Imidazo[4,5-c]quinoline and imidazo[4,5-c][1,5]naphthyridine derivatives as LRRK2 inhibitors

1. A compound of Formula (I)

or a pharmaceutically acceptable salt thereof; wherein

X is CR 7 or N;

Z is CR 3 or N;

R 1 is selected from the group consisting of cyano and a 5- to 10-membered heteroaryl which contains 1 to 5 heteroatoms independently selected from N, O and S; wherein the 5- to 10-membered heteroaryl is optionally substituted with 1 to 3 R 8 ;

R 1a and R 1b are each independently hydrogen, halo, hydroxy or C 1 -C 3 alkyl;

R 2 is a C 3 -C 7 cycloalkyl or a 4- to 7-membered heterocycloalkyl which contains 1 to 3 heteroatoms independently selected from NR, O and S; wherein the C 3 -C 7 cycloalkyl and 4- to 7-membered heterocycloalkyl are each optionally substituted with 1 to 3 R 9 ; and wherein the C 1 -C 6 alkyl is optionally substituted with 1 to 3 R 10 ;

R is hydrogen, C 1 -C 6 alkyl or absent;

R 3 , R 4 , R 5 , R 6 and R 7 are each independently selected from the group consisting of hydrogen, deutero, amino, halo, hydroxy, cyano, C 1 -C 6 alkyl, C 3 -C 6 cycloalkyl and C 1 -C 6 alkoxy; wherein the C 1 -C 6 alkyl, C 3 -C 6 cycloalkyl and C 1 -C 6 alkoxy are each optionally substituted with 1 to 3 halo or C 1 -C 3 alkoxy;

R 8 at each occurrence is independently selected from the group consisting of halo, —C(O)NH 2 , —C(O)NH(C 1 -C 3 alkyl), —C(O)N(C 1 -C 3 alkyl) 2 , C 1 -C 6 alkyl, C 1 -C 6 alkoxy and C 3 -C 6 cycloalkyl; wherein the C 1 -C 6 alkyl, C 1 -C 6 alkoxy and C 3 -C 6 cycloalkyl are each optionally substituted with 1 to 3 halo, cyano, hydroxy or C 1 -C 3 alkoxy;

R 9 at each occurrence is independently selected from the group consisting of halo, hydroxy, C 1 -C 6 alkyl, C 1 -C 6 alkoxy, and C 1 -C 6 alkoxyC 1 -C 6 alkyl, wherein the C 1 -C 6 alkyl, C 1 -C 6 alkoxy, and C 1 -C 6 alkoxyC 1 -C 6 alkyl are optionally substituted with one to three halo or a cyano; and

R 10 at each occurrence is independently selected from the group consisting of halo, C 1 -C 6 alkoxy, C 1 -C 6 thioalkoxy, amino, C 1 -C 6 alkylamino and di(C 1 -C 6 alkyl)amino.

2. A compound of Formula (I)

or a pharmaceutically acceptable salt thereof; wherein

X is CR 7 or N;

Z is CR 3 or N;

R 1 is selected from the group consisting of cyano and a 5- to 10-membered heteroaryl which contains 1 to 5 heteroatoms independently selected from N, O and S; wherein the 5- to 10-membered heteroaryl is optionally substituted with 1 to 3 R 8 ;

R 1a and R 1b are each independently hydrogen, halo, hydroxy or C 1 -C 3 alkyl;

R 2 is a C 3 -C 7 cycloalkyl or a 4- to 7-membered heterocycloalkyl which contains 1 to 3 heteroatoms independently selected from NR, O and S; wherein the C 3 -C 7 cycloalkyl and 4- to 7-membered heterocycloalkyl are each optionally substituted with 1 to 3 R 9 ; and wherein the C 1 -C 6 alkyl is optionally substituted with 1 to 3 R 10 ;

R is hydrogen, C 1 -C 6 alkyl or absent;

R 3 , R 4 , R 5 , R 6 and R 7 are each independently selected from the group consisting of hydrogen, deutero, amino, halo, hydroxy, cyano, C 1 -C 6 alkyl, C 3 -C 6 cycloalkyl and C 1 -C 6 alkoxy; wherein the C 1 -C 6 alkyl, C 3 -C 6 cycloalkyl and C 1 -C 6 alkoxy are each optionally substituted with 1 to 3 halo or C 1 -C 3 alkoxy;

