Synthesis and Structure鈥揂ctivity Relationship of (E)-Phenoxyacrylic Amide Derivatives as Hypoxia-Inducible Factor (HIF) 1伪 Inhibitors

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• 作者：Ravi Naik ; Misun Won ; Bo-Kyung Kim ; Yan Xia ; Hyun Kyung Choi ; Guanghai Jin ; Youngjin Jung ; Hwan Mook Kim ; Kyeong Lee
• 刊名：Journal of Medicinal Chemistry
• 出版年：2012
• 出版时间：December 13, 2012
• 年：2012
• 卷：55
• 期：23
• 页码：10564-10571
• 全文大小：463K
• 年卷期：v.55,no.23(December 13, 2012)
• ISSN：1520-4804

文摘

A series of (E)-phenoxyacrylic amide derivatives were synthesized and evaluated as hypoxia inducible factor (HIF) 1伪 inhibitors. The present structure鈥揳ctivity relationship study on this series identified the morpholinoethyl containing ester 4p as a potent inhibitor of HIF-1伪 under hypoxic conditions (IC₅₀ = 0.12 渭M in a cell-based HRE reporter assay) in HCT116 cells. The representative compound 4p suppressed hypoxia-induced HIF-1伪 accumulation and targeted gene expression in a dose-dependent manner. The effect of HIF-1伪 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.