title: Synthesis and structure-activity relationship of (E)-phenoxyacrylic amide derivatives as hypoxia-inducible factor (HIF) 1α inhibitors.
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.
authors.affiliation: College of Pharmacy, Dongguk University-Seoul, Seoul 100-715, Republic of Korea.
authors.forename: Ravi
authors.initials: R
authors.lastname: Naik
authors.forename: Misun
authors.initials: M
authors.lastname: Won
authors.forename: Bo-Kyung
authors.initials: BK
authors.lastname: Kim
authors.forename: Yan
authors.initials: Y
authors.lastname: Xia
authors.forename: Hyun Kyung
authors.initials: HK
authors.lastname: Choi
authors.forename: Guanghai
authors.initials: G
authors.lastname: Jin
authors.forename: Youngjin
authors.initials: Y
authors.lastname: Jung
authors.forename: Hwan Mook
authors.initials: HM
authors.lastname: Kim
authors.forename: Kyeong
authors.initials: K
authors.lastname: Lee
mesh_terms: D000178:Acrylamides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000037:antagonists & inhibitors*; D009682:Magnetic Resonance Spectroscopy; D021241:Spectrometry, Mass, Electrospray Ionization; D013329:Structure-Activity Relationship
chemical_list: D000178:Acrylamides; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit