Inhibitors of Bruton's tyrosine kinase

摘要

Disclosed herein are reversible and irreversible inhibitors of Bruton's tyrosine kinase (Btk). Also disclosed are pharmaceutical compositions that include the compounds. Methods of using the Btk inhibitors are described, 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 (IA) having the structure: wherein:
ring A is substituted or unsubstituted C3-C6cycloalkyl, substituted or unsubstituted C2-C7heterocycloalkyl, substituted or unsubstituted C6-C12aryl, or substituted or unsubstituted C1-C12heteroaryl;Y is optionally present and when present is —CH2O—, —OCH2—, —OCH2CH2O—, —O—, —N(R3)—, —C(O)—, —N(R3)C(O)—, —C(O)N(R3)—, —N(R3)C(O)N(R3)—, —S(O)—, —S(O)2—, —N(R3)S(O)2—, —S(O)2N(R3)—, —C(═NH)—, —C(═NH)N(R3)—, —C(═NH)N(R3)—, or substituted or unsubstituted C1-C4alkylene;Z is optionally present and when present is substituted or unsubstituted C1-C3alkyl, substituted or unsubstituted C3-C6cycloalkyl, substituted or unsubstituted C2-C7heterocycloalkyl, substituted or unsubstituted C6-C12aryl, or substituted or unsubstituted C1-C12heteroaryl;R1 is —C(O)R4, —C(O)C(O)R4, —C(O)N(R3)(R4), or —S(O)2R4;each R2 is independently H, substituted or unsubstituted C1-C4alkyl, —CN, or halogen;each R3 is independently is H, or substituted or unsubstituted C1-C4alkyl;each R4 is independently H, substituted or unsubstituted C1-C6alkyl, substituted or unsubstituted C3-C6cycloalkyl, substituted or unsubstituted C2-C7heterocycloalkyl, substituted or unsubstituted C6-C12aryl, or substituted or unsubstituted C1-C12heteroaryl;R5 is H, substituted or unsubstituted C1-C4alkyl, substituted or unsubstituted C3-C6cycloalkyl, substituted or unsubstituted C2-C7heterocycloalkyl, substituted or unsubstituted C6-C12aryl, or substituted or unsubstituted C1-C12heteroaryl; or R1 and R5 together with the nitrogen atom to which they are attached are combined to form a substituted or unsubstituted C2-C9heterocycloalkyl ring;each R6 is independently halogen, —CN, —OH, —NH2, substituted or unsubstituted C1-C4alkoxy, substituted or unsubstituted C1-C4alkyl, substituted or unsubstituted C3-C6cycloalkyl, substituted or unsubstituted C2-C6heterocycloalkyl, or —N(R3)2; or R1 and R6 are combined to form a substituted or unsubstituted C2-C9heterocycloalkyl ring;each R7 is independently halogen, —CN, —OH, —NH2, substituted or unsubstituted C1-C4alkoxy, substituted or unsubstituted C1-C4alkyl, substituted or unsubstituted C3-C6cycloalkyl, substituted or unsubstituted C2-C6heterocycloalkyl, or —N(R3)2;n is 0-3;p is 0-3; andq is 0-3; or a pharmaceutically acceptable solvate, or pharmaceutically acceptable salt thereof; provided that when n is 0; then each of p and q is independently 0, 1, or 2.