Substituted benzamides and methods of use thereof

Patent metadata

Field	Value
Publication number	US-9546164-B2
Application number	US-201514603273-A
Country	US
Kind code	B2
Filing date	Jan 22, 2015
Priority date	Nov 27, 2013
Publication date	Jan 17, 2017
Grant date	Jan 17, 2017

Abstract

The invention provides compounds having the general formula I:

and pharmaceutically acceptable salts thereof, wherein the variables R A , R AA , subscript n, ring A, X 2 , L, subscript m, X 1 , R 1 , R 2 , R 3 , R 4 , R 5 , and R N have the meaning as described herein, and compositions containing such compounds and methods for using such compounds and compositions.

First claim

The invention claimed is:

1. A compound selected from the group consisting of:

(R)—N-(azetidin-1-ylsulfonyl)-4-((1-(2-chloro-4-fluorobenzyl)piperidin-3-yl)oxy)-5-cyclopropyl-2-fluorobenzamide,

(S)-5-cyclopropyl-4-((1-(1-(3,5-dichlorophenyl)ethyl)piperidin-4-yl)methoxy)-2-fluoro-N-(methylsulfonyl)benzamide,

(S)-5-cyclopropyl-4-((1-(1-(3,5-dichlorophenyl)-2-methoxyethyl)piperidin-4-yl)methoxy)-N-(ethylsulfonyl)-2-fluorobenzamide,

(S)-5-cyclopropyl-N-(cyclopropylsulfonyl)-4-((1-(1-(3,5-dichlorophenyl)ethyl)piperidin-4-yl)methoxy)-2-fluorobenzamide,

(S)-4-((1-(1-(3-chloro-5-(trifluoromethyl)phenyl)ethyl)piperidin-4-yl)methoxy)-5-cyclopropyl-2-fluoro-N-(methylsulfonyl)benzamide,

4-(((R)-1-((R)-1-(5-chloro-6-cyclopropylpyridin-2-yl)ethyl)piperidin-3-yl)oxy-5-cyclopropyl-2-fluoro-N-(methylsulfonyl)benzamide,

(R)-4-((1-(2-chloro-4-fluorobenzyl)piperidin-3-yl)oxy)-5-cyclopropyl-2-fluoro-N-(methylsulfonyl)benzamide,

4-((1-(3-chloro-2-fluoro-5-(trifluoromethyl)benzyl)-4-fluoropiperidin-4-yl)methoxy)-5-cyclopropyl-2-fluoro-N-(methylsulfonyl)benzamide, and

4-((1-(3-fluorobenzyl)piperidin-4-yl)methoxy)-5-cyclopropyl-2-fluoro-N-(methylsulfonyl)benzamide,
and pharmaceutically acceptable salts thereof.

2. The compound of claim 1 which is:

(R)—N-(azetidin-1-ylsulfonyl)-4-((1-(2-chloro-4-fluorobenzyl)piperidin-3-yl)oxy)-5-cyclopropyl-2-fluorobenzamide or a pharmaceutically acceptable salt thereof.

3. The compound of claim 1 which is:

(S)-5-cyclopropyl-4-((1-(1-(3,5-dichlorophenyl)ethyl)piperidin-4-yl)methoxy)-2-fluoro-N-(methylsulfonyl)benzamide or a pharmaceutically acceptable salt thereof.

4. The compound of claim 1 which is:

(S)-5-cyclopropyl-4-((1-(1-(3,5-dichlorophenyl)-2-methoxyethyl)piperidin-4-yl)methoxy)-N-(ethylsulfonyl)-2-fluorobenzamide or a pharmaceutically acceptable salt thereof.

5. The compound of claim 1 which is:

(S)-5-cyclopropyl-N-(cyclopropylsulfonyl)-4-((1-(1-(3,5-dichlorophenyl)ethyl)piperidin-4-yl)methoxy)-2-fluorobenzamide or a pharmaceutically acceptable salt thereof.

6. The compound of claim 1 which is:

(S)-4-((1-(1-(3-chloro-5-(trifluoromethyl)phenyl)ethyl)piperidin-4-yl)methoxy)-5-cyclopropyl-2-fluoro-N-(methylsulfonyl)benzamide or a pharmaceutically acceptable salt thereof.

