Novel selective anti-androgens with a diphenylpentane skeleton

Keisuke Maruyama, Tomomi Noguchi-Yachide, Kazuyuki Sugita, Yuichi Hashimoto, Minoru Ishikawa

Research output: Contribution to journalArticlepeer-review

21 Citations (Scopus)


We have proposed a multi-template approach for drug development, focusing on similar fold structures of proteins, and have effectively generated lead compounds for several drug targets. Modification of these polypharmacological lead compounds is then needed to generate target-selective compounds. In the work presented here, we aimed at separation of the anti-androgen activity and vitamin D activity of previously identified diphenylpentane lead compounds. Based on the determined X-ray crystal structures of androgen receptor and vitamin D receptor, bulky substituents were introduced at the t-butyl group in the lead compounds 2 and 3. As a result of this structural development, we obtained 16c, which exhibits more potent anti-androgen activity (IC 50: 0.13 μM) than clinically used anti-androgen bicalutamide (IC50: 0.67 μM) with 30-fold selectivity over vitamin D activity. This result indicates that lead compounds obtained via the multi-template approach can indeed be structurally modified to generate target-selective compounds.

Original languageEnglish
Pages (from-to)6661-6666
Number of pages6
JournalBioorganic and Medicinal Chemistry Letters
Issue number22
Publication statusPublished - 2010 Nov 15


  • Anti-androgen
  • Diphenylpentane
  • Steroid surrogate


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