1-[4-(N-Benzylamino)phenyl]-3-phenylurea derivatives as a new class of hypoxia-inducible factor-1α inhibitors

A series of 1-[4-(N-benzylamino)phenyl]-3-phenylurea derivatives 2a–r were synthesized as HIF-1α inhibitors. Among the compounds synthesized, compound 2k was found to be a potent inhibitor against HIF-1α accumulation under hypoxic condition and inhibited the hypoxia-induced HIF-1 transcriptional activity in HEK293 cells (IC50 = 7.2 μM). Furthermore, compound 2k suppressed the hypoxia-induced secretion of VEGF in HeLa cells (IC50 = 15 μM).

Graphical abstractCompound 2k was found to be a potent inhibitor against HIF-1α accumulation under hypoxic condition without affecting the mRNA expression level of HIF-1α.Figure optionsDownload full-size imageDownload as PowerPoint slide