Imidazo[4,5-C]pyridine and pyrrolo[2,3-C]pyridine derivatives as SSAO inhibitors

1. A compound of formula (I) or a pharmaceutically acceptable salt, or N-oxide thereof:

Wherein:

Y is selected from hydrogen, hydroxyl, —NH 2 , —NH—C 1-4 -alkyl, —NH-halo-C 1-4 -alkyl, or —C 1-4 -alkoxy;

Z is selected from hydrogen, halogen, hydroxyl, cyano, C 1-4 -alkyl, halo-C 1-4 -alkyl, C 1-4 -alkoxy, halo-C 1-4 -alkoxy, —CONH 2 , —SO 2 NH 2 , —NH 2 , —NHC 1-4 -alkyl, or —NHhalo-C 1-4 -alkyl;

R 1 is a phenyl ring, or a 5 or 6-membered heteroaryl ring, either ring being optionally substituted with one or more substituents selected from halogen, cyano, C 1-4 -alkyl, halo-C 1-4 -alkyl, cyano-C 1-4 -alkyl, a 3-7 membered cycloalkyl ring, —OR 5 , —NR 6 C(O)OR 5 , —NR 6 C(O)R 5 , —NR 6 C(O)NR 4A R 4B , —C(O)NR 4A R 4B , —C(O)R 5 , —C(O)OR 5 , and —NR 6 S(O) 2 R 5 ; wherein

R 4A , R 4B R 5 and R 6 are each independently selected from hydrogen, C 1-4 -alkyl or halo-C 1-4 -alkyl, or

R 4A and R 4B together with the nitrogen to which they are attached form a 3-7 membered cyclic amino group, optionally substituted by one or more substituents selected from: halogen, hydroxyl, cyano, C 1-4 -alkyl, halo-C 1-4 -alkyl, C 1-4 -alkoxy, halo-C 1-4 -alkoxy, —CONH 2 , —SO 2 NH 2 , —NH 2 , —NHC 1-4 -alkyl, —NHhalo-C 1-4 -alkyl;

X is —C(R 2 )═;

R 2 is selected from hydrogen, halogen, cyano, C 1-4 -alkyl, halo-C 1-4 -alkyl, cyano-C 1-4 -alkyl, —OR 5 , —NR 4A R 4B , —NR 6 C(O)OR 5 , —NR 6 C(O)R 5 , —NR 6 C(O)NR 4A R 4B , —SO 2 R 5 , —SO 2 NR 4A R 4B and —NR 6 S(O) 2 R 5 ;

W is a phenyl ring or a 5 or 6-membered heteroaryl ring, either ring being optionally substituted with one or more substituents selected from halogen, cyano, oxo C 1-4 -alkyl, halo-C 1-4 -alkyl, cyano-C 1-4 -alkyl, —OR 5 , —NR 7A R 7B , —NR 6 C(O)OR 5 , —NR 6 C(O)R 5 , —NR 6 C(O)NR 7A R 7B , —C(O)NR 7A R 7B , —C(O)R 5 , —C(O)OR 5 , —SO 2 R 5 , —SO 2 NR 7A R 7B and —NR 6 S(O) 2 R 5 ;

R 7A and R 7B are independently hydrogen, C 1-4 -alkyl or halo-C 1-4 -alkyl;

V is selected from a bond, —O—, —N(R 6 )—, —(C═O)—, —CONR 6 —, —NR 6 C(O)—, or —C 1-4 -alkylene-, wherein the C 1-4 -alkylene group is optionally substituted by halogen, and wherein any one of the carbon atoms of the C 1-4 -alkylene group may be replaced by —O— or —N(R 6 )—;

R 3 is selected from hydrogen, —C 1-4 -alkyl, —C 1-4 -alkyl-C 1-4 -alkoxy or a 3-7 membered heterocyclic ring or 3-7 membered cycloalkyl ring, or a 5 or 6-membered heteroaryl ring, any one of the rings being optionally substituted with one or more substituents selected from halogen, oxo, hydroxyl, cyano, C 1-4 -alkyl, halo-C 1-4 -alkyl, cyano-C 1-4 -alkyl, —OR 5 , —NR 4A R 4B , —NR 6 C(O)OR 5 , —NR 6 C(O)R 5 , —NR 6 C(O)NR 4A R 4B , —C(O)NR 4A R 4B , —C(O)R 5 , —C(O)OR 5 , —SO 2 R 5 , —SO 2 NR 4A R 4B and —NR 6 S(O) 2 R 5

PROVIDED THAT groups —WVR 3 and/or R 1 are not:

wherein

n is 0, 1, or 2;

R′ and R″ are independently selected from the group consisting of H, —C 1 -C 6 alkyl, —(C═O)—C 1 -C 6 alkyl and —(C═O)OC(CH 3 ) 3 ; and

R′″ is H, OH, or C 1 -C 6 alkyl; and

FURTHER PROVIDED THAT when —R 3 is H, R 1 is not a phenyl ring substituted with one —OCH 3 .

