Acyl sulfonamide NaV1.7 inhibitors

Patent metadata

Field	Value
Publication number	US-10836758-B2
Application number	US-201716344414-A
Country	US
Kind code	B2
Filing date	Oct 26, 2017
Priority date	Oct 27, 2016
Publication date	Nov 17, 2020
Grant date	Nov 17, 2020

Abstract

The present disclosure relates to compounds of formula I which inhibit NaV1.7, and include pharmaceutically acceptable salts, compositions comprising such compounds, and methods using and making such compounds and compositions. (I)

First claim

We claim:

1. A compound of formula I

where:
A is N(R 4 )(R 5 );
R 1 is thiazolyl or thiadiazolyl and is substituted with 0-2 substituents selected from cyano, halo, alkyl, haloalkyl, alkoxy, and haloalkoxy;
R 2 is cyano, halo, alkyl, haloalkyl, alkoxy, or haloalkoxy;
R 3 is cyano, halo, alkyl, haloalkyl, alkoxy, or haloalkoxy;
R 4 is a [1-4.1-4.0-2] bridged bicyclicamine with 0-3 halo or alkyl substituents;
R 5 is hydrogen or alkyl;
or NR 4 R 5 taken together is azetidinyl, pyrrolidinyl, piperidinyl, piperidinonyl, piperazinyl, or morpholinyl, and is substituted with 0-1 NR 6 R 7 substituent and also with 0-5 halo or alkyl substituents;
or NR 4 R 5 taken together is a [1-4.1-4.0-2]bridged bicyclicdiamine with 0-3 halo or alkyl substituents;
R 6 is hydrogen, alkyl, or cycloalkyl;
R 7 is hydrogen, alkyl, or cycloalkyl;
or NR 6 R 7 taken together is azetidinyl, pyrrolidinyl, piperidinyl, piperidinonyl, piperazinyl, or morpholinyl, and is substituted with 0-5 halo, hydroxyl, alkyl, hydroxyalkyl, or alkoxyalkyl substituents;
or NR 6 R 7 taken together is oxaazaspirodecanyl; and
Ar 1 is phenyl substituted with 0-5 substituents selected from cyano, halo, alkyl, haloalkyl, alkoxy, and haloalkoxy;
or a pharmaceutically acceptable salt thereof.

2. A compound of claim 1 where R 1 is thiazolyl or thiadiazolyl.

3. A compound of claim 1 where R 2 and R 3 are halo.

4. A compound of claim 1 selected from the group consisting of
5-chloro-2-fluoro-4-((octahydrocyclopenta[c]pyrrol-4-yl)amino)-N-(thiazol-2-yl)benzenesulfonamide;
4-([3,4′-bipiperidin]-1-yl)-5-chloro-2-fluoro-N-(thiazol-2-yl)benzenesulfonamide;
5-chloro-2-fluoro-4-(octahydro-2,7-naphthyridin-2(1H)-yl)-N-(thiazol-2-yl)benzenesulfonamide;
5-chloro-2-fluoro-4-(3-(methoxymethyl)pyrrolidin-1-yl)-N-(thiazol-2-yl)benzenesulfonamide; and
5-chloro-2-fluoro-4-(3-(hydroxymethyl)pyrrolidin-1-yl)-N-(thiazol-2-yl)benzenesulfonamide;
or a pharmaceutically acceptable salt thereof.

5. A pharmaceutical composition comprising a therapeutically effective amount of a compound of claim 1 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

6. A method for treating pain in a patient comprising administering a therapeutically effective amount of a compound of claim 1 , or a pharmaceutically acceptable salt thereof, with a pharmaceutically acceptable carrier.

Assignees

• Bristol Myers Squibb Co

Inventors

• Wu Yong-Jin
• Guernon Jason M

Classifications

• A61P25/04

  Centrally acting analgesics, e.g. opioids · CPC title

• C07D417/12 Primary

  linked by a chain containing hetero atoms as chain links · CPC title

• A61K31/4439

  containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole (nicotine A61K31/465) · CPC title

• C07D285/06

  1,2,3-Thiadiazoles; Hydrogenated 1,2,3-thiadiazoles · CPC title

• A61P43/00

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