Fused azaheterocyclic compounds and their use as AMPA receptor modulators

Patent metadata

Field	Value
Publication number	US-10155769-B2
Application number	US-201715790809-A
Country	US
Kind code	B2
Filing date	Oct 23, 2017
Priority date	Oct 26, 2016
Publication date	Dec 18, 2018
Grant date	Dec 18, 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
X is N or CH;
Y is selected from the group consisting of: N, CH, CF, and CCl;
R 1 is H or CH 3 ;
R 2 is selected from the group consisting of: C 1-6 alkyl, C 1-6 haloalkyl, CH 2 OCH 3 , C 3-8 cycloalkyl and phenyl;
R 3 is selected from the group consisting of: H, halo, CH 3 , and CF 3 ;
R 4 is selected from the group consisting of: halo, C 1-6 alkyl, C 1-6 alkoxy, C 1-6 haloalkyl, CN, C 3-8 cycloalkyl, azetidinyl, azetidinyl substituted with F, and phenyl substituted with F; and

 is selected from the group consisting of: —CH═N—; —CF═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 X is N.

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

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

5. The compound of claim 1 , wherein Y is CH, CF, or CCl.

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

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

8. The compound of claim 1 , wherein R 1 is CH 3 .

9. The compound of claim 1 , wherein R 2 is C 1-6 alkyl, C 1-6 haloalkyl, CH 2 OCH 3 , cyclopropyl, cyclobutyl, cyclopentyl, or phenyl.

10. The compound of claim 1 , wherein R 2 is CH 3 , CH 2 CH 3 , CH(CH 3 ) 2 , C(CH 3 ) 3 , CF 2 H, CF 3 .

11. The compound of claim 1 , wherein R 2 is CF 3 .

12. The compound of claim 1 , wherein R 3 is H, F, Cl, or CH 3 .

13. The compound of claim 1 , wherein R 4 is C 1-6 alkyl, C 1-6 haloalkyl, Cl, CN, OCH 3 , phenyl substituted with F, cyclopropyl, cyclopentyl, azetidinyl, or azetidinyl substituted with F.

14. The compound of claim 1 , wherein R 4 is CF 3 .

15. The compound of claim 1 , wherein

is —CH═N—.

16. The compound of claim 1 , wherein

is CH 2 —C(═O)—.

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

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

18. 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;
R 2 is selected from the group consisting of: C 1-6 alkyl, C 1-6 haloalkyl, CH 2 OCH 3 , C 3-8 cycloalkyl and phenyl;
R 4 is selected from the group consisting of: halo, C 1-6 alkyl, C 1-6 alkoxy, C 1-6 haloalkyl, CN, C 3-8 cycloalkyl, azetidinyl, azetidinyl substituted with F, and phenyl substituted with F; and
R 5 is selected from the group consisting of:

19. The compound of claim 1 , and pharmaceutically acceptable salts, solvates, or N—oxides thereof, having the structure of Formula (1C):