2. A compound of formula (I) or a pharmaceutically acceptable salt, or N-oxide thereof:

Wherein:

Y is selected from hydrogen, hydroxyl, —NH 2 , —NH—C 1-4 -alkyl, —NH-halo-C 1-4 -alkyl, or —C 1-4 -alkoxy;

Z is selected from hydrogen, halogen, hydroxyl, cyano, C 1-4 -alkyl, halo-C 1-4 -alkyl, C 1-4 -alkoxy, halo-C 1-4 -alkoxy, —CONH 2 , —SO 2 NH 2 , —NH 2 , —NHC 1-4 -alkyl, or —NHhalo-C 1-4 -alkyl;

R 1 is a phenyl ring, or a 5 or 6-membered heteroaryl ring, either ring being optionally substituted with one or more substituents selected from halogen, cyano, C 1-4 -alkyl, halo-C 1-4 -alkyl, cyano-C 1-4 -alkyl, —OR 5 , —NR 6 C(O)OR 5 , —NR 6 C(O)R 5 , —NR 6 C(O)NR 4A R 4B , —C(O)NR 4A R 4B , —C(O)R 5 , —C(O)OR 5 , and —NR 6 S(O) 2 R 5 ; wherein

R 4A , R 4B R 5 and R 6 are each independently selected from hydrogen, C 1-4 -alkyl or halo-C 1-4 -alkyl, or

R 4A and R 4B together with the nitrogen to which they are attached form a 3-7 membered cyclic amino group, optionally substituted by one or more substituents selected from: halogen, hydroxyl, cyano, C 1-4 -alkyl, halo-C 1-4 -alkyl, C 1-4 -alkoxy, halo-C 1-4 -alkoxy, —CONH 2 , —SO 2 NH 2 , —NH 2 , —NHC 1-4 -alkyl, —NHhalo-C 1-4 -alkyl;

X is —C(R 2 )═;

R 2 is selected from hydrogen, halogen, cyano, C 1-4 -alkyl, halo-C 1-4 -alkyl, cyano-C 1-4 -alkyl, —OR 5 , —NR 4A R 4B , —NR 6 C(O)OR 5 , —NR 6 C(O)R 5 , —NR 6 C(O)NR 4A R 4B , C(O)NR 4A R 4B , —C(O)R 5 , —C(O)OR 5 , —SO 2 R 5 , —SO 2 NR 4A R 4B and —NR 6 S(O) 2 R 5 ;

W is a phenyl ring or a 5 or 6-membered heteroaryl ring, either ring being optionally substituted with one or more substituents selected from halogen, cyano, C 1-4 -alkyl, halo-C 1-4 -alkyl, cyano-C 1-4 -alkyl, —OR 5 , —NR 7A R 7B , —NR 6 C(O)OR 5 , —NR 6 C(O)R 5 , —NR 6 C(O)NR 7A R 7B , —SO 2 R 5 , —SO 2 NR 7A R 7B and —NR 6 S(O) 2 R 5 ;

R 7A and R 7B are independently hydrogen, C 1-4 -alkyl or halo-C 1-4 -alkyl;

V is selected from a bond, —O—, —N(R 6 )—, —(C═O)—, —CONR 6 —, —NR 6 C(O)—, or —C 1-4 -alkylene-, wherein the C 1-4 -alkylene group is optionally substituted by halogen, and wherein any one of the carbon atoms of the C 1-4 -alkylene group may be replaced by —O— or —N(R 6 )—;

R 3 is hydrogen, or a 3-7 membered heterocyclic ring, or 3-7 membered cycloalkyl ring selected from cyclopropyl, cyclopentyl or cyclohexyl, or a 5 or 6-membered heteroaryl ring, any one of the rings being optionally substituted with one or more substituents selected from halogen, oxo, hydroxyl, cyano, C 1-4 -alkyl, halo-C 1-4 -alkyl, cyano-C 1-4 -alkyl, —OR 5 , —NR 4A R 4B , —NR 6 C(O)OR 5 , —NR 6 C(O)R 5 , —NR 6 C(O)NR 4A R 4B , —C(O)NR 4A R 4B , —C(O)R 5 , —C(O)OR 5 , —SO 2 R 5 , —SO 2 NR 4A R 4B and —NR 6 S(O) 2 R 5 ;

PROVIDED THAT when —R 3 is H, R 1 is not a phenyl ring substituted with one —OCH 3 .

