| 摘要 |
Provided herein are dipeptide and tripeptide epoxy ketone protease inhibitors, methods of their preparation, related pharmaceutical compositions, and methods of using the same. For example, provided herein are compounds of Formula (X): and pharmaceutically acceptable salts and compositions including the same. The compounds and compositions provided herein may be used, for example, in the treatment of proliferative diseases including cancer and autoimmune diseases.; |
| 主权项 |
1. A compound of Formula (X), or a pharmaceutical salt thereof: wherein: p is 0 or 1; q is 0, 1, or 2; J is selected from the group consisting of C1-6alkyleneR5, C2-6alkenyleneR5, OC1-6alkyleneR5, CF3, C0-6alkyleneN(R6)2, aryl, heteroaryl, polyetherCH3, and C3-6cycloalkenyl, wherein J is optionally substituted with one or more substituents selected from the group consisting of C1-6alkyl, halo, CF3, OR6, SR6, N(R6)2, and 3-7 membered heterocycloalkyl; R1 is selected from the group consisting of H, C1-2alkyleneR7, C3-6cycloalkyl, and 3-6 membered heterocycloalkyl, wherein R1 is optionally substituted with one or more substituents selected from the group consisting of halo, OR6, SR6, and N(R6)2; R2 is C1-2alkylene-G; wherein G is selected from the group consisting of C3-7cycloalkenyl, aryl, and heteroaryl, with the proviso that when R2 is CH2phenyl, the phenyl is substituted with one or more substituents selected from the group consisting of OR6, halo, C1-3alkyl, and SO2R6; R3 is selected from the group consisting of C3-7cycloalkyl, C3-7cycloalkenyl, a 3-7 membered heterocycloalkyl, a 3-7 membered heterocycloalkenyl and aryl, wherein R3 is optionally substituted with one or more substituents selected from the group consisting OR6 and C1-6alkyl; R4 is H or C1-3alkyl; R5 is selected from the group consisting of H, CF3, OR6, C1-6alkoxyl, and aryl; each R6 is independently H or C1-6alkyl; and, R7 is selected from the group consisting of H, OR6, COOR6, CN, and 3-6 membered heterocycloalkyl. |
