Boron-containing phenoxyacetanilide derivatives as hypoxia-inducible factor (HIF)-1α inhibitors

A series of boron-containing phenoxyacetanilide derivatives 8a–f, 9a–f, 15, and 16 were synthesized as hypoxia-inducible factor (HIF)-1α inhibitors. Among the compounds synthesized, carboranylphenoxyacetanilide 16 (GN26361) was found to be a potent inhibitor against HIF-1α accumulation under hypoxic conditions and inhibited the hypoxia-induced HIF-1 transcriptional activity in HeLa cells (IC50 = 0.74 μM). Compound 16 suppressed hypoxia-induced HIF-1α accumulation and vascular endothelial growth factor mRNA expression in a concentration-dependent manner without affecting the expression of HIF-1α mRNA.

Compound 16 (GN25361) 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 as PowerPoint slide