3. A compound according to claim 1 , wherein Y is hydrogen.

4. A compound according to claim 1 , wherein Z is hydrogen.

5. A compound according to claim 1 , wherein R 1 is phenyl or 6-membered heteroaryl, optionally substituted with one or more substituents selected from halogen, C 1-4 -alkyl or halo-C 1-4 -alkyl.

6. A compound according to claim 1 , wherein R 1 is phenyl or pyridyl, optionally substituted with one or more substituents selected from F, Cl or CH 3 .

7. A compound according to claim 1 , wherein R 2 is hydrogen, halogen, cyano, C 1-4 -alkyl, or halo-C 1-4 -alkyl.

8. A compound according to claim 1 , wherein R 2 is hydrogen.

9. A compound according to claim 1 , wherein W is a phenyl ring optionally substituted with one or more substituents as defined in claim 1 .

10. A compound according to claim 1 , wherein W is a 6-membered heteroaryl ring selected from pyridine, pyridazine, pyrazine, or pyrimidine optionally substituted with one or more substituents as defined in claim 1 .

11. A compound according to claim 1 , wherein W is a 5-membered heteroaryl ring selected from oxazole, thiazole or imidazole optionally substituted with one or more substituents as defined in claim 1 .

12. A compound according to claim 1 , wherein W is an imidazolyl ring optionally substituted as in claim 1 , and wherein the imidazolyl ring is connected to the pyrrolopyridine core via an imidazolyl ring carbon atom.

13. A compound according to claim 1 , wherein W is optionally substituted with one or more substituents selected from fluoro, chloro, cyano, CH 3 or CF 3 .

14. A compound according to claim 1 , wherein V is —CH 2 —, —(CH 2 ) 2 —, or —N(R 6 )CH 2 —, or —CH 2 —N(R 6 )—.

15. A compound according to claim 1 , wherein R 3 is cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl optionally substituted as defined in claim 1 .

16. A compound according to claim 1 , wherein R 3 is formed from —NR 4A R 4B wherein R 4A and R 4B , together with the nitrogen atom to which they are attached join together to form a 4-7 membered heterocyclic ring optionally substituted as defined in claim 1 .

17. A compound according to claim 1 , wherein R 3 is selected from the group consisting of:

wherein R 8 is selected from hydrogen, CH 3 , —CONH 2 , —NHCONH 2 , —S(O) 2 CH 3 , —COCH 3 .

18. A compound according to claim 1 , wherein R 1 is a phenyl ring, or a 5 or 6-membered heteroaryl ring, either ring being optionally substituted with one or more 3-7 membered cycloalkyl rings.

19. A compound according to claim 1 , wherein W is a phenyl ring or a 5 or 6-membered heteroaryl ring, either ring being optionally substituted with one or more oxo substituents.

20. A compound according to claim 1 , wherein R 3 is selected from —C 1-4 -alkyl or —C 1-4 -alkyl-C 1-4 -alkoxy.

21. A compound according to claim 1 selected from:

4-[1-(4-Chlorophenyl)-1H-pyrrolo[2,3-c]pyridin-2-yl]pyridine (Example 120);

2-[1-(4-Chlorophenyl)-1H-pyrrolo[2,3-c]pyridin-2-yl]pyridine (Example 121);

3-[1-(4-Chlorophenyl)-1H-pyrrolo[2,3-c]pyridin-2-yl]pyridine (Example 122);

5-[1-(4-Chlorophenyl)-1H-pyrrolo[2,3-c]pyridin-2-yl]pyrimidine (Example 123);

2-[1-(4-Chlorophenyl)-1H-pyrrolo[2,3-c]pyridin-2-yl]pyrazine (Example 124);

1-({4-[1-(4-Chlorophenyl)-1H-pyrrolo[2,3-c]pyridin-2-yl]phenyl}carbonyl)-4-methylpiperazine (Example 125);

4-{5-[1-(4-Chlorophenyl)-1H-pyrrolo[2,3-c]pyridin-2-yl]pyrimidin-2-yl}morpholine (Example 127);

4-{5-[1-(4-Chlorophenyl)-1H-pyrrolo[2,3-c]pyridin-2-yl]pyrimidin-2-yl}piperazin-2-one (Example 128);

