INHIBITORS OF BRUTON'S TYROSINE KINASE FOR THE TREATMENT OF SOLID TUMORS

摘要

Described herein are irreversible Btk inhibitor compounds, and methods for using such irreversible inhibitors in the treatment of diseases and disorders characterized by the presence or development of solid tumors.

主权项

1. A method for treating HER2 amplified breast cancer in an individual in need thereof comprising administering to an individual in need thereof a composition comprising a therapeutically-effective amount of a compound of Formula (C1) having the structure:wherein:
Y is an optionally substituted group selected from among alkyl, heteroalkyl, aryl, heteroaryl, alkylaryl, alkylheteroaryl, and alkylheterocycloalkyl; R12 is H or lower alkyl; or Y and R12 taken together form a 4-, 5-, or 6-membered heterocyclic ring; G is  where Ra is H, substituted or unsubstituted alkyl, substituted or unsubstituted cycloalkyl; and either R7 and R8 are H;
R6 is H, substituted or unsubstituted C1-C4alkyl, substituted or unsubstituted C1-C4heteroalkyl, C1-C8alkylaminoalkyl, C1-C8hydroxyalkylaminoalkyl, C1-C8alkoxyalkylaminoalkyl, substituted or unsubstituted C3-C6cycloalkyl, substituted or unsubstituted C1-C8alkylC3-C6cycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted C2-C8heterocycloalkyl, substituted or unsubstituted heteroaryl, C1-C4alkyl(aryl), C1-C4alkyl(heteroaryl), C1-C8alkylethers, C1-C8alkylamides, or C1-C4alkyl(C2-C8heterocycloalkyl); R6 and R8 are H;
R7 is H, substituted or unsubstituted C1-C4alkyl, substituted or unsubstituted C1-C4heteroalkyl, C1-C8alkylaminoalkyl, C1-C8hydroxyalkylaminoalkyl, C1-C8alkoxyalkylaminoalkyl, substituted or unsubstituted C3-C6cycloalkyl, substituted or unsubstituted C1-C8alkylC3-C6cycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted C2-C8heterocycloalkyl, substituted or unsubstituted heteroaryl, C1-C4alkyl(aryl), C1-C4alkyl(heteroaryl), C1-C8alkylethers, C1-C8alkylamides, or C1-C4alkyl(C2-C8heterocycloalkyl); or R7 and R8 taken together form a bond;
R6 is H, substituted or unsubstituted C1-C4alkyl, substituted or unsubstituted C1-C4heteroalkyl, C1-C8alkylaminoalkyl, C1-C8hydroxyalkylaminoalkyl, C1-C8alkoxyalkylaminoalkyl, substituted or unsubstituted C3-C6cycloalkyl, substituted or unsubstituted C1-C8alkylC3-C6cycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted C2-C8heterocycloalkyl, substituted or unsubstituted heteroaryl, C1-C4alkyl(aryl), C1-C4alkyl(heteroaryl), C1-C8alkylethers, C1-C8alkylamides, or C1-C4alkyl(C2-C8heterocycloalkyl).