4-piperidin-n-(pyrimidin-4-yl)chroman-7-sulfonamide derivatives as sodium channel inhibitors

Patent metadata

Field	Value
Publication number	US-10793550-B2
Application number	US-201816495802-A
Country	US
Kind code	B2
Filing date	Mar 22, 2018
Priority date	Mar 24, 2017
Publication date	Oct 6, 2020
Grant date	Oct 6, 2020

Abstract

The invention provides 4-piperidin-chroman-7-sulfonamide derivatives and salts thereof that are sodium channel modulators, as well as compositions containing such a compound or salt and therapeutic methods for using such a compound, salt, or composition.

First claim

We claim:

1. A compound selected from the group consisting of:
(S)-6-fluoro-4-((2S,4R)-2-(pyridin-2-yl)-4-(trifluoromethyl)piperidin-1-yl)-N-(pyrimidin-4-yl)chroman-7-sulfonamide;
(S)-6-fluoro-4-((2S,4S)-2-(4-fluorophenyl)-4-hydroxy-4-(trifluoromethyl)piperidin-1-yl)-N-(pyrimidin-4-yl)chroman-7-sulfonamide;
(S)-4-((2S,4R)-4-(difluoromethoxy)-2-(4-fluorophenyl)piperidin-1-yl)-6-fluoro-N-(pyrimidin-4-yl)chroman-7-sulfonamide; and
(S)-6-fluoro-4-((2R,4R)-2-methyl-4-(3-(trifluoromethyl)phenyl)piperidin-1-yl)-N-(pyrimidin-4-yl)chroman-7-sulfonamide;
or a pharmaceutically acceptable thereof.

2. A compound of claim 1 which is:
(S)-6-fluoro-4-((2S,4R)-2-(pyridin-2-yl)-4-(trifluoromethyl)piperidin-1-yl)-N-(pyrimidin-4-yl)chroman-7-sulfonamide, or a pharmaceutically acceptable salt thereof.

3. A compound of claim 1 which is:
(S)-6-fluoro-4-((2S,4S)-2-(4-fluorophenyl)-4-hydroxy-4-(trifluoromethyl)piperidin-1-yl)-N-(pyrimidin-4-yl)chroman-7-sulfonamide, or a pharmaceutically acceptable salt thereof.

4. A compound of claim 1 which is:
(S)-4-((2S,4R)-4-(difluoromethoxy)-2-(4-fluorophenyl)piperidin-1-yl)-6-fluoro-N-(pyrimidin-4-yl)chroman-7-sulfonamide, or a pharmaceutically acceptable salt thereof.

5. A compound of claim 1 which is:
(S)-6-fluoro-4-((2R,4R)-2-methyl-4-(3-(trifluoromethyl)phenyl)piperidin-1-yl)-N-(pyrimidin-4-yl)chroman-7-sulfonamide, or a pharmaceutically acceptable salt thereof.

6. A pharmaceutical composition comprising a compound of claim 1 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient.

7. A pharmaceutical composition comprising the compound of claim 2 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient.

8. A pharmaceutical composition comprising the compound of claim 3 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient.

9. A pharmaceutical composition comprising the compound of claim 4 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient.

10. A pharmaceutical composition comprising the compound of claim 5 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient.

Assignees

• Genentech Inc

Inventors

• Sutherlin Daniel
• Mckerrall Steven
• Lai Kwong Wah

Classifications

• A61P25/24

  Antidepressants · CPC title

• A61P11/00

  Drugs for disorders of the respiratory system · CPC title

• A61P25/02

  for peripheral neuropathies · CPC title

• A61P29/00

  Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID] · CPC title

• A61P9/00

  Drugs for disorders of the cardiovascular system · CPC title