Inhibitors of bruton's tyrosine kinase

Patent metadata

Field	Value
Publication number	US-11104668-B2
Application number	US-201416815443-A
Country	US
Kind code	B2
Filing date	Dec 10, 2014
Priority date	Dec 13, 2013
Publication date	Aug 31, 2021
Grant date	Aug 31, 2021

Abstract

This application discloses compounds according to generic Formula (I): wherein all variables are defined as described herein, which inhibit Btk. The compounds disclosed herein are useful to modulate the activity of Btk and treat diseases associated with excessive Btk activity. The compounds are useful for the treatment of oncological, auto-immune, and inflammatory diseases caused by aberrant B-cell activation. Also disclosed are compositions containing compounds of Formula (I) and at least one carrier, diluent or excipient.

First claim

The invention claimed is:

1. A compound of Formula I:

wherein:
R 1 is H or F;
R 2 is H, F, or cyano;
R 3 is R 4 or R 5 ;
R 4 is halo or cyano;
R 5 is phenyl, heteroaryl, —C(═O)R 5′ , lower alkyl, or benzyl, optionally substituted with one or more R 5′ ;
R 5′ is lower alkyl, cyano, hydroxyl, heterocycloalkyl, phenyl, amino, alkyl amino, dialkyl amino, or lower alkoxy; and

X is methyl;
or a pharmaceutically acceptable salt thereof.

2. The compound of claim 1 , wherein R 5 is thiophenyl, optionally substituted with one or more R 5′ .

3. The compound of claim 1 , wherein R 5 is pyridyl, optionally substituted with one or more R 5′ .

4. The compound of claim 1 , wherein R 1 is F and R 2 is F.

5. The compound of claim 1 , wherein R 1 is H and R 2 is cyano.

6. The compound of claim 1 , wherein R 5 is —C(═O)R 5′ .

7. The compound of claim 1 , wherein R 5′ is morpholinyl, piperidinyl, lower alkyl piperidinyl, or lower alkoxy.

8. The compound of claim 1 , wherein R 5 is phenyl or benzyl, optionally substituted with one or more R 5′ .

9. The compound of claim 1 , wherein R 5 is lower alkyl, optionally substituted with one or more R 5′ .

10. A pharmaceutical composition, comprising a therapeutically effective amount of a compound according to claim 1 , or a pharmaceutically acceptable salt thereof, admixed with at least one pharmaceutically acceptable carrier, excipient or diluent.

11. A method for treating an autoimmune condition, comprising the step of administering to a patient in need thereof a therapeutically effective amount of a compound according to claim 1 , or a pharmaceutically acceptable salt thereof.

12. A method for treating an inflammatory condition, comprising the step of administering to a patient in need thereof a therapeutically effective amount of a compound according to claim 1 , or a pharmaceutically acceptable salt thereof.

13. A method for treating rheumatoid arthritis, comprising the step of administering to a patient in need thereof a therapeutically effective amount of a compound according to claim 1 , or a pharmaceutically acceptable salt thereof.

14. A method for treating asthma, comprising the step of administering to a patient in need thereof a therapeutically effective amount of a compound according to claim 1 , or a pharmaceutically acceptable salt thereof.

Assignees

• Hoffmann La Roche
• Chugai Pharmaceutical Co Ltd

Inventors

• Lopez-Tapia Francisco Javier
• So Sung-Sau
• Qiao Qi
• Dominique Romyr

Classifications

• C07D409/14

  containing three or more hetero rings · CPC title

• C07D403/14

  containing three or more hetero rings · CPC title

• C07D403/06 Primary

  linked by a carbon chain containing only aliphatic carbon atoms · CPC title

• A61K31/5377

  not condensed and containing further heterocyclic rings, e.g. timolol · CPC title

• A61K31/496

  Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin · CPC title