COMPOSITIONS OF KINASE INHIBITORS AND THEIR USE FOR TREATMENT OF CANCER AND OTHER DISEASES RELATED TO KINASES

摘要

The present invention relates to novel thiazole-substituted indolin-2-ones as inhibitors of CSCPK and related kinases; to methods of inhibiting cancer stem cells by using a kinase inhibitor; to pharmaceutical compositions containing such compounds; and to methods of using such compounds in the treatment of a protein kinase related disorder in a mammal; and to processes of making such compounds and intermediates thereof.

主权项

1. A compound of formula IV, or an enantiomer, diastereomer, tautomer, or pharmaceutically acceptable salt or solvate thereof, wherein the symbols have the following meanings and are, for each occurrence, independently selected: R1 is hydrogen, alkyl or substituted alkyl, alkenyl or substituted alkenyl, alkynyl or substituted alkynyl, cycloalkyl or substituted cycloalkyl, cycloalkenyl or substituted cycloalkenyl, heterocycle or substituted heterocycle, aryl or substituted aryl, ORa, SRa, S(═O)2Re, S(═O)2ORe, C(═O)ORd, C(═O)Ra, or C(═O)NRbRc; R3 and R10 are each independently hydrogen, alkyl or substituted alkyl, cycloalkyl or substituted cycloalkyl, heterocycle or substituted heterocycle, aryl or substituted aryl; R4, R7, and R8 are each independently hydrogen, halogen, cyano, nitro, CF3, OCF3, alkyl or substituted alkyl, alkenyl or substituted alkenyl, alkynyl or substituted alkynyl, cycloalkyl or substituted cycloalkyl, cycloalkenyl or substituted cycloalkenyl, heterocycle or substituted heterocycle, aryl or substituted aryl, ORa, SRa, S(═O)Re, S(═O)2Re, P(═O)2Re, S(═O)2ORe, P(═O)2ORe, NRbRc, NRbS(═O)2Re, NRbP(═O)2Re, S(═O)2NRbRc, P(═O)2NRbRc, C(═O)ORe, C(═O)Ra, C(═O)NRbRc, OC(═O)Ra, OC(═O)NRbRc, NRbC(═O)ORe, NRdC(═O)NRbRc, NRdS(═O)2NRbRc, NRdP(═O)2NRbRc, NRbC(═O)Ra, or NRbP(═O)2Re; R5 is alkyl or substituted alkyl, heterocycle or substituted heterocycle, aryl or substituted aryl; R6 and R9 are each independently hydrogen, halogen, cyano, nitro, CF3, OCF3, alkyl or substituted alkyl, heterocycle or substituted heterocycle, aryl or substituted aryl, or ORa; R14 and R15 are independently hydrogen, alkyl or substituted alkyl, cycloalkyl or substituted cycloalkyl, heterocycle or substituted heterocycle, or aryl or substituted aryl, or said R14 and R15 together with the N to which they are bonded optionally form a heterocycle or substituted heterocycle; Ra is hydrogen, alkyl or substituted alkyl, alkenyl or substituted alkenyl, alkynyl or substituted alkynyl, cycloalkyl or substituted cycloalkyl, cycloalkenyl or substituted cycloalkenyl, heterocycle or substituted heterocycle, or aryl or substituted aryl; Rb, Rc and Rd are independently hydrogen, alkyl or substituted alkyl, cycloalkyl or substituted cycloalkyl, heterocycle or substituted heterocycle, or aryl or substituted aryl, or said Rb and Rc together with the N to which they are bonded optionally form a heterocycle or substituted heterocycle; and Re is alkyl or substituted alkyl, alkenyl or substituted alkenyl, alkynyl or substituted alkynyl, cycloalkyl or substituted cycloalkyl, cycloalkenyl or substituted cycloalkenyl, heterocycle or substituted heterocycle, or aryl or substituted aryl.