Naphthalene carboxamide M1 receptor positive allosteric modulators

1. Compound of formula (I):

wherein

R 1 is selected from the group consisting of

(1) hydrogen,

(2) —R 3 ,

(3) —C 1-6 alkyl,

(4) —C 2-6 alkenyl, and

(5) —C(O)N(R 4 ) 2 ,

wherein each is optionally substituted with one or more R a ;

R 2 is selected from the group consisting of

(1) hydroxyl, and

(2) —N(R 4 ) 2 ,

wherein each is optionally substituted with one or more R a ;

R 3 and R 4 are independently selected from the group consisting of

(1) hydrogen,

(2) hydroxyl,

(3) —C 1-6 alkyl,

(4) —C 3-10 cycloalkyl, and

(5) —C 5-10 heterocyclyl,

wherein each is optionally substituted with one or more R a ;

A is selected from the group consisting of

(1) —C 6-10 aryl, and

(2) —C 6-10 heteroaryl,

wherein each is optionally substituted with one or more R a ;

R a is selected from the group consisting of

(1) hydrogen,

(2) hydroxyl,

(3) halogen,

(4) —O,

(5) —C 1-6 alkyl,

(6) —C 3-10 cycloalkyl, which is unsubstituted or substituted with one or more hydroxyl,

(7) —C 5-10 heteroaryl, which is unsubstituted or substituted with one or more hydroxyl,

(8) —CN,

(9) —OR 3 ,

(10) —SR 3 ,

(11) —N(R 4 ) n , and

(12) —C(O)R 3 O(C)O;

n is independently 1 to 4;

or a pharmaceutically acceptable salt thereof, provided R 1 is not hydrogen when A is phenyl and R 2 is hydroxyl.

2. A compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 1 is selected from the group consisting of

(1) hydrogen,

(2) methyl,

(3) ethyl,

(4) ethylenyl, and

(5) C(O)NHCH 2 CH 3 .

3. A compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 2 is N(R 4 ) 2 and each R 4 is independently selected from the group consisting of

(1) hydrogen,

(2) —C 3-10 cycloalkyl, and

(3) —C 5-10 heterocyclyl,

wherein said cycloalkyl and said heterocyclyl are optionally substituted with one or more R a .

4. A compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein A is selected from the group consisting of

(1) phenyl,

(2) pyridyl,

(3) piperazinyl,

(4) biphenyl, and

(5) bipyridyl

wherein said cycloalkyl and said heterocyclic are optionally substituted with one or more R a .

5. A compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein R 1 is hydrogen.

6. A compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein R 1 is methyl.

7. A compound of claim 1 or a pharmaceutically acceptable salt thereof, where R 2 is hydroxyl.

8. A compound of claim 1 or a pharmaceutically acceptable salt thereof, where R 2 is N(R 4 ) 2 and R 4 is hydrogen and C 3-10 cycloalkyl, which is optionally substituted with one or more R a .

9. A compound of claim 1 or a pharmaceutically acceptable salt thereof, where R 2 is N(R 4 ) 2 and R 4 is hydrogen and cyclohexyl, which is optionally substituted with one or more R a .

10. A compound of claim 1 or a pharmaceutically acceptable salt thereof, where R 2 is N(R 4 ) 2 and R 4 is hydrogen and cyclohexyl, which is optionally substituted with one or more hydroxyl.

11. A compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein R 3 is —C 1-6 alkyl.

12. A compound of claim 1 , which is selected from the group consisting of

1-Methoxy-4-(4-methoxybenzyl)-2-naphthoic acid;

1-Methoxy-4-[4-(1H-pyrazol-1-yl)benzyl]-2-naphthoic acid;

4-[(6-Chloropyridin-3-yl)methyl]-N-[(1S,2S)-2-hydroxycyclohexyl]-1-methoxy-2-naphthamide;

N-[(1S,2S)-2-Hydroxycyclohexyl]-1-methoxy-4-[(6-methylpyridin-3-yl)methyl-2-naphthamide;

N-[(1S,2S)-2-Hydroxycyclohexyl]-1-methoxy-4-{[6-(1-methyl-1H-pyrazol-4-yl)pyridine-3-yl]methyl}-2-naphthamide;

1-Hydroxy-N-[(1S,2S)-2-hydroxycyclohexyl]-4-{[6-(1H-pyrazol-1-yl)pyridine-3-yl]methyl}-2-naphthamide;

N-[(1S,2S)-2-Hydroxycyclohexyl]-1-methoxy-4-{[6-(1H-pyrazol-1-yl)pyridine-3-yl]methyl}-2-naphthamide;

N-[(1S,2S)-2-Hydroxycyclohexyl]-1-methoxy-4-{[4-(1-methyl-1H-pyrazol-4-yl)piperazin-1-yl]methyl}-2-naphthamide;

N-[(1S,2S)-2-Hydroxycyclohexyl]-1-methoxy-4-[(6-vinylpyridin-3-yl)methyl]-2-naphthamide;

4-[(6-Chloropyridin-3-yl)methyl]-N-[(3R,4S)-3-hydroxytetrahydro-2H-pyran-4-yl]-1-methoxy-2-naphthamide;

N-[(1S,2S)-2-Hydroxycyclohexyl]-1-methoxy-4-{[2-(methylthio)pyridin-4-yl]methyl}-2-naphthamide; and

4-[(6-Chloropyridin-3-yl)methyl]-1-ethoxy-N-(1S,2S)-2-hydroxycyclohexyl]-2-naphthamide

or a pharmaceutically acceptable salt thereof.

13. A compound of claim 1 represented by structural formula (II):

or a pharmaceutically acceptable salt thereof, wherein R 1 and A are as defined in claim 1 .

14. A compound of claim 13 , or a pharmaceutically acceptable salt thereof, wherein R 1 is selected from the group consisting of

(1) hydrogen,

(2) methyl,

(3) ethyl,

(4) —C 2-6 alkenyl, and

(5) —C(O)N(R 4 ) 2 ,

wherein each is optionally substituted with one or more R a .

15. A compound of claim 14 , or a pharmaceutically acceptable salt thereof, wherein A is selected from the group consisting of

(1) phenyl,

(2) pyridyl,

(3) piperazinyl,

(4) biphenyl, and

(5) bipyridyl.

16. A compound of claim 14 , or a pharmaceutically acceptable salt thereof, wherein A is

17. A pharmaceutical composition comprising a therapeutically effective amount of a compound of claim 1 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

18. 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 and sleep disorders in a patient in need thereof, comprising administering to the patient a therapeutically effective amount of a compound of claim 1 or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.