N-substituted benzamides and methods of use thereof

Patent metadata

Field	Value
Publication number	US-9771376-B2
Application number	US-201615133030-A
Country	US
Kind code	B2
Filing date	Apr 19, 2016
Priority date	May 22, 2000
Publication date	Sep 26, 2017
Grant date	Sep 26, 2017

Abstract

The invention provides novel compounds having the general formula:

and pharmaceutically acceptable salts thereof, wherein the variables R A , subscript n, ring A, X 2 , L, subscript m, X 1 , B, 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

We claim:

1. A method of treating pain in a mammal having pain comprising administering to the mammal a therapeutically effective amount of a compound selected from:
4-(adamantan-1-ylmethoxy)-5-chloro-2-fluoro-N-(methylsulfonyl)benzamide
4-(1-adamantylmethoxy)-3-cyclopropyl-N-methylsulfonyl-benzamide
4-(1-adamantylmethoxy)-5-cyclopropyl-2-fluoro-N-(2-methoxyethylsulfonyl)benzamide
4-(1-adamantylmethoxy)-5-cyclopropyl-2-fluoro-N-(3-fluoroazetidin- 1-yl)sulfonyl-benzamide
4-(1-adamantylmethoxy)-N-(azetidin-1-ylsulfonyl)-5-cyclopropyl-2-fluoro-benzamide
4-(2-adamantyloxymethyl)-5-chloro-2-fluoro-N-methylsulfonyl-benzamide
4-(1-adamantylmethoxy)-5-cyclopropyl-2-fluoro-N-morpholinosulfonylbenzamide
4-(1-adamantylmethoxy)-5-cyclopropyl-N-ethylsulfonyl-2-fluoro-benzamide; and
cyclopropanesulfonic acid 4-(bicyclo[4.1.0]hept-1-ylmethoxy)-5-cyclopropyl-2-fluorobenzoylamide;
or a pharmaceutically acceptable salt thereof.

2. The method of claim 1 , wherein the compound is 4-(adamantan-1-ylmethoxy)-5-chloro-2-fluoro-N-(methylsulfonyl)benzamide.

3. The method of claim 1 , wherein the compound is 4-(1-adamantylmethoxy)-3-cyclopropyl-N-methylsulfonyl-benzamide.

4. The method of claim 1 , wherein the compound is 4-(1-adamantylmethoxy)-5-cyclopropyl-2-fluoro-N-(2-methoxyethylsulfonyl)benzamide.

5. The method of claim 1 , wherein the compound is 4-(1-adamantylmethoxy)-5-cyclopropyl-2-fluoro-N-(3-fluoroazetidin-1-yl)sulfonyl-benzamide.

6. The method of claim 1 , wherein the compound is 4-(1-adamantylmethoxy)-N-(azetidin-1-ylsulfonyl)-5-cyclopropyl-2-fluoro-benzamide.

7. The method of claim 1 , wherein the compound is 4-(2-adamantyloxymethyl)-5-chloro-2-fluoro-N-methylsulfonyl-benzamide.

8. The method of claim 1 , wherein the compound is 4-(1-adamantylmethoxy)-5-cyclopropyl-2-fluoro-N-morpholinosulfonylbenzamide.

9. The method of claim 1 , wherein the compound is 4-(1-adamantylmethoxy)-5-cyclopropyl-N-ethylsulfonyl-2-fluoro-benzamide.

10. The method of claim 1 , wherein the compound is cyclopropanesulfonic acid 4-(bicyclo[4.1.0]hept-1-ylmethoxy)-5-cyclopropyl-2-fluorobenzoylamide.

11. The method of claim 1 , wherein a pharmaceutically acceptable salt of 4-(adamantan-1-ylmethoxy)-5-chloro-2-fluoro-N-(methylsulfonyl)benzamide is administered.

12. The method of claim 1 , wherein a pharmaceutically acceptable salt of 4-(1-adamantylmethoxy)-3-cyclopropyl-N-methylsulfonyl-benzamide is administered.

13. The method of claim 1 , wherein a pharmaceutically acceptable salt of 4-(1-adamantylmethoxy)-5-cyclopropyl-2-fluoro-N-(2-methoxyethylsulfonyl)benzamide.

14. The method of claim 1 , wherein a pharmaceutically acceptable salt of 4-(1-adamantylmethoxy)-5-cyclopropyl-2-fluoro-N-(3-fluoroazetidin-1-yl)sulfonyl-benzamide is administered.

15. The method of claim 1 , wherein a pharmaceutically acceptable salt of 4-(1-adamantylmethoxy)-N-(azetidin-1-yl sulfonyl)-5-cyclopropyl-2-fluoro-benzamide is administered.

16. The method of claim 1 , wherein a pharmaceutically acceptable salt of 4-(2-adamantyloxymethyl)-5-chloro-2-fluoro-N-methylsulfonyl-benzamide is administered.

17. The method of claim 1 , wherein a pharmaceutically acceptable salt of 4-(1-adamantylmethoxy)-5-cyclopropyl-2-fluoro-N-morpholinosulfonylbenzamide is administered.

18. The method of claim 1 , wherein a pharmaceutically acceptable salt of 4-(1-adamantylmethoxy)-5-cyclopropyl-N-ethylsulfonyl-2-fluoro-benzamide is administered.

19. The method of claim 1 , wherein a pharmaceutically acceptable salt of cyclopropanesulfonic acid 4-(bicyclo[4.1.0]hept-1-ylmethoxy)-5-cyclopropyl-2-fluorobenzoylamide is administered.

Assignees

• Genentech Inc
• Xenon Pharmaceuticals Inc

Inventors

• Chowdhury Sultan
• Dehnhardt Christoph Martin
• Focken Thilo
• Grimwood Michael Edward
• Hemeon Ivan William
• Jia Qi
• Ortwine Daniel F
• Safina Brian
• Sun Shaoyi
• Sutherlin Daniel P
• Zenova Alla Yurevna

Classifications

• A61P9/00

  Drugs for disorders of the cardiovascular system · CPC title

• A61P43/00

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

• A61P25/02

  for peripheral neuropathies · CPC title