INHIBITORS OF BRUTON'S TYROSINE KINASE

摘要

Disclosed herein are compounds that form covalent bonds with Bruton's tyrosine kinase (Btk). Also described are irreversible inhibitors of Btk. In addition, reversible inhibitors of Btk are also described. Also disclosed are pharmaceutical compositions that include the compounds. Methods of using the Btk inhibitors are disclosed, alone or in combination with other therapeutic agents, for the treatment of autoimmune diseases or conditions, heteroimmune diseases or conditions, cancer, including lymphoma, and inflammatory diseases or conditions.

主权项

1. A compound of Formula (IV) having the structure:wherein:
ring A is C6-C12aryl or C3-C12heteroaryl; X is substituted or unsubstituted C2-C4alkyl, substituted or unsubstituted C3-C8cycloalkyl, substituted or unsubstituted C6-C12aryl or substituted or unsubstituted C3-C12heteroaryl; L1 is —N(R2)C(O)— or —C(O)N(R2)—; R1 is C6-C12aryl or C3-C12heteroaryl, which may optionally be substituted with at least one R3; R2 is H or C1-C4alkyl; R3 is halogen, —CF3, —CN, —NO2, —OR6, —N(R11)(R12), substituted or unsubstituted C1-C6alkyl, substituted or unsubstituted C3-C6cycloalkyl, or substituted or unsubstituted C1-C6heteroalkyl; R6 is H or L-J-W; R7 and R8 are independently H or L-J-W; or R7 and R8 taken together form a bond; L and J are each independently a bond, substituted or unsubstituted C1-C6 alkylene, substituted or unsubstituted C3-C6 cycloalkylene, substituted or unsubstituted C1-C6 heteroalkylene, substituted or unsubstituted C2-C7 heterocycloalkylene, substituted or unsubstituted C6-C12 arylene, substituted or unsubstituted C3-C12 heteroarylene, —CO—, —O—, or —S—; W is H, or NR25R26; R9 is H, or substituted or unsubstituted C1-C6alkyl; R10 is halogen, substituted or unsubstituted C1-C6alkyl, or substituted or unsubstituted C1-C6alkoxy; R11 is H, substituted or unsubstituted C1-C6alkyl, or substituted or unsubstituted C1-C6heteroalkyl; R12 is H, substituted or unsubstituted C1-C6alkyl, or substituted or unsubstituted C1-C6heteroalkyl; R25 and R26 are each independently H, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C3-C6 cycloalkyl, substituted or unsubstituted C1-C6 heteroalkyl, substituted or unsubstituted C2-C7 heterocycloalkyl, substituted or unsubstituted C6-C12 aryl, or substituted or unsubstituted C3-C12 heteroaryl; or R25 and R26 together with the nitrogen atom to which they are attached form a C2-C9heterocycloalkyl; p is 0, 1, or 2;or a pharmaceutically acceptable salt, or pharmaceutically acceptable solvate thereof.