R 8 at each occurrence is independently selected from the group consisting of halo, —C(O)NH 2 , —C(O)NH(C 1 -C 3 alkyl), —C(O)N(C 1 -C 3 alkyl) 2 , C 1 -C 6 alkyl, C 1 -C 6 alkoxy and C 3 -C 6 cycloalkyl; wherein the C 1 -C 6 alkyl, C 1 -C 6 alkoxy and C 3 -C 6 cycloalkyl are each optionally substituted with 1 to 3 halo, cyano, hydroxy or C 1 -C 3 alkoxy;

R 9 at each occurrence is independently selected from the group consisting of halo, hydroxy, C 1 -C 6 alkyl, C 1 -C 6 alkoxy, and C 1 -C 6 alkoxyC 1 -C 6 alkyl, wherein the C 1 -C 6 alkyl, C 1 -C 6 alkoxy, and C 1 -C 6 alkoxyC 1 -C 6 alkyl are optionally substituted with one to three halo or a cyano; and

R 10 at each occurrence is independently selected from the group consisting of halo, C 1 -C 6 alkoxy, C 1 -C 6 thioalkoxy, amino, C 1 -C 6 alkylamino and di(C 1 -C 6 alkyl)amino.

3. The compound of claim 2 or a pharmaceutically acceptable salt thereof wherein

X is CR 7 ;

Z is CR 3 ;

R 3 is hydrogen, bromo, chloro, fluoro, methoxy or cyano; and

R 4 , R 5 , R 6 and R 7 are each hydrogen or deutero.

4. The compound of claim 3 or a pharmaceutically acceptable salt thereof wherein

R 1 is a 5- to 10-membered heteroaryl which contains 1 to 4 heteroatoms independently selected from N, O and S; wherein the 5- to 10-membered heteroaryl is optionally substituted with 1 to 2 R 8 ;

R 1a and R 1b are each hydrogen; and

R 8 at each occurrence is independently selected from the group consisting of halo, C 1 -C 3 alkyl, C 1 -C 3 alkoxy and C 3 -C 6 cycloalkyl; wherein the C 1 -C 3 alkyl is optionally substituted with 1 to 3 fluoro, hydroxy or C 1 -C 3 alkoxy.

5. The compound of claim 4 or a pharmaceutically acceptable salt thereof wherein

R 1 is a 5- to 10-membered heteroaryl selected from the group consisting of oxazolyl, isoxazolyl, oxadiazolyl, thiazolyl, pyrazolyl, triazolyl, tetrazolyl, pyridinyl, benzoxazolyl, benzoisoxazolyl, benzopyrazolyl, benzotriazolyl, imidazothiazolyl and imidazothiadiazolyl; each of which is optionally substituted with an R 8 ; and R 8 is selected from the group consisting of methyl, trifluoromethyl, isopropyl, 2-hydroxyisopropyl, methoxy, methoxymethyl, cyclopropyl and chloro.

6. The compound of claim 5 or a pharmaceutically acceptable salt thereof wherein R 1 is selected from the group consisting of

7. The compound of claim 5 or a pharmaceutically acceptable salt thereof wherein R 1 is selected from the group consisting of

8. The compound of claim 5 or a pharmaceutically acceptable salt thereof wherein R 2 is tetrahydropyranyl, cyclopentyl or cyclohexyl; each of which is optionally substituted with 1 to 2 R 9 ; and

R 9 at each occurrence is independently methyl, ethyl, cyanomethyl, hydroxy or fluoro.

9. The compound of claim 8 or a pharmaceutically acceptable salt thereof wherein

R 2 is selected from the group consisting of

10. The compound of claim 9 or a pharmaceutically acceptable salt thereof wherein R 2 is

11. The compound of claim 8 or a pharmaceutically acceptable salt thereof wherein R 2 is selected from the group consisting of

12. The compound of claim 2 or a pharmaceutically acceptable salt thereof wherein

X is N;

Z is CR 3 ;

R 1 is a 5- to 10-membered heteroaryl selected from the group consisting of oxazolyl, isoxazolyl, oxadiazolyl, thiazolyl, pyrazolyl, triazolyl, tetrazolyl, pyridinyl, benzoxazolyl, benzoisoxazolyl, benzopyrazolyl, benzotriazolyl, imidazothiazolyl and imidazothiadiazolyl; each of which is optionally substituted with an R 8 ;

R 1a and R 1b are each hydrogen; and

R 8 is methyl, trifluoromethyl, isopropyl, 2-hydroxyisopropyl, methoxy, methoxymethyl, cyclopropyl or chloro.

