Patent ID: 8658653

Claim:
A method for treating a B-cell malignancy in a subject in need thereof comprising administering to the subject two or more agents, wherein the first agent is an irreversible inhibitor of Bruton's tyrosine kinase (Btk) and the second agent is selected from paclitaxel, amrubicin, or azacitidine, wherein the irreversible Btk inhibitor is a compound having the structure of Formula (A): wherein: A is N; R 1 is phenyl-O-phenyl or phenyl-S-phenyl; R 2 and R 3 are independently H; R 4 is L 3 -X-L 4 -G, wherein, L 3 is optional, and when present is an optionally substituted or unsubstituted alkylene, optionally substituted or unsubstituted cycloalkylene, optionally substituted or unsubstituted alkenylene, or optionally substituted or unsubstituted alkynylene; X is optional, and when present is O, —C(═O), S, —S(═O), —S(═O) 2 , —NH, —NR 9 , —NHC(O), —C(O)NH, —NR 9 C(O), —C(O)NR 9 , —S(═O) 2 NH, —NHS(═O) 2 , —S(═O) 2 NR 9 —, —NR 9 S(═O) 2 , —OC(O)NH—, —NHC(O)O—, —OC(O)NR 9 —, —NR 9 C(O)O—, —CH═NO—, —ON═CH—, —NR 10 C(O)NR 10 —, heteroarylene, arylene, —NR 10 C(═NR 11 )NR 10 —, —NR 10 C(═NR 11 )—, —C(═NR 11 )NR 10 —, —OC(═NR 11 )—, or —C(═NR 11 )O—; L 4 is optional, and when present is a substituted or unsubstituted alkylene, substituted or unsubstituted cycloalkylene, substituted or unsubstituted alkenylene, substituted or unsubstituted alkynylene, substituted or unsubstituted arylene, substituted or unsubstituted heteroarylene, or substituted or unsubstituted heterocycle; or L 3 , X and L 4 taken together form a nitrogen containing heterocyclic ring; G is wherein, R 6 , R 7 and R 8 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; R 9 is selected from among H, substituted or unsubstituted lower alkyl, and substituted or unsubstituted lower cycloalkyl; each R 10 is independently H, substituted or unsubstituted lower alkyl, or substituted or unsubstituted lower cycloalkyl; or two R 10 groups can together form a 5-, 6-, 7-, or 8-membered heterocyclic ring; or R 10 and R 11 can together form a 5-, 6-, 7-, or 8-membered heterocyclic ring; and R 11 is selected from H, —S(═O) 2 R 8 , —S(═O) 2 NH 2 , —C(O)R 8 , —CN, —NO 2 , heteroaryl, or heteroalkyl; or a pharmaceutically acceptable salt thereof.