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 A METHOD FOR INCREASING THE SENSITIVITY OF CANCER CELLS TO CHEMOTHERAPY

摘要

1. Substituted amides covered by the general Formula 1! ! where R is 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 hydroxyl,! R21 and R22 are independently selected from the group consisting of hydrogen and optionally substituted lower alkyl,! R16 is selected from the group consisting of hydrogen, cyano, optionally substituted cycloalkyl and optionally substituted lower alkyl,! 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 of claim 1, wherein R is selected from the group consisting of optionally mono-, di- or trisubstituted 4,5,6,7-tetrahydro-benzo [b] thiophen-2-yl, optionally mono-, di or trisubstituted 5,6,7,8-tetrahydro-4H-cyclohepta [b] thiophen-2-yl, optionally mono-, di- or trisubstituted pyrazin-2-yl, where the substituents are independently selected from lower alkyls, and mono-, di- or trisubstituted phenyl, where the substituents are independently selected from heterocycloalkyl, cycloalkyl-substituted lower alkyl, hydroxy, lower alkyl, sulfonyl