Aryl ethers and uses thereof
AssigneePeloton Therapeutics, Inc.
InventorsDarryl David Dixon, Jonas Grina, John A. Josey, James P. Rizzi, Stephen T. Schlachter, Eli M. Wallace, Bin Wang, Paul Wehn, Rui Xu, Hanbiao Yang
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Abstract
The present disclosure relates to HIF-2α inhibitors and methods of making and using them for treating cancer. Certain compounds were potent in HIF-2α scintillation proximity assay, luciferase assay, and VEGF ELISA assay, and led to tumor size reduction and regression in 786-O xenograft bearing mice in vivo.
Claims18
A process for preparing 3-[(1S,2S,3R)-2,3-difluoro-1-hydroxy-7-methylsulfonyl-indan-4-yl]oxy-5-fluoro-benzonitrile, comprising:
- (i) fluorinating a compound of Formula A:
- to provide a compound of Formula B:
- and
- (ii) deprotecting the compound of Formula B to provide 3-[(1S,2S,3R)-2,3-difluoro-1-hydroxy-7-methylsulfonyl-indan-4-yl]oxy-5-fluoro-benzonitrile, represented by the formula:
- wherein P is a protecting group.
A process for preparing 3-fluoro-5-(((1S,2R)-2-fluoro-1-hydroxy-7-(methylsulfonyl)-2,3-dihydro-1H-inden-4-yl)oxy)benzonitrile, comprising:
- (i) fluorinating 3-fluoro-5-(7-methylsulfonyl-1-oxo-indan-4-yl)oxy-benzonitrile, represented by the formula:
- to provide 3-fluoro-5-((2-fluoro-7-(methylsulfonyl)-1-oxo-2,3-dihydro-1H-inden-4-yl)oxy)benzonitrile, represented by the formula:
- and
- (ii) reducing the 3-fluoro-5-((2-fluoro-7-(methylsulfonyl)-1-oxo-2,3-dihydro-1H-inden-4-yl)oxy)benzonitrile to provide the 3-fluoro-5-(((1S,2R)-2-fluoro-1-hydroxy-7-(methylsulfonyl)-2,3-dihydro-1H-inden-4-yl)oxy)benzonitrile, represented by the formula:
Dependencies are inferred from the claim text.