Inhibitors of bruton's tyrosine kinase

A method of treating a mast cell proliferative disorder, comprising administering to a patient in need thereof a therapeutically effective amount of a compound that irreversibly inhibits an interleukin-2 inducible tyrosine kinase (ITK) having the structure of Formula (A1)

• wherein:
• A is N;
• R1 is L2-(substituted or unsubstituted heteroaryl), or L2-(substituted or unsubstituted aryl), where L2 is a bond, O, S, —S(═O), —S(═O)2, C(═O), -(substituted or unsubstituted C1-C6 alkylene), or -(substituted or unsubstituted C2-C6 alkenylene);
• R2 and R3 are independently selected from H or lower alkyl;
• R4 is L3-X-L4-G, wherein,
• L3 is optional, and when present is a bond, or an optionally substituted group selected from alkylene, heteroalkylene, arylene, heteroarylene, alkylarylene, alkylheteroarylene, and alkylheterocycloalkylene;
• X is optional, and when present is a bond, O, —C(═O), S, —S(═O), —S(═O)2, —NH, —NR9, —NHC(O), —C(O)NH, —NR9C(O), —C(O)NR9, —S(═O)2NH, —NHS(═O)2, —S(═O)2NR9—, —NR9S(═O)2, —OC(O)NH—, —NHC(O)O—, —OC(O)NR9—, —NR9C(O)O—, —CH═NO—, —ON═CH—, —NR10C(O)NR10—, heteroarylene, arylene, —NR10C(═NR11)NR10—, —NR10C(═NR11)—, —C(═NR11)NR10—, —OC(═NR11)—, or —C(═NR11)O—;
• L4 is optional, and when present is a bond, 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 heterocyclene;
• or L3, X and L4 taken together form a nitrogen containing heterocyclic ring;
• G is
• wherein,
• Ra is H, substituted or unsubstituted alkyl, or substituted or unsubstituted cycloalkyl;
• R7 and R8 are H;
• and 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-C8alkylether, C1-C8alkylamide, or C1-C4alkyl(C2-C8heterocycloalkyl);
• or
• R6 and R8 are H;
• and 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-C8alkylether, C1-C8alkylamide, or C1-C4alkyl(C2-C8heterocycloalkyl);
• or
• R7 and R8 taken together form a bond;
• and R6 is H, substituted or unsubstituted C1-C4alkyl, substituted or unsubstituted C1-C4heteroalkyl, Ci-Cgalkylaminoalkyl, C1-C8hydroxyalkylaminoalkyl, Ci-Cgalkoxyalkylaminoalkyl, 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-C8alkylether, C1-C8alkylamide, or C1-C4alkyl(C2-C8heterocycloalkyl);
• R9 is selected from among H, substituted or unsubstituted lower alkyl, and substituted or unsubstituted lower cycloalkyl;
• each R10 is independently H, substituted or unsubstituted lower alkyl, or substituted or unsubstituted lower cycloalkyl;
• or
• two R10 groups can together form a 5-, 6-, 7-, or 8-membered heterocyclic ring;
• or
• R10 and R11 can together form a 5-, 6-, 7-, or 8-membered heterocyclic ring;
• or
• R11 is selected from H, —S(═O)2R8, —S(═O)2NH2, —C(O)R8, —CN, —NO2, heteroaryl, or heteroalkyl;
• or a pharmaceutically acceptable solvate, hydrate, or salt thereof.