TRYPTOLINE DERIVATIVES HAVING KINASE INHIBITORY ACTIVITY AND USES THEREOF

摘要

The present invention features tryptoline 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, pharmaceutically acceptable salt, or pharmaceutically acceptable prodrug thereof,
wherein each R1, R2, R3, and R4 is, independently, N or CR5, wherein each R5 is, independently, 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; A is H, optionally substituted C1-6 alkyl, optionally substituted C2-6 alkenyl, optionally substituted C2-6 alkynyl, optionally substituted C1-7 acyl, optionally substituted C1-12 heterocyclyl, carboxyl, —C(O)—NRA1RA2, or —NRA1—C(O)—RA2, wherein each RA1 and RA2 is, independently, H, optionally substituted C1-6 alkyl, optionally substituted C2-6 alkenyl, optionally substituted C2-6 alkynyl, or optionally substituted C1-6 alkoxy-C1-6 alkyl, or wherein the combination of RA1 and RA2 can together form optionally substituted C1-12 heterocyclyl; X is an optionally substituted C1-12 heterocyclyl or an optionally substituted C6-10 aryl; L is selected from the group consisting of optionally substituted C1-10 alkylene, optionally substituted C1-10 heteroalkylene, —O—CZ1Z2—, —CZ1Z2—O—, —S—CZ1Z2—, —CZ1Z2—S—, —NZN1—CZ1Z2—, —CZ1Z2—NZN1—, —O—, —S—, —NZN1—, —NZN1—C(O)—, and —C(O)—NZN1—, wherein each ZN1 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 Z1 and Z2 is, independently, H, optionally substituted C1-6 alkyl, optionally substituted C2-6 alkenyl, or optionally substituted C2-6 alkynyl, or wherein the combination of Z and Z2 can together form oxo or optionally substituted C1-7 spirocyclyl; each Z3a, Z3b, and Z4 is, independently, 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 C1-7 acyl, optionally substituted amino, halo, cyano, nitro, hydroxy, carboxyl, or an N-protecting group; or wherein the combination of Z3a and Z3b can together form oxo or optionally substituted C1-7 spirocyclyl; each Z5a and Z5b is, independently, 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 C1-7 acyl, optionally substituted amino, halo, cyano, nitro, hydroxy, or carboxyl; and Y is optionally substituted bicyclic C1-12 heterocyclyl.