Patent ID: 8563563

Claim:
A method for treating a B-cell proliferative disorder 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 an anti-cancer drug, wherein the irreversible 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 alkyl, optionally substituted or unsubstituted cycloalkyl, optionally substituted or unsubstituted alkenyl, optionally substituted or unsubstituted alkynyl; 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 —, heteroaryl, aryl, —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 alkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, 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; each R 9 is independently 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 11 and R 10 can together form a 5-, 6-, 7-, or 8-membered heterocyclic ring; and each R 11 is independently selected from H, —S(═O) 2 R 8 , —S(═O) 2 NH 2 , —C(O)R 8 , —CN, —NO 2 , heteroaryl, or heteroalkyl; or pharmaceutically acceptable salts thereof.