
       4-{[6-(3-chloro-1-methyl-1H-pyrazol-4-yl)pyridin-3-yl]methyl}-N-[(1S,2S)-2-hydroxycyclohoexyl]quinoline-2-carboxamide; 
       8-chloro-N-[(1S,2S)-2-hydroxycyclohexyl]-4-{[6-(1-methyl-1H-pyrazol-4-yl)pyridin-3-yl]methyl}quinoline-2-carboxamide; 
       4-[(2-chloropyridin-4-yl)methyl]-N-[(3R,4S)-3-hydroxytetrahydro-2H-pyran-4-yl]quinoline-2-carboxamide; 
       4-[(2-chloropyridin-4-yl)carbonyl]-N-[(3R,4S)-3-hydroxytetrahydro-2H-pyran-4-yl]quinoline-2-carboxamide; 
       N-[(1S,2S)-2-hydroxycyclohexyl]-4-{[6-(1-methyl-1H-pyrazol-4-yl)-1-oxidopyridin-3-yl]methyl}quinoline-2-carboxamide; 
       4-[(2-chloropyridin-4-yl)methyl]-N-[(3S,4S)-4-hydroxytetrahydro-2H-pyran-3-yl]quinoline-2-carboxamide; quinoline-2-carboxamide; 
       N-[(3S,4S)-4-hydroxyheptan-3-yl]-4-{[2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl]methyl}quinoline-2-carboxamide; 
       8-fluoro-N-[(3R,4S)-3-hydroxytetrahydro-2H-pyran-4-yl]-4-[(6-methylpyridin-3-yl)methyl]quinoline-2-carboxamide 
       4-[(6-chloropyridin-3-yl)methyl]-N-cyclohexylquinoline-2-carboxamide; 
       4-[(2-chloropyridin-4-yl)methyl]-N-[(1S,2S)-2-hydroxycyclohexyl]quinoline-2-carboxamide; 
       5,8-difluoro-N-[(3R,4S)-3-hydroxytetrahydro-2H-pyran-4-yl]-4-[(6-methoxypyridin-3-yl)methyl]quinoline-2-carboxamide; 
       N-[(1S,2S)-2-hydroxycyclohexyl]-4-[(2-methylpyridin-4-yl)methyl]quinoline-2-carboxamide; 
       N-[(3S,4S)-4-hydroxyheptan-3-yl]-4-{[2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl]methyl}quinoline-2-carboxamide; 
       5,8-difluoro-N-[(3R,4S)-3-hydroxytetrahydro-2H-pyran-4-yl]-4-{[(6-(trifluoromethyl)pyridin-3-yl]methyl}quinoline-2-carboxamide; 
       N-[(1S,2S)-2-hydroxycyclohexyl]-4-(pyrazin-2-ylmethyl)quinoline-2-carboxamide; 
       N-[(3R,4S)-3-hydroxytetrahydro-2H-pyran-4-yl]-4-(pyrazin-2-ylmethyl)quinoline-2-carboxamide; 
       N-[(1S,2S)-2-hydroxycyclohexyl]-4-([(2-methoxypyridin-4-yl)methyl]quinoline-2-carboxamide; 
       N-[(3R,4S)-3-hydroxytetrahydro-2H-pyran-4-yl]-4-[(2-methoxypyridin-4-yl)methyl]quinoline-2-carboxamide; 
       4-{[6-(difluoromethyl)pyridin-3-yl]methyl}-8-fluoro-N-[(3R,4S)-3-hydroxytetrahydro-2H-pyran-4-yl]quinoline-2-carboxamide; 
       8-fluoro-N-[(3R,4S)-3-hydroxytetrahydro-2H-pyran-4-yl]-4-[(6-methoxy-1-oxidopyridin-3-yl)methyl]quinoline-2-carboxamide; 
       4-[(2-chloropyridin-4-yl)methyl]-8-fluoro-N-[(3R,4S)-3-hydroxytetrahydro-2H-pyran-4-yl]quinoline-2-carboxamide; 
       N-[(3R,4S)-3-hydroxytetrahydro-2H-pyran-4-yl]-4-[(2-methylpyridin-4-yl)methyl]quinoline-2-carboxamide; 
       N-[(1S,2S)-2-fluorocyclohexyl]-4-{[6-(1-methyl-1H-pyrazol-4-yl)pyridin-3-yl]methyl}quinoline-2-carboxamide; 
       N-[(1S,2S)-2-hydroxycyclohexyl]-4-{[2-(methylsulfanyl)pyrimidin-5-yl]methyl}quinoline-2-carboxamide; 
       4-[(6-chloropyridin-3-yl)methyl]-N-[(1S)-2-oxocyclohexyl]quinoline-2-carboxamide; 
       8-fluoro-N-[(3R,4S)-3-hydroxytetrahydro-2H-pyran-4-yl]-4-[(2-methoxypyridin-4-yl)methyl]quinoline-2-carboxamide; 
       N-[(3R,4S)-3-hydroxytetrahydro-2H-pyran-4-yl]-4-{[2-(methylsulfanyl)pyrimidin-5-yl]methyl}quinoline-2-carboxamide; 
       8-fluoro-4-[(6-hydroxypyridin-3-yl)methyl]-N-[(3R,4S)-3-hydroxytetrahydro-2H-pyran-4-yl]quinoline-2-carboxamide; 
       4-[(6-hydroxypyridin-3-yl)methyl]-N-[(3R,4S)-3-hydroxytetrahydro-2H-pyran-4-yl]quinoline-2-carboxamide; 
       4-[(2-hydroxypyridin-4-yl)methyl]-N-[(3R,4S)-3-hydroxytetrahydro-2H-pyran-4-yl]quinoline-2-carboxamide; 
       N-(2-methylcyclohexyl)-4-{[6-(1-methyl-1H-pyrazol-4-yl)pyridin-3-yl]methyl}quinoline-2-carboxamide; 
       8-fluoro-N-[(3R,4S)-3-hydroxytetrahydro-2H-pyran-4-yl]-4-[(2-methoxy-1-oxidopyridin-4-yl)methyl]quinoline-2-carboxamide; 
       8-fluoro-4-[(2-hydroxypyridin-4-yl)methyl]-N-[(3R,4S)-3-hydroxytetrahydro-2H-pyran-4-yl]quinoline-2-carboxamide; 
       4-{[6-(1-methyl-1H-pyrazol-4-yl)pyridin-3-yl]methyl}-N-[(1R,2S)-2-phenylcyclohexyl]quinoline-2-carboxamide; 
       N-[(1R,2R)-2-ethynylcyclohexyl]-4-{[6-(1-methyl-1H-pyrazol-4-yl)pyridin-3-yl]methyl}quinoline-2-carboxamide; 
       5,8-difluoro-N-[(3R,4S)-3-hydroxytetrahydro-2H-pyran-4-yl]-4-[(2-methoxypyridin-4-yl)methyl]quinoline-2-carboxamide; 
       N-[(1S,2S)-2-(hydroxymethyl)cyclohexyl]-4-{[6-(1-methyl-1H-pyrazol-4-yl)pyridin-3-yl]methyl}quinoline-2-carboxamide; 
       4-[(6-ethoxypyridin-3-yl)methyl]-N-[(3R,4S)-3-hydroxytetrahydro-2H-pyran-4-yl]quinoline-2-carboxamide; 
       N-[(3R,4S)-3-hydroxytetrahydro-2H-pyran-4-yl]-4-{[6-(2,2,2-trifluoroethoxy)pyridin-3-yl]methyl}quinoline-2-carboxamide; 
       N-[(3R,4S)-3-hydroxytetrahydro-2H-pyran-4-yl]-4-{[6-(tetrahydro-2H-pyran-4-yloxy)pyridin-3-yl]methyl}quinoline-2-carboxamide; 
       N-(2-methylidenecyclohexyl)-4-{[6-(1-methyl-1H-pyrazol-4-yl)pyridin-3-yl]methyl}quinoline-2-carboxamide; 
       N-[(3R,4S)-3-hydroxytetrahydro-2H-pyran-4-yl]-4-[(6-methoxy-1-oxidopyridin-3-yl)methyl]quinoline-2-carboxamide; 
       4-[(2-ethoxypyridin-4-yl)methyl]-N-[(3R,4S)-3-hydroxytetrahydro-2H-pyran-4-yl]quinoline-2-carboxamide; 
       8-fluoro-N-[(3R,4S)-3-hydroxytetrahydro-2H-pyran-4-yl]-4-{[6-(2,2,2-trifluoroethoxy)pyridin-3-yl]methyl}quinoline-2-carboxamide; 
       4-[(6-fluoropyridin-3-yl)methyl]-N-[(3R,4S)-3-hydroxytetrahydro-2H-pyran-4-yl]quinoline-2-carboxamide; 
       N-[(3R,4S)-3-hydroxytetrahydro-2H-pyran-4-yl]-4-{[6-(methylsulfanyl)pyridin-3-yl]methyl}quinoline-2-carboxamide; 
       4-[(2-ethoxypyridin-4-yl)methyl]-8-fluoro-N-[(3R,4S)-3-hydroxytetrahydro-2H-pyran-4-yl]quinoline-2-carboxamide; 
       4-[(6-ethoxypyridin-3-yl)methyl]-8-fluoro-N-[(3R,4S)-3-hydroxytetrahydro-2H-pyran-4-yl]quinoline-2-carboxamide; 
       N-[(3R,4S)-3-hydroxytetrahydro-2H-pyran-4-yl]-4-{[2-(methylsulfanyl)pyridin-4-yl]methyl}quinoline-2-carboxamide; 
       or a pharmaceutically acceptable salts thereof. 
     
