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Development of p-carborane-based nonsteroidal progesterone receptor antagonists
Shinya Fujii1, Eiichi Nakano2, Naoki Yanagida2
1Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University, 2-3-10 Kanda-Surugadai, Chiyoda-ku, Tokyo 101-0062, Japan; Institute of Molecular and Cellular Biosciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan.
Abstract:
Progesterone receptor (PR) regulates various physiological processes, including the female reproductive system, and development of nonsteroidal PR antagonists is considered desirable for clinical application, as they are expected to have reduced side effects. We have synthesized a series of nonsteroidal PR antagonists using a 4-cyanophenyl-p-carborane core structure. Among them, compound 14d exhibited potent PR-antagonistic activity (IC50: 27 nM). It showed high binding affinity for PR, but did not bind to androgen receptor or estrogen receptor. This PR-selective antagonist may be a promising lead compound for clinically applicable progesterone receptor modulators.
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