Substituted amides, pharmaceutical compositions containing them, a method for inhibiting ATP hydrolysis, METHOD FOR INHIBITING ACTIVITY OF B-CELLS, METHOD FOR DETERMINING Btk in a sample, method of treating diseases responsive to inhibition of Btk ACTIVITY, AND METHOD FOR INCREASING THE SENSITIVITY OF CANCER CELLS TO CHEMOTHERAPY

摘要

1. Substituted amides covered by the general Formula 1:! ! where R is an optionally substituted aryl or optionally substituted heteroaryl,! R4 is selected from the group consisting of hydrogen, optionally substituted lower alkyl, optionally substituted lower alkoxy, halogen and hydroxy,! R21 and R22 are independently selected from hydrogen and optionally substituted lower alkyl,! R16 is selected from the group consisting of hydrogen, cyano, optionally substituted cycloalkyl and optionally substituted lower alkyl,! And selected from the group consisting of optionally substituted 5-membered heteroaryl, optionally substituted pyridazinyl, optionally substituted pyrimidinyl and optionally substituted pyrazinyl,! L is selected from the group consisting of optionally substituted C0-C4 alkylene, -O-optionally substituted C0-C4 alkylene, - (C0-C4 alkylene) (SO) -, - (C0-C4 alkylene) (SO2) - and - (C0-C4 alkylene) ( C = O) -, ah! G is selected from the group consisting of hydrogen, halogen, hydroxy, alkoxy, nitro, optionally substituted alkyl, optionally substituted amino, optionally substituted carbamimidoyl, optionally substituted heterocycloalkyl, optionally substituted cycloalkyl, optionally substituted aryl and optionally substituted heteroaryl; ! and their pharmaceutically acceptable salts, solvates, chelates, non-covalent complexes, prodrugs and mixtures. ! 2. The substituted amides according to claim 1, in which R is selected from the group consisting of optionally mono-, di- or tri-substituted 4,5,6,7-tetrahydrobenzo [b] thiophen-2-yl, where the substituents are independently selected from lower alkyl, optionally mono-, di- or tri-substituted 5,6,7,8-tetrahydro-4H-cyclohepta [b] thiophen-2-yl, where the substituents are independently selected