4-{5-[1-(4-Chlorophenyl)-1H-pyrrolo[2,3-c]pyridin-2-yl]-4-methylpyridin-2-yl}morpholine (Example 129);

4-{5-[1-(4-Methylphenyl)-1H-pyrrolo[2,3-c]pyridin-2-yl]pyrimidin-2-yl}morpholine (Example 130);

4-(5-{1-Phenyl-1H-pyrrolo[2,3-c]pyridin-2-yl}pyrimidin-2-yl)morpholine (Example 131);

4-{5-[1-(4-Bromophenyl)-1H-pyrrolo[2,3-c]pyridin-2-yl]pyrimidin-2-yl}morpholine (Example 133);

5-[1-(4-Chlorophenyl)-1H-pyrrolo[2,3-c]pyridin-2-yl]-1-methyl-1H-pyrazole (Example 134);

4-[1-(4-Chlorophenyl)-1H-pyrrolo[2,3-c]pyridin-2-yl]-1-methyl-1H-pyrazole (Example 135);

5-[1-(4-Chlorophenyl)-1H-pyrrolo[2,3-c]pyridin-2-yl]-1-methyl-1H-imidazole (Example 136);

5-[1-(4-Chlorophenyl)-1H-pyrrolo[2,3-c]pyridin-2-yl]-N,N-dimethylpyrimidin-2-amine (Example 137);

4-[1-(4-Chlorophenyl)-1H-pyrrolo[2,3-c]pyridin-2-yl]-1-cyclopropyl-1,2-dihydropyridin-2-one (Example 138);

5-[1-(4-Chlorophenyl)-1H-pyrrolo[2,3-c]pyridin-2-yl]-N-(oxan-4-yl)pyrimidin-2-amine (Example 139);

4-({5-[1-(4-Chlorophenyl)-1H-pyrrolo[2,3-c]pyridin-2-yl]pyridin-2-yl}methyl)morpholine (Example 140);

5-[1-(4-Chlorophenyl)-1H-pyrrolo[2,3-c]pyridin-2-yl]-4-methylpyridin-2-amine (Example 141);

4-[1-(4-Chlorophenyl)-1H-pyrrolo[2,3-c]pyridin-2-yl]-1,2-dihydropyridin-2-one (Example 142);

4-[1-(4-Chlorophenyl)-1H-pyrrolo[2,3-c]pyridin-2-yl]-1-methyl-1,2-dihydropyridin-2-one (Example 143);

4-[1-(4-Chlorophenyl)-1H-pyrrolo[2,3-c]pyridin-2-yl]-1-ethyl-1,2-dihydropyridin-2-one (Example 144);

6-[1-(4-Chlorophenyl)-1H-pyrrolo[2,3-c]pyridin-2-yl]-1-methyl-1,2-dihydropyridin-2-one (Example 145);

5-[1-(4-Chlorophenyl)-1H-pyrrolo[2,3-c]pyridin-2-yl]-2,3-dihydropyridazin-3-one (Example 146);

4-[1-(4-Chlorophenyl)-1H-pyrrolo[2,3-c]pyridin-2-yl]pyridin-2-amine (Example 147);

3-[1-(4-Chlorophenyl)-1H-pyrrolo[2,3-c]pyridin-2-yl]-5-fluoropyridine (Example 148);

5-[1-(4-Chlorophenyl)-1H-pyrrolo[2,3-c]pyridin-2-yl]-N-(cyclopropylmethyl)pyrimidin-2-amine (Example 149);

3-Chloro-5-[1-(4-chlorophenyl)-1H-pyrrolo[2,3-c]pyridin-2-yl]pyridine (Example 150);

5-[1-(4-Chlorophenyl)-1H-pyrrolo[2,3-c]pyridin-2-yl]-2-(1H-pyrazol-1-yl)pyridine (Example 151);

4-[1-(4-Chlorophenyl)-1H-pyrrolo[2,3-c]pyridin-2-yl]-3-fluoropyridine (Example 152);

3-Chloro-4-[1-(4-chlorophenyl)-1H-pyrrolo[2,3-c]pyridin-2-yl]pyridine (Example 153);

4-[1-(4-Chlorophenyl)-1H-pyrrolo[2,3-c]pyridin-2-yl]-3-methylpyridine (Example 154);

1-Cyclopropyl-4-{1-phenyl-1H-pyrrolo[2,3-c]pyridin-2-yl}-1,2-dihydropyridin-2-one (Example 155);

and pharmaceutically acceptable salts thereof.