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

Eur J Med Chem. 2009 Sep;44(9):3560-70. doi: 10.1016/j.ejmech.2009.03.013. Epub 2009 Mar 24.


To create estrogen receptor beta (ERbeta)-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 ERalpha and ERbeta were determined, and ligands with promising affinities and selectivities for ERbeta 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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Cell Line, Tumor
  • Endometrial Neoplasms / genetics
  • Endometrial Neoplasms / metabolism
  • Estrogen Receptor alpha / genetics
  • Estrogen Receptor alpha / metabolism
  • Estrogen Receptor beta / genetics*
  • Estrogen Receptor beta / metabolism*
  • Female
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Ligands
  • Molecular Structure
  • Protein Binding
  • Pyridines / chemistry*
  • Pyridines / pharmacology*
  • Transcription, Genetic / drug effects


  • Estrogen Receptor alpha
  • Estrogen Receptor beta
  • Ligands
  • Pyridines