Patent ID: 8883435
Filing Date: 2014-11-11
Classification: A61K,A61P,C07D,C07K

Abstract:
1. A method of identifying an irreversible inhibitor of a Bruton's tyrosine kinase (Btk) comprising: (1) contacting Btk with a compound of Formula VII; (2) contacting at least one non-kinase molecule having at least one accessible SH group including glutathione and/or hemoglobin with the compound of Formula VII; and (3) determining the covalent binding of the compound of Formula VII with Btk and the at least one non-kinase molecule; and repeating steps (1), (2), and (3) for at least one other compound of Formula VII, wherein the compound of Formula (VII) has the structure: wherein: is a moiety that binds to the active site of a Btk kinase; Y is an optionally substituted group selected from among alkylene, heteroalkylene, arylene, heteroarylene, heterocycloalkylene, cycloalkylene, alkylenearylene, alkyleneheteroarylene, alkylenecycloalkylene, and alkyleneheterocycloalkylene; Z is C(═O), OC(═O), NHC(═O), NCH R R R wherein a desired irreversible inhibitor is selective for Btk relative to glutathione and hemoglobin.