| 摘要 |
Disclosed herein are compounds that form covalent bonds with Bruton's tyrosine kinase (Btk). Also described are irreversible inhibitors of Btk. Methods for the preparation of the compounds are disclosed. 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 composition comprising rituximab and a compound of Formula (D) having the structure:wherein:
La is CH2, O, NH or S; Ar is a substituted or unsubstituted aryl, or a substituted or unsubstituted heteroaryl; Y is an optionally substituted group selected from the group consisting of alkyl, heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl; Z is C(═O), OC(═O), NHC(═O), C(═S), S(═O)x, OS(═O)x, or NHS(═O)x, where x is 1 or 2; R7 and R8 are independently selected from the group consisting of H, unsubstituted C1-C4 alkyl, substituted C1-C4alkyl, unsubstituted C1-C4heteroalkyl, substituted C1-C4heteroalkyl, unsubstituted C3-C6cycloalkyl, substituted C3-C6cycloalkyl, unsubstituted C2-C6heterocycloalkyl, and substituted C2-C6heterocycloalkyl; or R7 and R8 taken together form a bond; R6 is selected from the group consisting of H, substituted or unsubstituted C1-C4alkyl, substituted or unsubstituted C1-C4heteroalkyl, C1-C6alkoxyalkyl, C1-C8alkylaminoalkyl, substituted or unsubstituted C3-C6cycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted C2-C8heterocycloalkyl, substituted or unsubstituted heteroaryl, C1-C4alkyl(aryl), C1-C4alkyl(heteroaryl), C1-C4alkyl(C3-C8cycloalkyl), and C1-C4alkyl(C2-C8heterocycloalkyl); or a pharmaceutically active metabolite, or a pharmaceutically acceptable solvate, or a pharmaceutically acceptable salt, or a pharmaceutically acceptable prodrug thereof, or a stereoisomer thereof. |