13. The compound of claim 12 or a pharmaceutically acceptable salt thereof wherein

R 2 is

and

R 3 , R 4 , R 5 and R 6 are each hydrogen or deutero.

14. The compound of claim 2 or a pharmaceutically acceptable salt thereof wherein

X is CR 7 ;

Z is CR 3 ;

R 1 is cyano;

R 1a and R 1b are each hydrogen;

R 2 is tetrahydropyranyl or cyclopentyl; each of which is optionally substituted with 1 to 2 R 9 ; and

R 9 at each occurrence is independently methyl, cyanomethyl or fluoro.

15. The compound of claim 14 or a pharmaceutically acceptable salt thereof wherein

R 2 is

R 3 is hydrogen, bromo, chloro, methoxy or cyano; and

R 4 , R 5 , R 6 and R 7 are each hydrogen or deutero.

16. A compound selected from the group consisting of

8-methoxy-2-[(5-methyl-1,2-oxazol-3-yl)methyl]-1-[(2R,4R)-2-methyltetrahydro-2H-pyran-4-yl]-1H-imidazo[4,5-c]quinoline;

8-methoxy-2-[(5-methyl-1,2-oxazol-3-yl)methyl]-1-[(2S,4S)-2-methyltetrahydro-2H-pyran-4-yl]-1H-imidazo[4,5-c]quinoline;

8-chloro-2-[(5-methoxypyridin-2-yl)methyl]-1-[(2R,4R)-2-methyltetrahydro-2H-pyran-4-yl]-1H-imidazo[4,5-c]quinoline;

2-[(5-methyl-1,2-oxazol-3-yl)methyl]-1-[(2R,4R)-2-methyltetrahydro-2H-pyran-4-yl]-1H-imidazo[4,5-c]quinoline-8-carbonitrile;

8-chloro-2-[(5-methyl-1,2-oxazol-3-yl)methyl]-1-[(2R,4R)-2-methyltetrahydro-2H-pyran-4-yl]-1H-imidazo[4,5-c]quinoline;

8-chloro-2-[(5-methyl-1,2,4-oxadiazol-3-yl)methyl]-1-[(2R,4R)-2-methyltetrahydro-2H-pyran-4-yl]-1H-imidazo[4,5-c]quinoline;

8-bromo-1-[(1 S,3R)-3-fluorocyclopentyl]-2-methyl-1H-imidazo[4,5-c]quinoline;

1-[(2R,4R)-2-methyltetrahydro-2H-pyran-4-yl]-2-(1,3-thiazol-4-ylmethyl)-1H-imidazo[4,5-c][1,5]naphthyridine;

1-[(2S,4S)-2-methyltetrahydro-2H-pyran-4-yl]-2-(1,3-thiazol-4-ylmethyl)-1H-imidazo[4,5-c][1,5]naphthyridine;

8-chloro-2-(imidazo[2,1-b][1,3,4]thiadiazol-6-ylmethyl)-1-[(2R,4R)-2-methyltetrahydro-2H-pyran-4-yl]-1H-imidazo[4,5-c]quinoline;

{8-chloro-1-[(2R,4R)-2-methyltetrahydro-2H-pyran-4-yl]-1H-imidazo[4,5-c]quinolin-2-yl}acetonitrile;

8-chloro-1-[(2R,4R)-2-methyltetrahydro-2H-pyran-4-yl]-2-(1,3-thiazol-4-ylmethyl)(4- 2 H)-1H-imidazo[4,5-c]quinoline;

8-chloro-1-[(2R,4R)-2-methyltetrahydro-2H-pyran-4-yl]-2-[(4-methyl-1H-1,2,3-triazol-1-yl)methyl]-1H-imidazo[4,5-c]quinoline;

8-bromo-1-[(2R,4R)-2-methyltetrahydro-2H-pyran-4-yl]-2-(1,2-oxazol-3-ylmethyl)-1H-imidazo[4,5-c]quinoline;

8-chloro-1-[(2R,4R)-2-methyltetrahydro-2H-pyran-4-yl]-2-(1,2,4-oxadiazol-3-ylmethyl)-1H-imidazo[4,5-c]quinoline;

2-methyl-1-(tetrahydro-2H-pyran-4-yl)-1H-imidazo[4,5-c]quinoline-8-carbonitrile;

2-methyl-1-(cis-2-methyltetrahydro-2H-pyran-4-yl)-1H-imidazo[4,5-c]quinoline;

