Diaryl-substituted carboranes as inhibitors of hypoxia inducible factor-1 transcriptional activity

Diaryl-substituted carboranes, as a new class of HIF-1α inhibitors, were synthesized from the corresponding diaryl-substituted alkynes by decaborane coupling. The microwave-irradiated conditions with a combination of N,N-dimethylaniline and chlorobenzene were effective to obtain the diaryl-substituted carboranes in good to high yields. Among the compounds synthesized, compounds 1a and 1d showed significant inhibition of HIF-1 mediated transcriptional activity under hypoxia. Both compounds similarly suppressed hypoxia-induced HIF-1α accumulation in a concentration-dependent manner without affecting HIF-1α mRNA expression.