Inhibitors of Bruton'S tyrosine kinase

摘要

Described herein are irreversible kinase inhibitor compounds exemplified by the following structure Formula (B2):;
methods for synthesizing such irreversible inhibitors, and methods for using such irreversible inhibitors in the treatment of a B cell proliferative disorder or a mast cell proliferative disorder.

主权项

1. A compound of Formula (B5) having the structure:wherein:
Y is a 4-, 5-, 6-membered cycloalkylene ring; each Ra is independently H, halogen, —CF3, —CN, —NO2, OH, NH2, -La-(substituted or unsubstituted alkyl), -La-(substituted or unsubstituted alkenyl), -La-(substituted or unsubstituted heteroaryl), or -La-(substituted or unsubstituted aryl), wherein La is a bond, O, S, —S(═O), —S(═O)2, NH, C(O), CH2, —NHC(O)O, —NHC(O), or —C(O)NH; G is R2 is selected from H, lower alkyl, and substituted lower alkyl; R6, R7 and R8 are independently selected from among H, lower alkyl or substituted lower alkyl, lower heteroalkyl or substituted lower heteroalkyl, substituted or unsubstituted lower cycloalkyl, and substituted or unsubstituted lower heterocycloalkyl; R12 is H or lower alkyl; or Y and R12 taken together form a 4-, 5-, or 6-membered heterocyclic ring; or pharmaceutically acceptable salts thereof.