1-[(1R,3S)-3-fluorocyclopentyl]-2-(1,2-oxazol-3-ylmethyl)-1H-imidazo[4,5-c]quinoline;

8-chloro-2-methyl-1-(tetrahydro-2H-pyran-4-yl)-1H-imidazo[4,5-c]quinoline;

2-(1,2-oxazol-3-ylmethyl)-1-(tetrahydro-2H-pyran-4-yl)-1H-imidazo[4,5-c]quinoline;

2-methyl-1-(cis-2-methyltetrahydro-2H-pyran-4-yl)-1H-imidazo[4,5-c]quinoline-8-carbonitrile;

1-[(1 S,3R)-3-fluorocyclopentyl]-2-methyl-1H-imidazo[4,5-c]quinoline-8-carbonitrile;

1-(cis-2-methyltetrahydro-2H-pyran-4-yl)-2-(1,2-oxazol-3-ylmethyl)-1H-imidazo[4,5-c]quinoline-8-carbonitrile;

1-[(2R,4R)-2-methyltetrahydro-2H-pyran-4-yl]-2-(1,2-oxazol-3-ylmethyl)-1H-imidazo[4,5-c]quinoline-8-carbonitrile;

1-(trans-2-methyltetrahydro-2H-pyran-4-yl)-2-(1,2-oxazol-3-ylmethyl)-1H-imidazo[4,5-c]quinoline-8-carbonitrile;

1-[(2S,4R)-2-methyltetrahydro-2H-pyran-4-yl]-2-(1,2-oxazol-3-ylmethyl)-1H-imidazo[4,5-c]quinoline-8-carbonitrile;

8-bromo-1-[(1 S,3R)-3-fluorocyclopentyl]-2-(1,2-oxazol-3-ylmethyl)-1H-imidazo[4,5-c]quinoline;

1-[(1R,3S)-3-fluorocyclopentyl]-2-(1H-1,2,4-triazol-1-ylmethyl)-1H-imidazo[4,5-c]quinoline;

1-[(1R,3S)-3-fluorocyclopentyl]-2-[(4-methyl-1H-1,2,3-triazol-1-yl)methyl]-1H-imidazo[4,5-c]quinoline;

2-(1,3-benzoxazol-2-ylmethyl)-1-[(1R,3S)-3-fluorocyclopentyl]-1H-imidazo[4,5-c]quinoline;

2-(1,2-benzoxazol-3-ylmethyl)-1-(tetrahydro-2H-pyran-4-yl)-1H-imidazo[4,5-c]quinoline;

1-(tetrahydro-2H-pyran-4-yl)-2-(1H-1,2,4-triazol-1-ylmethyl)-1H-imidazo[4,5-c]quinoline;

2-[(2-methylimidazo[2,1-b][1,3]thiazol-6-yl)methyl]-1-(tetrahydro-2H-pyran-4-yl)-1H-imidazo[4,5-c]quinoline;

2-[(4-methyl-1H-1,2,3-triazol-1-yl)methyl]-1-(tetrahydro-2H-pyran-4-yl)-1H-imidazo[4,5-c]quinoline;

2-{[4-(methoxymethyl)-1H-1,2,3-triazol-1-yl]methyl}-1-(tetrahydro-2H-pyran-4-yl)-1H-imidazo[4,5-c]quinoline;

2-(1,3-benzoxazol-2-ylmethyl)-1-(tetrahydro-2H-pyran-4-yl)-1H-imidazo[4,5-c]quinoline;

1-(tetrahydro-2H-pyran-4-yl)-2-(1H-tetrazol-1-ylmethyl)-1H-imidazo[4,5-c]quinoline;

1-(tetrahydro-2H-pyran-4-yl)-2-(1,3-thiazol-4-ylmethyl)-1H-imidazo[4,5-c]quinoline;

2-[(5-methoxypyridin-2-yl)methyl]-1-(tetrahydro-2H-pyran-4-yl)-1H-imidazo[4,5-c]quinoline;

2-[(2-methylimidazo[2,1-b][1,3,4]thiadiazol-6-yl)methyl]-1-(tetrahydro-2H-pyran-4-yl)-1H-imidazo[4,5-c]quinoline;

2-[(5-methyl-1,2-oxazol-3-yl)methyl]-1-(tetrahydro-2H-pyran-4-yl)-1H-imidazo[4,5-c]quinoline;

2-(1-{[1-(tetrahydro-2H-pyran-4-yl)-1H-imidazo[4,5-c]quinolin-2-yl]methyl}-1H-1,2,3-triazol-4-yl)propan-2-ol;

