Benzhydrol-pyrazole derivatives having kinase inhibitory activity and uses thereof

摘要

The present invention features benzhydrol-pyrazole derivatives and related compounds having kinase inhibitory activity. The compounds of the invention, alone or in combination with other pharmaceutically active agents, can be used for treating or preventing various medical conditions, such as cancers, inflammatory disorders, or autoimmune disorders.

主权项

1. A compound having the formula:or a stereoisomer or pharmaceutically acceptable salt thereof,
wherein n is an integer from 0 to 4, and each R1 is, independently, optionally substituted C1-6 alkyl, optionally substituted C2-6 alkenyl, optionally substituted C2-6 alkynyl, optionally substituted halo-C1-6 alkyl, optionally substituted C1-6 alkoxy, optionally substituted C2-6 alkenyloxy, optionally substituted C2-6 alkynyloxy, optionally substituted halo-C1-6 alkoxy, optionally substituted C1-6 alkoxy-C1-6 alkyl, optionally substituted C1-7 acyl, optionally substituted C1-7 acylamino, optionally substituted C1-7 acyloxy, optionally substituted C6-10 aryl, optionally substituted C1-6 alk-C6-10 aryl, optionally substituted amino, halo, cyano, nitro, hydroxy, or carboxyl; Ar is optionally substituted C6-10 aryl or optionally substituted C1-12 heteroaryl; R2 is independently, H, optionally substituted C2-6 alkenyl, optionally substituted C2-6 alkynyl, optionally substituted halo-C1-6 alkyl, optionally substituted C1-6 alkoxy, optionally substituted C2-6 alkenyloxy, optionally substituted C2-6 alkynyloxy, optionally substituted halo-C1-6 alkoxy, optionally substituted C1-7 acyl, optionally substituted amino, halo, cyano, nitro, hydroxy, carboxyl, or an N-protecting group; Y is —CY1Y2—NYN1-, wherein each YN1 is, independently, H, optionally substituted C1-6 alkyl, optionally substituted C2-6 alkenyl, optionally substituted C2-6 alkynyl, or an N-protecting group; and wherein each Y1 and Y2 is, independently, H, optionally substituted C1-6 alkyl, optionally substituted C2-6 alkenyl, or optionally substituted C2-6 alkynyl; or wherein the combination of Y1 and Y2 can together form oxo or optionally substituted C1-7 spirocyclyl; Z is H, optionally substituted C1-6 alkyl, optionally substituted C2-6 alkenyl, optionally substituted C2-6 alkynyl, optionally substituted halo-C1-6 alkyl, optionally substituted C1-6 alkoxy, optionally substituted C2-6 alkenyloxy, optionally substituted C2-6 alkynyloxy, optionally substituted halo-C1-6 alkoxy, optionally substituted C1-6 alkoxy-C1-6 alkyl, optionally substituted C1-7 acyl, optionally substituted C1-7 acylamino, optionally substituted C1-7 acyloxy, optionally substituted C6-10 aryl, optionally substituted C1-6 alk-C6-10 aryl, optionally substituted amino, halo, cyano, nitro, hydroxy, or carboxyl; L is optionally substituted C1-10 alkylene, optionally substituted C1-10 heteroalkylene, —NRL3—C(O)—, —C(O)—NRL3—, —NRL3—CRL1RL2—, —CRL1RL2NRL3—, or a bond, wherein each RL1 and RL2 is, independently, H, optionally substituted C1-6 alkyl, optionally substituted C2-6 alkenyl, optionally substituted C2-6 alkynyl; or wherein the combination of RL1 and RL2 can together form oxo or optionally substituted C1-7 spirocyclyl; and wherein each RL3 is, independently, H, optionally substituted C1-6 alkyl, optionally substituted C2-6 alkenyl, optionally substituted C2-6 alkynyl, or an N-protecting group; and X is optionally substituted C1-6 alkyl, optionally substituted C3-8 cycloalkyl, optionally substituted C6-10 aryl, or optionally substituted C1-12 heterocyclyl.