title: Boron-containing phenoxyacetanilide derivatives as hypoxia-inducible factor (HIF)-1alpha inhibitors.
abstract: A series of boron-containing phenoxyacetanilide derivatives 8a-f, 9a-f, 15, and 16 were synthesized as hypoxia-inducible factor (HIF)-1alpha inhibitors. Among the compounds synthesized, carboranylphenoxyacetanilide 16 (GN26361) was found to be a potent inhibitor against HIF-1alpha accumulation under hypoxic conditions and inhibited the hypoxia-induced HIF-1 transcriptional activity in HeLa cells (IC50=0.74 microM). Compound 16 suppressed hypoxia-induced HIF-1alpha accumulation and vascular endothelial growth factor mRNA expression in a concentration-dependent manner without affecting the expression of HIF-1alpha mRNA.
authors.affiliation: Department of Chemistry, Faculty of Science, Gakushuin University, Mejiro, Tokyo 171-8588, Japan.
authors.forename: Kazuki
authors.initials: K
authors.lastname: Shimizu
authors.forename: Minako
authors.initials: M
authors.lastname: Maruyama
authors.forename: Yuka
authors.initials: Y
authors.lastname: Yasui
authors.forename: Hidemitsu
authors.initials: H
authors.lastname: Minegishi
authors.forename: Hyun Seung
authors.initials: HS
authors.lastname: Ban
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Nakamura
mesh_terms: D000083:Acetanilides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001895:Boron / Q000737:chemistry*; D001896:Boron Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001897:Boronic Acids; D005786:Gene Expression Regulation / Q000187:drug effects; D006367:HeLa Cells; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000037:antagonists & inhibitors* / Q000235:genetics; D020128:Inhibitory Concentration 50; D010636:Phenols / Q000737:chemistry*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D014158:Transcription, Genetic
chemical_list: D000083:Acetanilides; D001896:Boron Compounds; D001897:Boronic Acids; C549649:GN 26361; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D010636:Phenols; D012333:RNA, Messenger; D001895:Boron