Accessible Unlicensed Requires Authentication Published by De Gruyter February 4, 2015

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

Hiroyuki Nakamura, Lisa Tazaki, Daisuke Kanoh and Shinichi Sato


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.

Corresponding author: Hiroyuki Nakamura, Chemical Resources Laboratory, Tokyo Institute of Technology, 4259 Nagatsuta-cho, Midori-ku, Yokohama, 226-8503, Japan, e-mail: ; and Faculty of Science, Department of Chemistry, Gakushuin University, Mejiro, Tokyo 171-8588, Japan


We thank Dr. Hyun Seung Ban (Korea Research Institute of Bioscience and Biotechnology) for technical suggestions regarding hypoxia-induced HIF-1α protein and mRNA analyses. This work was supported by a Grant-in-Aid for Scientific Research on Innovative Areas “Chemical Biology of Natural Products” from The Ministry of Education, Culture, Sports, Science and Technology, Japan.


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Published Online: 2015-2-4
Published in Print: 2015-2-1

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