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

20. A compound selected from the group consisting of:
8-(7-Chloro-1H-indazol-5-yl)-2-(difluoromethyl)-7-(trifluoromethyl)-[1,2,4]triazolo[1,5-a]pyridine;
7-Chloro-8-(7-methyl-1H-indazol-5-yl)-2-(trifluoromethyl)-[1,2,4]triazolo[1,5-a]pyridine;
6-(2,7-Bis(trifluoromethyl)-[1,2,4]triazolo[1,5-a]pyridin-8-yl)benzo[d]thiazol-2(3H)-one;
2-Cyclobutyl-7-(4-fluorophenyl)-8-(7-methyl-1H-indazol-5-yl)-[1,2,4]triazolo[1,5-a]pyridine;
6-(7-(4-Fluorophenyl)-2-(trifluoromethyl)-[1,2,4]triazolo[1,5-a]pyridin-8-yl)benzo[d]thiazol-2(3H)-one;
7-Cyclopentyl-8-(7-methyl-1H-indazol-5-yl)-2-(trifluoromethyl)-[1,2,4]triazolo[1,5-a]pyridine;
7-(Azetidin-1-yl)-8-(7-methyl-1H-indazol-5-yl)-2-(trifluoromethyl)-[1,2,4]triazolo[1,5-a]pyridine;
7-(3-Fluoroazetidin-1-yl)-8-(7-methyl-1H-indazol-5-yl)-2-(trifluoromethyl)-[1,2,4]triazolo[1,5-a]pyridine;
2-Cyclopentyl-7-(4-fluorophenyl)-8-(7-methyl-1H-indazol-5-yl)-[1,2,4]triazolo[1,5-a]pyridine;
8-(7-Methyl-1H-indazol-5-yl)-2-(trifluoromethyl)-[1,2,4]triazolo[1,5-a]pyridine-7-carbonitrile;
7-Methyl-5-[7-methyl-2-(trifluoromethyl)imidazo[1,2-a]pyridin-8-yl]indolin-2-one;
5-(7-(4-Fluorophenyl)-2-(trifluoromethyl)imidazo[1,2-a]pyridin-8-yl)-1H-indazole;
8-(7-Chloro-1H-indazol-5-yl)-2,7-bis(trifluoromethyl)imidazo[1,2-c]pyrimidine;
8-(7-Chloro-1H-indazol-5-yl)-2-(difluoromethyl)-7-(trifluoromethyl)imidazo[1,2-c]pyrimidine;
2-(Difluoromethyl)-8-(7-methyl-1H-indazol-5-yl)-7-(trifluoromethyl)imidazo[1,2-c]pyrimidine;
8-(7-Methyl-1H-indazol-5-yl)-2-(difluoromethyl)-7-(trifluoromethyl)-[1,2,4]triazolo[1,5-a]pyridine;
7-Chloro-5-(2-(difluoromethyl)-7-(trifluoromethyl)-[1,2,4]triazolo[1,5-a]pyridin-8-yl)indolin-2-one;
7-Methyl-5-(2-(difluoromethyl)-7-(trifluoromethyl)-[1,2,4]triazolo[1,5-a]pyridin-8-yl)indolin-2-one;
8-(7-Chloro-1H-indazol-5-yl)-2,7-bis(trifluoromethyl)-[1,2,4]triazolo[1,5-a]pyridine;
8-(7-Methyl-1H-indazol-5-yl)-2,7-bis(trifluoromethyl)-[1,2,4]triazolo[1,5-a]pyridine;
5-(2,7-Bis(trifluoromethyl)-[1,2,4]triazolo[1,5-a]pyridin-8-yl)-7-chloroindolin-2-one;
5-(2,7-Bis(trifluoromethyl)-[1,2,4]triazolo[1,5-a]pyridin-8-yl)-7-methylindolin-2-one;
8-(7-Chloro-1H-indazol-5-yl)-7-(difluoromethyl)-2-(trifluoromethyl)-[1,2,4]triazolo[1,5-a]pyridine;
8-(7-Methyl-1H-indazol-5-yl)-7-(difluoromethyl)-2-(trifluoromethyl)-[1,2,4]triazolo[1,5-a]pyridine;
7-Chloro-5-(7-(difluoromethyl)-2-(trifluoromethyl)-[1,2,4]triazolo[1,5-a]pyridin-8-yl)indolin-2-one;
7-Methyl-5-(7-(difluoromethyl)-2-(trifluoromethyl)-[1,2,4]triazolo[1,5-a]pyridin-8-yl)indolin-2-one;
7-Methyl-8-(7-methyl-1H-indazol-5-yl)-2-(trifluoromethyl)-[1,2,4]triazolo[1,5-a]pyridine;
7-Ethyl-8-(7-methyl-1H-indazol-5-yl)-2-(trifluoromethyl)-[1,2,4]triazolo[1,5-a]pyridine;
7-Methoxy-8-(7-methyl-1H-indazol-5-yl)-2-(trifluoromethyl)-[1,2,4]triazolo[1,5-a]pyridine;
8-(7-Chloro-1H-indazol-5-yl)-2-cyclopropyl-7-(trifluoromethyl)-[1,2,4]triazolo[1,5-a]pyridine;
2-Cyclopropyl-8-(7-methyl-1H-indazol-5-yl)-7-(trifluoromethyl)-[1,2,4]triazolo[1,5-a]pyridine;
8-(7-Choro-1H-indazol-5-yl)-2-methyl-7

Assignees

• Janssen Pharmaceutica Nv

Inventors

• Ameriks Michael K
• Laforteza Brian Ngo
• Lebold Terry Patrick
• Ravula Suchitra
• Savall Brad M
• Shireman Brock T

Classifications

• A61P9/00

  Drugs for disorders of the cardiovascular system · CPC title

• A61P3/10

  for hyperglycaemia, e.g. antidiabetics · CPC title

• 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

• A61P35/00

  Antineoplastic agents · CPC title