主权项 |
1. A method of treating a blood cell cancer comprising administering to a subject in need thereof a composition containing a therapeutically effective amount of an inhibitor of a tyrosine kinase, wherein the tyrosine kinase is interleukin-2-inducible tyrosine kinase (ITK) or Bruton's tyrosine kinase wherein the inhibitor has the structure of Formula (A): 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, lower alkyl and substituted lower alkyl; R4 is L3-X-L4-G, wherein,
L3 is optional, and when present is an optionally substituted or unsubstituted alkylene, optionally substituted or unsubstituted cycloalkylene, optionally substituted or unsubstituted alkenylene, optionally substituted or unsubstituted alkynylene;X is optional, and when present is 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(═NR1)NR10—, —OC(═NR11)—, or —C(═NR11)O—;L4 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, substituted or unsubstituted heterocycle;or L3, X and L4 taken together form a nitrogen containing heterocyclic ring;G is wherein,
R6, R7 and R8 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; 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; and R11 is selected from H, —S(═O)2R8, —S(═O)2NH2, —C(O)R8, —CN, —NO2, heteroaryl, or heteroalkyl; or a pharmaceutically acceptable salt thereof. |