Fused bicylic pyridine compounds and their use as AMPA receptor modulators

Patent metadata

Field	Value
Publication number	US-10087185-B2
Application number	US-201715790849-A
Country	US
Kind code	B2
Filing date	Oct 23, 2017
Priority date	Oct 26, 2016
Publication date	Oct 2, 2018
Grant date	Oct 2, 2018

Abstract

Provided herein are compounds of Formula (I), and pharmaceutically acceptable salts, N-oxides, or solvates thereof,

Also provided herein are pharmaceutical compositions comprising compounds of Formula (I) and methods of using compounds of Formula (I).

First claim

What is claimed:

1. A compound of Formula (I):

wherein
Y is N or CH;
R 1 is selected from the group consisting of: H, halo, and C 1-6 alkyl;
R 2 is selected from the group consisting of: C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, and C 3-8 cycloalkyl;
R 3 is selected from the group consisting of: H, halo, C 1-6 alkyl, C 1-6 alkoxy, CN, and CF 3 ;
R 4 is selected from the group consisting of: C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, phenyl substituted with F, and pyridyl; and

is selected from the group consisting of: —CH═N—, —CH 2 —C(═O)—, and —S—C(═O)—; and
pharmaceutically acceptable salts, N-oxides, or solvates thereof.

2. The compound of claim 1 , wherein Y is N.

3. The compound of claim 1 , wherein Y is CH.

4. The compound of claim 1 , wherein R 1 is H.

5. The compound of claim 1 , wherein R 1 is Cl or F.

6. The compound of claim 1 , wherein R 1 is CH 3 or CH 2 CH 3 .

7. The compound of claim 1 , wherein R 2 is CF 3 , CHF 2 , or CF 2 (CH 3 ).

8. The compound of claim 1 , wherein R 2 is CH 3 , CH 2 CH 3 , CH 2 CH 2 CH 3 , or CH(CH 3 ) 2 .

9. The compound of claim 1 , wherein R 2 is cyclopropyl.

10. The compound of claim 1 , wherein R 2 is OCH 3 or OCH 2 CH 3 .

11. The compound of claim 1 , wherein R 3 is H, Cl, CH 3 , or CH 2 CH 3 .

12. The compound of claim 1 , wherein R 3 is OCH 3 or CN.

13. The compound of claim 1 , wherein R 3 is CF 3 .

14. The compound of claim 1 , wherein R 4 is CF 3 , CF 2 (CH 3 ), or CHF 2 .

15. The compound of claim 1 , wherein R 4 is OCH 3 .

16. The compound of claim 1 , wherein R 4 is CH 2 CH 3 .

17. The compound of claim 1 , wherein R 4 is 4-fluorophenyl, pyridin-3-yl, or pyridin-4-yl.

18. The compound of claim 1 , wherein

is —CH═N—.

19. The compound of claim 1 , wherein

is —CH 2 —C(═O)—.

20. The compound of claim 1 , wherein

is —S—C(═O)—.

21. The compound of claim 1 , and pharmaceutically acceptable salts, solvates, or N-oxides thereof, having the structure of Formula (1A):

wherein
R 1 is selected from the group consisting of: H, halo, CH 3 , and CH 2 CH 3 ;
R 2 is selected from the group consisting of: C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, and C 3-8 cycloalkyl;
R 4 is selected from the group consisting of: C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, phenyl substituted with F, and pyridyl; and
R 5 is selected from the group consisting of:

22. The compound of claim 1 , and pharmaceutically acceptable salts, solvates, or N-oxides thereof, having the structure of Formula (1B):

wherein
R 1 is H, or C 1-6 alkyl;
R 2 is selected from the group consisting of: C 1-6 alkyl, C 1-6 haloalkyl, and C 3-8 cycloalkyl;
R 4 is CF 2 H or CF 3 ; and
R 5 is selected from the group consisting of:

