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)-1 alpha inhibitors. Among the compounds synthesized, carboranylphenoxy-acetanilide 16 (GN26361) was found to be a potent inhibitor against HIF-1 alpha accumulation under hypoxic conditions and inhibited the hypoxia-induced HIF-1 transcriptional activity in HeLa cells (IC50 = 0.74 mu M). Compound 16 suppressed hypoxia-induced HIF-1 alpha accumulation and vascular endothelial growth factor mRNA expression in a concentration-dependent manner without affecting the expression of HIF-1 alpha mRNA. (C) 2009 Elsevier Ltd. All rights reserved.