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J Med Chem. 2012 Dec 13;55(23):10564-71. doi: 10.1021/jm301419d. Epub 2012 Nov 15.

Synthesis and structure-activity relationship of (E)-phenoxyacrylic amide derivatives as hypoxia-inducible factor (HIF) 1α inhibitors.

Author information

1
College of Pharmacy, Dongguk University-Seoul, Seoul 100-715, Republic of Korea.

Abstract

A series of (E)-phenoxyacrylic amide derivatives were synthesized and evaluated as hypoxia inducible factor (HIF) 1α inhibitors. The present structure-activity relationship study on this series identified the morpholinoethyl containing ester 4p as a potent inhibitor of HIF-1α under hypoxic conditions (IC50=0.12 μM in a cell-based HRE reporter assay) in HCT116 cells. The representative compound 4p suppressed hypoxia-induced HIF-1α accumulation and targeted gene expression in a dose-dependent manner. The effect of HIF-1α inhibition by 4p was further demonstrated by its inhibitory activity on in vitro tube formation and migration of cells, which may be valuable for development of novel therapeutics for cancer and tumor angiogenesis.

PMID:
23153200
DOI:
10.1021/jm301419d
[Indexed for MEDLINE]

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