7. The compound of claim 1 which is:

4-(((R)-1-((R)-1-(5-chloro-6-cyclopropylpyridin-2-yl)ethyl)piperidin-3-yl)oxy)-5-cyclopropyl-2-fluoro-N-(methylsulfonyl)benzamide or a pharmaceutically acceptable salt thereof.

8. The compound of claim 1 which is:

(R)-4-((1-(2-chloro-4-fluorobenzyl)piperidin-3-yl)oxy)-5-cyclopropyl-2-fluoro-N-(methylsulfonyl)benzamide or a pharmaceutically acceptable salt thereof.

9. The compound of claim 1 which is:

4-((1-(3-chloro-2-fluoro-5-(trifluoromethyl)benzyl)-4-fluoropiperidin-4-yl)methoxy)-5-cyclopropyl-2-fluoro-N-(methylsulfonyl)benzamide or a pharmaceutically acceptable salt thereof.

10. The compound of claim 1 which is:

4-((1-(3-fluorobenzyl)piperidin-4-yl)methoxy)-5-cyclopropyl-2-fluoro-N-(methylsulfonyl)benzamide or a pharmaceutically acceptable salt thereof.

11. The compound of claim 1 which is:

(R)—N-(azetidin-1-ylsulfonyl)-4-((1-(2-chloro-4-fluorobenzyl)piperidin-3-yl)oxy)-5-cyclopropyl-2-fluorobenzamide.

12. The compound of claim 1 which is:

(S)-5-cyclopropyl-4-((1-(1-(3,5-dichlorophenyl)ethyl)piperidin-4-yl)methoxy)-2-fluoro-N-(methylsulfonyl)benzamide.

13. The compound of claim 1 which is:

(S)-5-cyclopropyl-4-((1-(1-(3,5-dichlorophenyl)-2-methoxyethyl)piperidin-4-yl)methoxy)-N-(ethylsulfonyl)-2-fluorobenzamide.

14. The compound of claim 1 which is:

(S)-5-cyclopropyl-N-(cyclopropylsulfonyl)-4-((1-(1-(3,5-dichlorophenyl)ethyl)piperidin-4-yl)methoxy)-2-fluorobenzamide.

15. The compound of claim 1 which is:

(S)-4-((1-(1-(3-chloro-5-(trifluoromethyl)phenyl)ethyl)piperidin-4-yl)methoxy)-5-cyclopropyl-2-fluoro-N-(methylsulfonyl)benzamide.

16. The compound of claim 1 which is:

4-(((R)-1-((R)-1-(5-chloro-6-cyclopropylpyridin-2-yl)ethyl)piperidin-3-yl)oxy)-5-cyclopropyl-2-fluoro-N-(methylsulfonyl)benzamide.

17. The compound of claim 1 which is:

(R)-4-((1-(2-chloro-4-fluorobenzyl)piperidin-3-yl)oxy)-5-cyclopropyl-2-fluoro-N-(methylsulfonyl)benzamide.

18. The compound of claim 1 which is:

4-((1-(3-chloro-2-fluoro-5-(trifluoromethyl)benzyl)-4-fluoropiperidin-4-yl)methoxy)-5-cyclopropyl-2-fluoro-N-(methylsulfonyl)benzamide.

19. The compound of claim 1 which is:

4-((1-(3-fluorobenzyl)piperidin-4-yl)methoxy)-5-cyclopropyl-2-fluoro-N-(methylsulfonyl)benzamide.

20. A pharmaceutical composition co

Assignees

• Genentech Inc
• Xenon Pharmaceuticals Inc

Inventors

• Andrez Jean-Christophe
• Bichler Paul Robert
• Chen Chien-An
• Chowdhury Sultan
• Decker Shannon Marie
• Dehnhardt Christoph Martin
• Focken Thilo
• Grimwood Michael Edward
• Hemeon Ivan William
• Jia Qi
• Li Jun
• Liu Zhiguo
• Ortwine Daniel F
• Safina Brian
• Sutherlin Daniel
• Sheng Tao
• Sun Shaoyi
• White Andrew D
• Wilson Michael Scott
• Zenova Alla Yurevna
• Zhu Jiuxiang

Classifications

• A61P9/00

  Drugs for disorders of the cardiovascular system · CPC title

• A61P35/00

  Antineoplastic agents · 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

• A61P31/18

  for HIV · CPC title

• A61P25/06

  Antimigraine agents · CPC title