1-[4-(N-Benzylamino)phenyl]-3-phenylurea derivatives as a new class of hypoxia-inducible factor-1alpha inhibitors.
A series of 1-[4-(N-benzylamino)phenyl]-3-phenylurea derivatives 2a-r were synthesized as HIF-1alpha inhibitors. Among the compounds synthesized, compound 2k was found to be a potent inhibitor against HIF-1alpha accumulation under hypoxic condition and inhibited the hypoxia-induced HIF-1 transcriptional activity in HEK293 cells (IC(50)=7.2 microM). Furthermore, compound 2k suppressed the hypoxia-induced secretion of VEGF in HeLa cells (IC(50)=15 microM).
Department of Chemistry, Faculty of Science, Gakushuin University, Mejiro, Tokyo 171-8588, Japan.
Masaharu
M
Uno
Hyun Seung
HS
Ban
Hiroyuki
H
Nakamura
D002460:Cell Line; D006367:HeLa Cells; D006801:Humans; D000860:Hypoxia / Q000188:drug therapy; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000037:antagonists & inhibitors* / Q000235:genetics; D020128:Inhibitory Concentration 50; D010671:Phenylurea Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014158:Transcription, Genetic / Q000187:drug effects; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors / Q000378:metabolism
D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D010671:Phenylurea Compounds; D042461:Vascular Endothelial Growth Factor A