     
         19 . A pharmaceutical composition comprising a therapeutically effective amount of a compound of  claims 1  or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier. 
     
     
         20 . A pharmaceutical composition for the treatment of a disease or disorder mediates by the muscarinic M1 receptor, wherein said disease or disorder is selected from the group consisting of Alzheimer's disease, schizophrenia, pain or sleep disorders, comprising a therapeutically effective amount of a compound of  claim 1  or a pharmaceutically acceptable salt there, and a pharmaceutically acceptable carrier. 
     
     
         21 . Use of a pharmaceutical composition of  claim 20  for the treatment of a disease or disorder mediated by the muscarinic M1 receptor, wherein said disease or disorder is selected from the group consisting of Alzheimer's disease, schizophrenia, pain or sleep disorders. 
     
     
         22 . Use of a compound of  claim 1  or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, for the manufacture of a medicament for the treatment of a disease or disorder mediated by the muscarinic M1 receptor, wherein said disease or disorder is selected from the group consisting of Alzheimer's disease, schizophrenia, pain or sleep disorders. 
     
     
         23 . A method of treating a disease or disorder mediated by the muscarinic M1 receptor, wherein said disease or disorder is selected from the group consisting of Alzheimer's disease, schizophrenia, pain or sleep disorders in a patient in need thereof, comprising administering to the patient a therapeutically effective amount of a compound of  claims 1  or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.