INDOLINONE COMPOUNDS AND USES THEREOF

摘要

Indolinone derivative compounds that act as EWS-FLI1 transcription factor inhibitors are provided. Also provided are pharmaceutical compositions of the indolinone derivatives, methods of synthesizing the same, methods of treating using same, and assays for identifying the inhibitors of EWS-FLI1 oncoprotein.

主权项

1. A compound having a structure of Formula (I): or a stereoisomer, a pharmaceutically acceptable salt, or solvate thereof, wherein R1, R2, R3, and R4 are independently selected from the group consisting of H, Cl, —CN and —CF3; wherein A is selected from the group consisting of H and C1-6 alkyl; wherein D is selected from the group consisting of —OH and —O(C1-6 alkyl); wherein R5 and R6 are independently selected from the group consisting of H, F, and C1-6 alkyl, or wherein R5 and R6 taken together form a substituted or unsubstituted cycloalkyl ring; wherein R12 is independently selected from the group consisting of C3-8 cycloalkyl andwherein R7, R8, R9, R10 and R11 are independently selected from the group consisting of H, halogen, CN, CF3, C1-6 alkyl, aryl, heteroaryl, —O(aryl), —O(heteroaryl), —CO2H, —CO2(C1-6 alkyl), —NHSO2(C1-6 alkyl), —NHSO2 (aryl), —NHCONH(C1-6 alkyl), —NHCON(C1-6 alkyl)2, —N(C1-6 alkyl)CONH2, —N(C1-6 alkyl)CONH(C1-6 alkyl), —N(C1-6 alkyl)CON(C1-6 alkyl)2, —SO2(C1-6 alkyl), —SO2NH2, —SO2NH(C1-6 alkyl), —SO2N(C1-6 alkyl)2, C3-8 cycloalkyl, and C3-8 heterocycloalkyl.