Phenethyl pyridines with non-polar internal substitutents as selective ligands for estrogen receptor beta

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

Research output: Contribution to journalArticle

Abstract

To create estrogen receptor beta (ERβ)-selective ligands with improved biological characteristics, we have extended our investigations of structurally simple bibenzyl-core ligands by preparing a series of compounds in which one phenol is replaced by a 3-hydroxypyridine ring. These phenethyl pyridines were obtained by picoline anion alkylation, and compounds with different patterns of alkyl substitution on the central two carbon units were prepared. Binding affinities for ERα and ERβ were determined, and ligands with promising affinities and selectivities for ERβ were further tested for their gene transcriptional activity. Several compounds had high affinity selectivity and good potency selectivity in transcription assays. This study advances our understanding of compounds having ER-subtype selectivity and will help to direct efforts in developing novel ER ligands.

Original languageEnglish (US)
Pages (from-to)3560-3570
Number of pages11
JournalEuropean Journal of Medicinal Chemistry
Volume44
Issue number9
DOIs
StatePublished - Sep 1 2009

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Keywords

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

ASJC Scopus subject areas

  • Pharmacology
  • Drug Discovery
  • Organic Chemistry

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