2-(1H-benzotriazol-1-ylmethyl)-1-(tetrahydro-2H-pyran-4-yl)-1H-imidazo[4,5-c]quinoline;

2-[(4-cyclopropyl-1H-1,2,3-triazol-1-yl)methyl]-1-(tetrahydro-2H-pyran-4-yl)-1H-imidazo[4,5-c]quinoline;

1-(tetrahydro-2H-pyran-4-yl)-2-{[4-(trifluoromethyl)-1H-pyrazol-1-yl]methyl}-1H-imidazo[4,5-c]quinoline;

2-{[4-(propan-2-yl)-1H-1,2,3-triazol-1-yl]methyl}-1-(tetrahydro-2H-pyran-4-yl)-1H-imidazo[4,5-c]quinoline;

2-(2H-indazol-2-ylmethyl)-1-(tetrahydro-2H-pyran-4-yl)-1H-imidazo[4,5-c]quinoline;

1-(2,2-difluorocyclohexyl)-2-(1,2-oxazol-3-ylmethyl)-1H-imidazo[4,5-c]quinoline;

1-(2,2-dimethyltetrahydro-2H-pyran-4-yl)-2-(1,2-oxazol-3-ylmethyl)-1H-imidazo[4,5-c]quinoline;

1-(4,4-difluorocyclohexyl)-2-(1,2-oxazol-3-ylmethyl)-1H-imidazo[4,5-c]quinoline;

trans-3-[2-(1,2-oxazol-3-ylmethyl)-1H-imidazo[4,5-c]quinolin-1-yl]cyclohexanol;

1-cyclohexyl-2-(1,2-oxazol-3-ylmethyl)-1H-imidazo[4,5-c]quinoline;

8-chloro-2-[(5-methyl-1,2,4-oxadiazol-3-yl)methyl]-1-[(2S,4S)-2-methyltetrahydro-2H-pyran-4-yl]-1H-imidazo[4,5-c]quinoline;

8-chloro-1-[(2R,4R)-2-methyltetrahydro-2H-pyran-4-yl]-2-(1,2-oxazol-3-ylmethyl)-1H-imidazo[4,5-c]quinoline;

8-chloro-1-[(2R,4R)-2-methyltetrahydro-2H-pyran-4-yl]-2-(1,3-thiazol-4-ylmethyl)-1H-imidazo[4,5-c]quinoline;

8-fluoro-1-[(2R,4R)-2-methyltetrahydro-2H-pyran-4-yl]-2-(1,2-oxazol-3-ylmethyl)-1H-imidazo[4,5-c]quinoline;

8-fluoro-1-[(2R,4R)-2-methyltetrahydro-2H-pyran-4-yl]-2-(1,3-thiazol-4-ylmethyl)-1 H-imidazo[4,5-c]quinoline;

8-bromo-1-(cis-2-methyltetrahydro-2H-pyran-4-yl)-2-(1,3-thiazol-4-ylmethyl)-1H-imidazo[4,5-c]quinoline;

1-[(2R,4R)-2-methyltetrahydro-2H-pyran-4-yl]-2-(1,3-thiazol-4-ylmethyl)-1H-imidazo[4,5-c]quinoline-8-carbonitrile;

8-bromo-2-[(5-methyl-1,2-oxazol-3-yl)methyl]-1-(cis-2-methyltetrahydro-2H-pyran-4-yl)-1H-imidazo[4,5-c]quinoline;

8-bromo-1-[(2R,4r,6S)-2,6-dimethyltetrahydro-2H-pyran-4-yl]-2-(1,2-oxazol-3-ylmethyl)-1H-imidazo[4,5-c]quinoline;

8-bromo-1-[(2R,4r,6S)-2,6-dimethyltetrahydro-2H-pyran-4-yl]-2-(1,2-oxazol-3-ylmethyl)-1H-imidazo[4,5-c]quinoline;

8-bromo-1-[(-[(2R,4r,6S)-2,6-dimethyltetrahydro-2H-pyran-4-yl]-2-(1,3-thiazol-4-ylmethyl)-1H-imidazo[4,5-c]quinoline;

1-[(2R,4r,6S)-2,6-dimethyltetrahydro-2H-pyran-4-yl]-2-(1,3-thiazol-4-ylmethyl)-1H-imidazo[4,5-c]quinoline-8-carbonitrile;

8-methoxy-1-[(2R,4R)-2-methyltetrahydro-2H-pyran-4-yl]-2-(1,2-oxazol-3-ylmethyl)-1H-imidazo[4,5-c]quinoline;

