Indolinone compounds and uses thereof
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.
1. A compound having a structure of Formula (Ia):
or a stereoisomer, a pharmaceutically acceptable salt, or solvate thereof, wherein R 1 , R 2 , R 3 , and R 4 are independently selected from the group consisting of H and Cl; wherein R 7 , R 8 , R 10 and R 11 are independently selected from the group consisting of H and halogen; and wherein R 9 is C 3-8 cycloalkyl.
2. The compound of claim 1 , wherein R 1 and R 4 are Cl, and R 2 and R 3 are H.
3. The compound of claim 1 , selected from the group consisting of
or a stereoisomer, a pharmaceutically acceptable salt, ester, or solvate thereof.
4. A compound having a structure:
or a stereoisomer, a pharmaceutically acceptable salt, ester, or solvate thereof.
5. A pharmaceutical composition comprising the compound of claim 1 , and a pharmaceutically acceptable carrier.
6. The compound of claim 4 , having a structure:
7. The compound of claim 4 , having a structure:
8. A pharmaceutical composition comprising the compound of claim 4 , and a pharmaceutically acceptable carrier.
9. A compound having a structure of Formula (Ia):
wherein R 1 , R 2 , R 3 , and R 4 are independently selected from the group consisting of H and Cl; wherein R 7 , R 8 , R 10 and R 11 are independently selected from the group consisting of H and halogen; and wherein R 9 is C 3-8 cycloalkyl.
10. The compound of claim 9 , wherein R 1 and R 4 are Cl, and R 2 and R 3 are H.
11. The compound of claim 9 , selected from the group consisting of:
12. A pharmaceutical composition comprising the compound of claim 9 , and a pharmaceutically acceptable carrier.
13. A compound having a structure:
14. A pharmaceutical composition comprising the compound of claim 13 , and a pharmaceutically acceptable carrier.