Bibenzyl- and stilbene-core compounds with non-polar linker atom substituents as selective ligands for estrogen receptor beta

Michael Waibel, Meri De Angelis, Fabio Stossi, Karen J. Kieser, Kathryn E. Carlson, Benita S. Katzenellenbogen, John A. Katzenellenbogen

Research output: Contribution to journalArticle

Abstract

A series of structurally simple bibenzyl-diol and stilbene-diol core molecules, structural analogs of the well-known hexestrol and diethylstilbestrol non-steroidal estrogens, were prepared and evaluated as estrogen receptor (ER) subtype-selective ligands. Analysis of their ERα and ERβ binding showed that certain substitution patterns engendered binding affinities that were >100-fold selective for ERβ. When further investigated in cell-based gene transcription assays, some molecules showed similarly high relative transcriptional potency selectivity in favor of ERβ. Interestingly, the most ERβ-selective molecules were those bearing non-polar substituents on one of the internal carbon atoms. These compounds should be useful probes for determining the physiological roles of ERβ, and they might lead to the development of more selective and thus safer pharmaceuticals.

Original languageEnglish (US)
Pages (from-to)3412-3424
Number of pages13
JournalEuropean Journal of Medicinal Chemistry
Volume44
Issue number9
DOIs
StatePublished - Sep 1 2009

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Keywords

  • Estrogen receptor
  • Estrogen receptor beta
  • Hexestrol
  • Selective ligand
  • Stilbestrol

ASJC Scopus subject areas

  • Pharmacology
  • Drug Discovery
  • Organic Chemistry

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