Novel Nonsteroidal Progesterone Receptor (PR) Antagonists with a Phenanthridinone Skeleton

Yuko Nishiyama, Shuichi Mori, Makoto Makishima, Shinya Fujii, Hiroyuki Kagechika, Yuichi Hashimoto, Minoru Ishikawa

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

The progesterone receptor (PR) plays an important role in various physiological systems, including female reproduction and the central nervous system, and PR antagonists are thought to be effective not only as contraceptive agents and abortifacients but also in the treatment of various diseases, including hormone-dependent cancers and endometriosis. Here, we identified phenanthridin-6(5H)-one derivatives as a new class of PR antagonists and investigated their structure-activity relationships. Among the synthesized compounds, 37, 40, and 46 exhibited very potent PR antagonistic activity with high selectivity for PR over other nuclear receptors. These compounds are structurally distinct from other nonsteroidal PR antagonists, including cyanoaryl derivatives, and should be useful for further studies of the clinical utility of PR antagonists.

Original languageEnglish
Pages (from-to)641-645
Number of pages5
JournalACS Medicinal Chemistry Letters
Volume9
Issue number7
DOIs
Publication statusPublished - 2018 Jul 12
Externally publishedYes

Keywords

  • Progesterone receptor
  • antagonist
  • nonsteroid
  • phenanthridinone

ASJC Scopus subject areas

  • Biochemistry
  • Drug Discovery
  • Organic Chemistry

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