8-chloro-2-(1,2-oxazol-3-ylmethyl)-1-(tetrahydro-2H-pyran-4-yl)-1H-imidazo[4,5-c]quinoline;

8-chloro-2-(imidazo[2,1-b][1,3,4]thiadiazol-6-ylmethyl)-1-[(2S,4S)-2-methyltetrahydro-2H-pyran-4-yl]-1H-imidazo[4,5-c]quinoline;

8-chloro-1-[(2R,4R)-2-methyltetrahydro-2H-pyran-4-yl]-2-(1H-1,2,4-triazol-1-ylmethyl)-1H-imidazo[4,5-c]quinoline;

8-bromo-1-(cis-2-ethyltetrahydro-2H-pyran-4-yl)-2-(1,2-oxazol-3-ylmethyl)-1H-imidazo[4,5-c]quinoline;

1-[(2R,4R)-2-ethyltetrahydro-2H-pyran-4-yl]-2-(1,2-oxazol-3-ylmethyl)-1H-imidazo[4,5-c]quinoline-8-carbonitrile;

1-[(2R,4R)-2-methyltetrahydro-2H-pyran-4-yl]-2-(1,2-oxazol-3-ylmethyl)-1H-imidazo[4,5-c][1,5]naphthyridine;

2-(imidazo[2,1-b][1,3,4]thiadiazol-6-ylmethyl)-1-(tetrahydro-2H-pyran-4-yl)-1H-imidazo[4,5-c]quinoline;

1-(2,2-dimethyltetrahydro-2H-pyran-4-yl)-8-fluoro-2-[(5-methoxypyridin-2-yl)methyl]-1H-imidazo[4,5-c]quinoline;

2-[(2-chloroimidazo[2,1-b][1,3]thiazol-6-yl)methyl]-1-(tetrahydro-2H-pyran-4-yl)-1H-imidazo[4,5-c]quinoline;

1-(2,2-dimethyltetrahydro-2H-pyran-4-yl)-2-(1,3-thiazol-4-ylmethyl)-1H-imidazo[4,5-c]quinoline;

1-(2,2-dimethyltetrahydro-2H-pyran-4-yl)-2-(imidazo[2,1-b][1,3,4]thiadiazol-6-ylmethyl)-1H-imidazo[4,5-c]quinoline;

8-fluoro-1-(tetrahydro-2H-pyran-4-yl)-2-{[4-(trifluoromethyl)-1H-1,2,3-triazol-1-yl]methyl}-1H-imidazo[4,5-c]quinoline;

8-fluoro-2-(1,2-oxazol-3-ylmethyl)-1-(tetrahydro-2H-pyran-4-yl)-1H-imidazo[4,5-c]quinoline;

8-fluoro-2-(2H-indazol-2-ylmethyl)-1-(tetrahydro-2H-pyran-4-yl)-1H-imidazo[4,5-c]quinoline;

8-fluoro-1-(tetrahydro-2H-pyran-4-yl)-2-(1,3-thiazol-4-ylmethyl)-1H-imidazo[4,5-c]quinoline;

8-fluoro-1-(tetrahydro-2H-pyran-4-yl)-2-{[4-(trifluoromethyl)-1H-pyrazol-1-yl]methyl}-1H-imidazo[4,5-c]quinoline;

2-[(4-cyclopropyl-1H-1,2,3-triazol-1-yl)methyl]-1-(2,2-dimethyltetrahydro-2H-pyran-4-yl)-8-fluoro-1H-imidazo[4,5-c]quinoline;

1-(2,2-dimethyltetrahydro-2H-pyran-4-yl)-8-fluoro-2-(1,3-thiazol-4-ylmethyl)-1H-imidazo[4,5-c]quinoline;

1-(2,2-dimethyltetrahydro-2H-pyran-4-yl)-8-fluoro-2-{[4-(trifluoromethyl)-1H-pyrazol-1-yl]methyl}-1H-imidazo[4,5-c]quinoline;

8-fluoro-2-(imidazo[2,1-b][1,3,4]thiadiazol-6-ylmethyl)-1-(tetrahydro-2H-pyran-4-yl)-1H-imidazo[4,5-c]quinoline;

1-(2,2-dimethyltetrahydro-2H-pyran-4-yl)-8-fluoro-2-[(2-methyl imidazo[2,1-b][1,3,4]thiadiazol-6-yl)methyl]-1H-imidazo[4,5-c]quinoline;

