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

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Title
Synthesis and structure-activity relationship of (E)-phenoxyacrylic amide derivatives as Hypoxia-Inducible Factor (HIF) 1α inhibitors
Author(s)
Naik; Mi Sun WonBo Kyung Kim; Y Xia; H K Choi; G Jin; Y Jung; H M Kim; K Lee
Bibliographic Citation
Journal of Medicinal Chemistry, vol. 55, no. 23, pp. 10564-10571
Publication Year
2012
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.
ISSN
0022-2623
Publisher
Amer Chem Soc
DOI
http://dx.doi.org/10.1021/jm301419d
Type
Article
Appears in Collections:
Division of Biomedical Research > Personalized Genomic Medicine Research Center > 1. Journal Articles
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