Heterocyclic fused cinnoline M1 receptor positive allosteric modulators

1. A compound of formula (I):

and pharmaceutically acceptable salts thereof, wherein

Q, V and Z are each selected from the group consisting of

1) —CH, and

2) N;

X and Y are linked together to form a fused ring moiety selected from the group consisting of

W is selected from the group consisting of

1) —CH, and

2) —N;

R 1 is optionally present at one or more of the ring carbon atoms, and is selected from the group consisting of

(1) —C 1-6 alkyl,

(2) —O—C 1-6 alkyl, or

(3) halogen;

R 2 is selected from the group consisting of

(1) aryl,

(2) 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,

(3) halogen,

wherein said aryl or heteroaryl is optionally substituted with one or more

(a) halogen,

(b) hydroxy,

(c)—O—C 1-6 alkyl,

(d)—C 1-6 alkyl,

(e) cyano,

(f) —NR A R B , wherein R A and R B are selected from the group consisting of

(i) hydrogen, or

(ii)—C 1-6 alkyl,

or R A and R B are linked together with the nitrogen to which they are both attached to form a 2-6 membered carbocyclic ring, wherein one or two of the ring carbon atoms is replaced by a nitrogen, oxygen or sulfur, and the carbocyclic is optionally substituted with one or more C 1-6 alkyl,

(g)—C(═O)—R C , wherein R C is selected from the group consisting of

(i) hydrogen, or

(ii) —C 1-6 alkyl, or

(h) —S(O) n —R C ;

R 3 is selected from the group consisting of

(1) aryl,

(2) 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,

(3)—C 5-10 cycloalkyl, or

(4) a heterocyclic group, which is a nonaromatic 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,

wherein said aryl, heteroaryl cycloalkyl or heterocyclic group is optionally substituted with one or more

(a) halogen,

(b) hydroxy,

(c) —O—C 1-6 alkyl, or

(d) —C 1-6 alkyl;

n is 0, 1 or 2.

2. A compound of claim 1 , wherein X and Y are linked together to form the fused ring moiety:

3. A compound of claim 1 , wherein X and Y are linked together to form the fused ring moiety:

4. A compound of 2 , wherein V, Q and Z are CH.

5. A compound of claim 2 , wherein V and Q are CH, and Z is N.

6. A compound of claim 1 , wherein R 2 is heteroaryl.

7. A compound of claim 1 , wherein R 2 is aryl.

8. A compound of claim 1 , wherein R 3 is aryl.

9. A compound of claim 1 , wherein R 3 is heteroaryl.

10. A compound of claim 1 , wherein R 3 is cycloalkyl.

11. A compound of claim 1 , wherein R 3 is heterocyclic.

12. A compound of claim 1 , wherein the compound of formula (I) is a compound of formula (II):

and pharmaceutically acceptable salts thereof, wherein V, Q, Z, R 1 , R 2 and R 3 are as previously defined.

13. A compound of claim 12 , wherein the compound of formula (II) is a compound of formula (IIA)

wherein R 2 is selected from the group consisting of

or a pharmaceutically acceptable salt thereof.

14. A compound of claim 12 , wherein the compound of formula (II) is a compound of formula (IIB)

wherein R 3 is selected from the group consisting of

or a pharmaceutically acceptable salt thereof.

15. A compound of claim 12 , wherein the compound of formula (II) is a compound of formula (IIC)

wherein R 2 is selected from the group consisting of

16. A compound of claim 1 , wherein the compound of formula (I) is a compound of formula (III):

and pharmaceutically acceptable salts thereof, wherein V, Q, Z, R 1 , R 2 and R 3 are defined in claim 1 .

17. A compound of claim 16 , wherein the compound of formula (III) is a compound of formula (IIIA)

wherein R 3 is selected from the group consisting of

or a pharmaceutically acceptable salt thereof.

18. A compound which is selected from the group consisting of

2-(2,3-Dimethylphenyl)-5 -{[6-(1-methyl-1H-pyrazol-4-yl)pyridin-3-yl]methyl} -2,5-dihydro -3H-pyrazolo[4,3-c]pyrido[3,2-e]pyridazin-3-one;

5-[(6-Chloropyridin-3-yl)methyl]-2-(2,3-dimethylphenyl)-2,5-dihydro-3H-pyrazolo[4,3-c ]pyrido[3,2-e]pyridazin-3-one;

2-(2,3-Dimethylphenyl)-5-[(6′-methyl-2,3′-bipyridin-5-yl)methyl]-2,5-dihydro-3H-pyrazolo [4,3-c]pyrido[3,2-e]pyridazin-3-one;

2-(2-Fluoro-3-methylphenyl)-5-[(6′-methyl-2,3′-bipyridin-5-yl)methyl]-2,5-dihydro-3H-pyrazolo [4,3-c]pyrido[3,2-e]pyridazin-3-one;

(±)-2-(trans-2-Hydroxycyclohexyl)-5-[(6′-methyl-2,3′-bipyridin-5-yl)methyl]-2,5-dihydro -3H-pyrazolo[4,3-c]pyrido[3,2-e]pyridazin-3-one;

(±)-5-[(6′-Methyl-2,3′-bipyridin-5-yl)methyl]-2-(tetrahydro-2H-pyran-3-yl)-2,5-dihydro-3 H-pyrazolo[4,3-c]pyrido[3,2-e]pyridazin-3-one;

(±)-5-{[4-(1H-Pyrazol-1 -yl)phenyl]methyl}-2-(tetrahydro-2H-pyran-3-yl)-2,5 -dihydro-3H-pyrazolo[4,3-c]pyrido[3,2-e]pyridazin-3-one;

(±)-5-{[4-(6-Methylpyridin-3-yl)phenyl]methyl}-2-(tetrahydro-2H-pyran-3 -yl)-2,5 -dihydro -3H-pyrazolo[4,3-c]pyrido[3,2-e]pyridazin-3-one;

(±)-2-(Tetrahydro-2H-pyran-3 -yl)-5 -{[4-(1 ,3-thiazol-4-yl)phenyl]methyl}-2,5-dihydro-3H-pyrazolo[4,3-c]pyrido[3,2-e]pyridazin-3-one;

(±)-5-{[4-(6-Hydroxypyridin-3-yl)phenyl]methyl}-2-(tetrahydro-2H-pyran-3 -yl)-2,5 -dihydro -3H-pyrazolo[4,3-c]pyrido[3,2-e]pyridazin-3-one;

2-(2-Methylphenyl)-5 - {[4-(1H-pyrazol-1-yl)phenyl]methyl}-2,5 -dihydro-3H-pyrazolo [4,3-c]thieno[2,3-e]pyridazin-3-one;

(±)-5- {[4-(1H-Pyrazol-1-yl)phenyl]methyl}-2-(tetrahydro-2H-pyran-3 -yl)-2,5 -dihydro-3H-pyrazolo[4,3-c]thieno[2,3-e]pyridazin-3-one;

(±)-5- {[4-(6-Methylpyridin-3-yl)phenyl]methyl}-2-(tetrahydro-2H-pyran-3 -yl)-2,5 -dihydro -3H-pyrazolo[4,3-c]thieno[2,3-e]pyridazin-3-one;

(±)-5- {[4-(2-Methylpyridin-4-yl)phenyl]methyl}-2-(tetrahydro-2H-pyran-3 -yl)-2,5 -dihydro -3H-pyrazolo[4,3-c]thieno[2,3-e]pyridazin-3-one;

or a pharmaceutically acceptable salt thereof.

19. 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.