1-(2,2-dimethyltetrahydro-2H-pyran-4-yl)-8-fluoro-2-(1,2-oxazol-3-ylmethyl)-1H-imidazo[4,5-c]quinoline;

8-chloro-1-[(2R,4R)-2-methyltetrahydro-2H-pyran-4-yl]-2-(1,3-thiazol-4-ylmethyl)-1H-imidazo[4,5-c]quinolin-4-amine;

8-fluoro-2-(imidazo[2,1-b][1,3,4]thiadiazol-6-ylmethyl)-1-(cis-2-methyltetrahydro-2H-pyran-4-yl)-1H-imidazo[4,5-c]quinoline;

8-methoxy-2-[(5-methyl-1,2,4-oxadiazol-3-yl)methyl]-1-[(2R,4R)-2-methyltetrahydro-2H-pyran-4-yl]-1H-imidazo[4,5-c]quinoline;

8-methoxy-1-[(2R,4R)-2-methyltetrahydro-2H-pyran-4-yl]-2-[(4-methyl-1H-1,2,3-triazol-1-yl)methyl]-1H-imidazo[4,5-c]quinoline;

8-methoxy-1-[(2R,4R)-2-methyltetrahydro-2H-pyran-4-yl]-2-(1,3-thiazol-4-ylmethyl)-1H-imidazo[4,5-c]quinoline;

2-(imidazo[2,1-b][1,3,4]thiadiazol-6-ylmethyl)-8-methoxy-1-[(2R,4R)-2-methyltetrahydro-2H-pyran-4-yl]-1H-imidazo[4,5-c]quinoline;

[cis-4-(2-methyl-1H-imidazo[4,5-c]quinolin-1-yl)tetrahydro-2H-pyran-2-yl]acetonitrile; and

8-chloro-2-[(5-methyl-1,3-oxazol-2-yl)methyl]-1-[(2R,4R)-2-methyltetrahydro-2H-pyran-4-yl]-1H-imidazo[4,5-c]quinoline;

or a pharmaceutically acceptable salt thereof.

17. A compound of claim 2 selected from the group consisting of

8-chloro-2-[(5-methoxypyridin-2-yl)methyl]-1-[(2R,4R)-2-methyltetrahydro-2H-pyran-4-yl]-1H-imidazo[4,5-c]quinoline;

2-[(5-methyl-1,2-oxazol-3-yl)methyl]-1-[(2R,4R)-2-methyltetrahydro-2H-pyran-4-yl]-1H-imidazo[4,5-c]quinoline-8-carbonitrile;

8-chloro-2-[(5-methyl-1,2-oxazol-3-yl)methyl]-1-[(2R,4R)-2-methyltetrahydro-2H-pyran-4-yl]-1H-imidazo[4,5-c]quinoline;

8-chloro-2-[(5-methyl-1,2,4-oxadiazol-3-yl)methyl]-1-[(2R,4R)-2-methyltetrahydro-2H-pyran-4-yl]-1H-imidazo[4,5-c]quinoline;

8-chloro-2-(imidazo[2,1-b][1,3,4]thiadiazol-6-ylmethyl)-1-[(2R,4R)-2-methyltetrahydro-2H-pyran-4-yl]-1H-imidazo[4,5-c]quinoline;

{8-chloro-1-[(2R,4R)-2-methyltetrahydro-2H-pyran-4-yl]-1H-imidazo[4,5-c]quinolin-2-yl}acetonitrile;

8-chloro-1-[(2R,4R)-2-methyltetrahydro-2H-pyran-4-yl]-2-(1,3-thiazol-4-ylmethyl)(4- 2 H)-1H-imidazo[4,5-c]quinoline; and

8-chloro-1-[(2R,4R)-2-methyltetrahydro-2H-pyran-4-yl]-2-[(4-methyl-1H-1,2,3-triazol-1-yl)methyl]-1H-imidazo[4,5-c]quinoline;

or a pharmaceutically acceptable salt thereof.

18. The compound of claim 2 or a pharmaceutically acceptable salt thereof wherein

X is CR 7 ;

Z is CR 3 ;

R 1a , R 1b , R 4 , R 5 , R 6 and R 7 are each hydrogen; and

R 3 is chloro or cyano.

19. The compound of claim 18 or a pharmaceutically acceptable salt thereof wherein

R 2 is 1-methylpyrrolidinyl or 2-methyltetrahydropyranyl.