23. A compound selected from the group consisting of:
5-(7-Chloro-1H-indazol-5-yl)-2,6-bis(trifluoromethyl)-[1,2,4]triazolo[1,5-a]pyridine;
5-(7-Methyl-1H-indazol-5-yl)-2,6-bis(trifluoromethyl)-[1,2,4]triazolo[1,5-a]pyridine;
5-(2,6-Bis(trifluoromethyl)-[1,2,4]triazolo[1,5-a]pyridin-5-yl)-7-chloroindolin-2-one;
5-(2,6-Bis(trifluoromethyl)-[1,2,4]triazolo[1,5-a]pyridin-5-yl)-7-methylindolin-2-one;
8-Chloro-5-(7-chloro-1H-indazol-5-yl)-2,6-bis(trifluoromethyl)-[1,2,4]triazolo[1,5-a]pyridine;
5-(7-Chloro-1H-indazol-5-yl)-8-methyl-2,6-bis(trifluoromethyl)-[1,2,4]triazolo[1,5-a]pyridine;
5-(7-Chloro-1H-indazol-5-yl)-2-(difluoromethyl)-6-(trifluoromethyl)-[1,2,4]triazolo[1,5-a]pyridine;
5-(7-Methyl-1H-indazol-5-yl)-2-(difluoromethyl)-6-(trifluoromethyl)-[1,2,4]triazolo[1,5-a]pyridine;
7-Chloro-5-(2-(difluoromethyl)-6-(trifluoromethyl)-[1,2,4]triazolo[1,5-a]pyridin-5-yl)indolin-2-one;
7-Methyl-5-(2-(difluoromethyl)-6-(trifluoromethyl)-[1,2,4]triazolo[1,5-a]pyridin-5-yl)indolin-2-one;
2-(Difluoromethyl)-6-(trifluoromethyl)-5-(7-(trifluoromethyl)-1H-indazol-5-yl)-[1,2,4]triazolo[1,5-a]pyridine;
5-(2-(Difluoromethyl)-6-(trifluoromethyl)-[1,2,4]triazolo[1,5-a]pyridin-5-yl)-7-methoxyindolin-2-one;
5-(7-Chloro-1H-indazol-5-yl)-2-(difluoromethyl)-6-methoxy-[1,2,4]triazolo[1,5-a]pyridine;
2-(Difluoromethyl)-6-methoxy-5-(7-methyl-1H-indazol-5-yl)-[1,2,4]triazolo[1,5-a]pyridine;
2-(Difluoromethyl)-6-methoxy-5-(7-(trifluoromethyl)-1H-indazol-5-yl)-[1,2,4]triazolo[1,5-a]pyridine;
5-(7-Chloro-1H-indazol-5-yl)-6-(difluoromethyl)-2-(trifluoromethyl)-[1,2,4]triazolo[1,5-a]pyridine;
6-(Difluoromethyl)-5-(7-methyl-1H-indazol-5-yl)-2-(trifluoromethyl)-[1,2,4]triazolo[1,5-a]pyridine;
7-Chloro-5-(6-(difluoromethyl)-2-(trifluoromethyl)-[1,2,4]triazolo[1,5-a]pyridin-5-yl)indolin-2-one;
5-[6-(Difluoromethyl)-2-(trifluoromethyl)-[1,2,4]triazolo[1,5-a]pyridin-5-yl]-7-methyl-indolin-2-one;
5-[6-(Difluoromethyl)-2-(trifluoromethyl)-[1,2,4]triazolo[1,5-a]pyridin-5-yl]-7-methoxy-indolin-2-one;
5-(7-Chloro-1H-indazol-5-yl)-2-methyl-6-(trifluoromethyl)-[1,2,4]triazolo[1,5-a]pyridine;
2-Methyl-5-(7-methyl-1H-indazol-5-yl)-6-(trifluoromethyl)-[1,2,4]triazolo[1,5-a]pyridine;
7-Chloro-5-(2-methyl-6-(trifluoromethyl)-[1,2,4]triazolo[1,5-a]pyridin-5-yl)indolin-2-one;
7-Methyl-5-(2-methyl-6-(trifluoromethyl)-[1,2,4]triazolo[1,5-a]pyridin-5-yl)indolin-2-one;
5-(7-Chloro-1H-indazol-5-yl)-2-ethyl-6-(trifluoromethyl)-[1,2,4]triazolo[1,5-a]pyridine;
2-Ethyl-5-(7-methyl-1H-indazol-5-yl)-6-(trifluoromethyl)-[1,2,4]triazolo[1,5-a]pyridine;
7-Chloro-5-(2-ethyl-6-(trifluoromethyl)-[1,2,4]triazolo[1,5-a]pyridin-5-yl)indolin-2-one;
5-(2-Ethyl-6-(trifluoromethyl)-[1,2,4]triazolo[1,5-a]pyridin-5-yl)-7-methylindolin-2-one;
8-Chloro-5-(7-chloro-1H-indazol-5-yl)-2-ethyl-6-(trifluoromethyl)-[1,2,4]triazolo[1,5-a]pyridine;
8-Chloro-2-ethyl-5-(7-methyl-1H-indazol-5-yl)-6-(trifluoromethyl)-[1,2,4]triazolo[1,5-a]pyridine;
5-(7-Chloro-1H-indazol-5-yl)-2-ethyl-8-fluoro-6-(trifluoromethyl)-[1,2,4]triazolo[1,5-a]pyridine;
7-Chloro-5-[2-ethyl-8-fluoro-6-(trifluoromethyl)-[1,2,4]triazolo[1,5-a]pyridin-5-yl]indolin-2-one;
2-Cyclopropyl-8-fluoro-5-(7-methyl-1H-indazol-5-yl)-6-(trifluoromethyl)-[1,2,4]triazolo[1,5-a]pyridine;
5-(7-Chloro-1H-indazol-5-yl)-8-fluoro-2-isopropyl-6-(trifluoromethyl)-[1,2,4]triazolo[1,5-a]pyridine;
5-(7-Chloro-1H-indazol-5-yl)-2-ethyl-8-methyl-6-(trifluoromethyl)-[1,2,4]triazolo[1,5-]pyridine;
5-(7-Chloro-1H-indazol-5-yl)-2-isopropyl-6-(trifluoromethyl)-[1,2,4]triazolo[1,5-a]pyridine;
2-Isopropyl-5-(7-methyl-1H-indazol-5-yl)-6-(trifluoromethyl)-[1,2,4]triazolo[1,5-a]pyridine;
5-(7-Chloro-1H-indazol-5-yl)-2-cyclopropyl-6-(trifluoromethyl)-[1,2,4]triazolo[1,5-a]pyridine;
2-Cyclopropyl-5-(7-methyl-1H-in

Assignees

• Janssen Pharmaceutica Nv

Inventors

• Ameriks Michael K
• GYURIS Márió
• Laforteza Brian Ngo
• Lebold Terry Patrick
• Meyer Stephen Todd
• Ravula Suchitra
• Savall Brad M
• Shireman Brock T
• Wade Warren Stanfield
• Gerencsér János

Classifications

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P9/10

  for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis · CPC title

• A61P25/06

  Antimigraine agents · CPC title

• A61P25/14

  for treating abnormal movements, e.g. chorea, dyskinesia · CPC title

• A61P25/02

  for peripheral neuropathies · CPC title