Stereochemical probes for the estrogen receptor: synthesis and receptor binding of (17 alpha,20E/Z)-21-phenyl-19-norpregna-1,3,5(10), 20-tetraene-3,17 beta-diols

Steroids. 1996 Dec;61(12):718-22. doi: 10.1016/s0039-128x(96)00201-2.

Abstract

Previous studies from our laboratory using 17 alpha-E- and 17 alpha-Z-halovinyl and phenylthiovinyl estradiols demonstrated a marked preference for the Z stereochemistry and a significant steric tolerance for the Z-vinyl substituent. To further explore the extent of that stereochemical preference and steric tolerance we have prepared stereoselectively the 17 alpha-E- and 17 alpha-Z-phenylvinyl estradiols (E- and Z-styrylestradiols). The results, in addition to demonstrating a facile preparation of the target compounds, supported the previously observed stereochemical and steric effects. The relative binding affinities for the Z isomer were 3-4 fold greater than the E isomer at both 4 degrees C and 25 degrees C, and only one-half to one-fourth those of estradiol under similar conditions. The developing model for ligand-accessible space within the estrogen receptor suggests that Z-phenylvinyl estradiols may provide interesting and useful probes for mapping the receptor.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Binding Sites
  • Binding, Competitive
  • Estradiol / analogs & derivatives*
  • Estradiol / chemistry
  • Estradiol / metabolism*
  • Models, Molecular
  • Molecular Structure
  • Receptors, Estrogen / chemistry
  • Receptors, Estrogen / metabolism*
  • Structure-Activity Relationship

Substances

  • Receptors, Estrogen
  • Estradiol