A new Suzuki synthesis of triphenylethylenes that inhibit aromatase and bind to estrogen receptors α and β

Li Ming Zhao, Hai Shan Jin, Jinzhong Liu, Todd C. Skaar, Joseph Ipe, Wei Lv, David A. Flockhart, Mark Cushman

Research output: Contribution to journalArticle

7 Scopus citations


The design and synthesis of dual aromatase inhibitors/selective estrogen receptor modulators (AI/SERMs) is an attractive strategy for the discovery of new breast cancer therapeutic agents. Previous efforts led to the preparation of norendoxifen (4) derivatives with dual aromatase inhibitory activity and estrogen receptor binding activity. In the present study, some of the structural features of the potent AI letrozole were incorporated into the lead compound (norendoxifen) to afford a series of new dual AI/SERM agents based on a symmetrical diphenylmethylene substructure that eliminates the problem of E,Z isomerization encountered with norendoxifen-based AI/SERMs. Compound 12d had good aromatase inhibitory activity (IC50 = 62.2 nM) while also exhibiting good binding activity to both ER-α (EC50 = 72.1 nM) and ER-β (EC50 = 70.8 nM). In addition, a new synthesis was devised for the preparation of norendoxifen and its analogues through a bis-Suzuki coupling strategy.

Original languageEnglish (US)
Pages (from-to)5400-5409
Number of pages10
JournalBioorganic and Medicinal Chemistry
Issue number21
StatePublished - Jan 1 2016



  • (E,Z)-Norendoxifen synthesis
  • Antiestrogenic activity
  • Aromatase inhibitor
  • Breast cancer
  • Estrogen receptor

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

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