20. The compound of claim 19 or a pharmaceutically acceptable salt thereof wherein

R 1 is selected from the group consisting of isoxazolyl, pyrazolyl, triazolyl, oxadiazolyl, thiadiazolyl, pyrimidinyl and pyrazinyl; each of which is optionally substituted with an R 8 ; and R 8 is methyl or methoxy.

21. The compound of claim 20 or a pharmaceutically acceptable salt thereof wherein

R 1 is selected from the group consisting of methylisoxazolyl, methoxypyrazolyl, methyltriazolyl, methyloxadiazolyl, methylthiadiazolyl, methylpyrimidinyl and methylpyrazinyl;

R 2 is (2R, 4R)-2-methyltetrahydro-2H-pyran-4-yl; and

R 3 is chloro.

22. The compound of claim 20 or a pharmaceutically acceptable salt thereof wherein

R 1 is selected from the group consisting of methylisoxazolyl, methoxypyrazolyl, methyltriazolyl, methyloxadiazolyl, methylthiadiazolyl, methylpyrimidinyl and methylpyrazinyl;

R 2 is 1-methylpyrrolidinyl; and

R 3 is cyano.

23. The compound of claim 20 selected from the group consisting of

8-Chloro-2-[(5-methyl-1,2-oxazol-3-yl)methyl]-1-[(2R,4R)-2-methyltetrahydro-2H-pyran-4-yl]-1H-imidazo[4,5-c]quinoline;

8-Chloro-2-[(5-methyl-1,2,4-oxadiazol-3-yl)methyl]-1-[(2R,4R)-2-methyltetrahydro-2H-pyran-4-yl]-1H-imidazo[4,5-c]quinoline;

8-Chloro-1-[(2R,4R)-2-methyltetrahydro-2H-pyran-4-yl]-2-[(4-methyl-1H-1,2,3-triazol-1-yl)methyl]-1H-imidazo[4,5-c]quinoline;

8-Chloro-2-[(6-methylpyrimidin-4-yl)methyl]-1-[(2R,4R)-2-methyltetrahydro-2H-pyran-4-yl]-1H-imidazo[4,5-c]quinoline;

8-Chloro-2-[(5-methylpyrazin-2-yl)methyl]-1-[(2R,4R)-2-methyltetrahydro-2H-pyran-4-yl]-1H-imidazo[4,5-c]quinoline;

8-Chloro-2-[(4-methoxy-1H-pyrazol-1-yl)methyl]-1-[(2R,4R)-2-methyltetrahydro-2H-pyran-4-yl]-1H-imidazo[4,5-c]quinoline; and

8-Chloro-1-[(2R,4R)-2-methyltetrahydro-2H-pyran-4-yl]-2-[(5-methyl-1,3,4-thiadiazol-2-yl)methyl]-1H-imidazo[4,5-c]quinoline;

or a pharmaceutically acceptable salt thereof.

24. A pharmaceutical composition comprising a therapeutically effective amount of a compound according to claim 1 , or a pharmaceutically acceptable salt thereof together with a pharmaceutically acceptable carrier.

25. The corn pound 8-Chloro-2-[(6-methylpyrimidin-4-yl)methyl]-1-[(2R,4R)-2-methyltetrahydro-2H-pyran-4-yl]-1H-imidazo[4,5-c]quinoline; or a pharmaceutically acceptable salt thereof.

26. The corn pound 8-Chloro-2-[(5-methylpyrazin-2-yl)methyl]-1-[(2R,4R)-2-methyltetrahydro-2H-pyran-4-yl]-1H-imidazo[4,5-c]quinoline; or a pharmaceutically acceptable salt thereof.

27. The corn pound 8-Chloro-2-[(4-methoxy-1H-pyrazol-1-yl)methyl]-1-[(2R,4R)-2-methyltetrahydro-2H-pyran-4-yl]-1H-imidazo[4,5-c]quinoline; or a pharmaceutically acceptable salt thereof.

28. The corn pound 8-Chloro-1-[(2R,4R)-2-methyltetrahydro-2H-pyran-4-yl]-2-[(5-methyl-1,3,4-thiadiazol-2yl)methyl]-1H-imidazo[4,5-c]quinoline; or a pharmaceutically acceptable salt thereof.

29. The compound 8-Chloro-2-[(5-methyl-1,2,4-oxadiazol-3-yl)methyl]-1-[(2R,4R)-2-methyltetrahydro-2H-pyran-4-yl]-1H-imidazo[4,5-c]quinoline; or a pharmaceutically acceptable salt thereof.