Kinase inhibitors and methods of use thereof

摘要

The present invention provides compounds of formula I, pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof. Compounds of the present invention are useful for inhibiting kinase (e.g., GSK3 (e.g., GSK3α or GSK3β) or CK1) activity. The present invention further provides methods of using the compounds described herein for treating kinase-mediated disorders, such as neurological diseases, psychiatric disorders, metabolic disorders, and cancer.;

主权项

1. A compound of formula I: or a pharmaceutically acceptable salt thereof, wherein
R1 and R2 are independently selected from the group consisting of optionally substituted aliphatic, optionally substituted aryl, and optionally substituted heteroaryl; or R1 and R2 are taken together with their intervening atoms to form an optionally substituted 3- to 7-membered saturated carbocyclic or heterocyclic ring, wherein the ring formed by R1 and R2 may be optionally fused to an aryl or heteroaryl ring;R3 is selected from the group consisting of hydrogen, halo, —CN, —NO2, optionally substituted aliphatic, optionally substituted phenyl, optionally substituted heterocyclyl, optionally substituted heteroaryl, —ORA, —N(RB)2, —SRA, —C(═O)RA, —C(═O)ORA, —C(═O)SRA, —C(═O)N(RB)2, —OC(═O)RA, —NRBC(═O)RA, —NRBC(═O)N(RB)2, —OC(═O)N(RB)2, —NRBC(═O)ORA, —SC(═O)RA, —C(═NRB)RA, —C(═NRB)N(RB)2, —NRBC(═NRB)RB, —C(═S)RA, —C(═S)N(RB)2, —NRBC(═S)RA, —S(═O)RA, —SO2RA, —NRBSO2RA, and —SO2N(RB)2;each RA is independently selected from the group consisting of hydrogen, optionally substituted aliphatic, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, and optionally substituted heteroaryl;each RB is independently selected from the group consisting of hydrogen, optionally substituted aliphatic, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, and optionally substituted heteroaryl, or two RB groups are taken together with their intervening atoms to form an optionally substituted heterocyclic ring;R4a and R4b are hydrogen;R5a and R5b are independently selected from the group consisting of hydrogen, halo, —CN, —ORA, —N(RB)2, and optionally substituted aliphatic, or R5a and R5b are taken together with their intervening atoms to form an optionally substituted 3- to 7-membered saturated carbocyclic or heterocyclic ring; andR6a and R6b are hydrogen.