Inhibitors of bruton's tyrosine kinase

Patent metadata

Field	Value
Publication number	US-10093657-B2
Application number	US-201715454452-A
Country	US
Kind code	B2
Filing date	Mar 9, 2017
Priority date	Dec 13, 2013
Publication date	Oct 9, 2018
Grant date	Oct 9, 2018

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 method for treating an inflammatory and/or autoimmune condition, comprising a step of administering to a patient in need thereof a therapeutically effective amount of a compound of Formula I:

wherein:
R 1 is H or halo;
R 2 is H, halo, 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 lower alkyl or halo;
or a pharmaceutically acceptable salt thereof.

2. A method for treating an inflammatory condition, comprising a step of administering to a patient in need thereof a therapeutically effective amount of a compound of Formula I:

wherein:
R 1 is H or halo;
R 2 is H, halo, 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 lower alkyl or halo;
or a pharmaceutically acceptable salt thereof.

Assignees

• Hoffmann La Roche
• Chugai Pharmaceutical Inc
• Chugai Pharmaceutical Co Ltd

Inventors

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

Classifications

• 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

• A61P43/00

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

• A61P37/06

  Immunosuppressants, e.g. drugs for graft rejection · CPC title

• A61P7/04

  Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents · CPC title

• A61P9/00

  Drugs for disorders of the cardiovascular system · CPC title