Synthesis and structure-activity relationship of (E)-phenoxyacrylic amide derivatives as Hypoxia-Inducible Factor (HIF) 1α inhibitors

Ravi Naik, Misun Won, Bo Kyung Kim, Yan Xia, Hyun Kyung Choi, Guanghai Jin, Youngjin Jung, Hwan Mook Kim, Kyeong Lee

Research output: Contribution to journalArticlepeer-review

26 Scopus citations

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.

Original languageEnglish
Pages (from-to)10564-10571
Number of pages8
JournalJournal of Medicinal Chemistry
Volume55
Issue number23
DOIs
StatePublished - 13 Dec 2012

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