Selective and potent agonists for estrogen receptor beta derived from molecular refinements of salicylaldoximes

Eur J Med Chem. 2011 Jun;46(6):2453-62. doi: 10.1016/j.ejmech.2011.03.030. Epub 2011 Mar 23.


In a continuing effort to improve the subtype selectivity and agonist potency of estrogen receptor β (ERβ) ligands, we have designed and developed a thus far unexplored structural series obtained by molecular refinements of monoaryl-substituted salicylaldoximes (Salaldox B). The most interesting compounds in this series (2c, d) show remarkably high ERβ-binding affinities, with Ki values reaching the sub-nanomolar range (Ki=0.38 nM for 2c and 0.57 nM for 2d), and have very high levels of ERβ-subtype selectivity. Both compounds show a potent full agonist character on ERβ (EC50=0.23 nM for 2c and 1.3 nM for 2d). Furthermore, 2d shows a remarkable functional subtype selectivity, with a β/α transcription potency ratio 50-fold higher than that of estradiol.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Dose-Response Relationship, Drug
  • Estrogen Receptor beta / agonists*
  • Humans
  • Models, Molecular
  • Molecular Structure
  • Oximes / chemical synthesis
  • Oximes / chemistry
  • Oximes / pharmacology*
  • Quantum Theory
  • Stereoisomerism
  • Structure-Activity Relationship


  • Estrogen Receptor beta
  • Oximes
  • salicylaldoxime