STEREOCHEMICAL PROBES FOR THE ESTROGEN-RECEPTOR - SYNTHESIS AND RECEPTOR-BINDING OF (17-ALPHA,20E 9-NORPREGNA-1,3,5(10),20-TETRAENE-3,17-BETA-DIOLS/

Previous studies from our laboratory using 17 alpha-E- and 17 alpha-Z- halovinyl and phenylthiovinyl estradiols demonstrated a marked prefere nce for the Z stereochemistry and a significant steric tolerance for t he Z-vinyl substituent. To further explore the extent of that stereoch emical preference and steric tolerance we have prepared stereoselectiv ely the 17 alpha-E- and 17 alpha-Z-phenylvinyl estradiols (E- and Z-st yrylestradiols). The results, in addition to demonstrating a facile pr eparation of the target compounds, supported the previously observed s tereochemical 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 estradio l under similar conditions. The developing model for ligand-accessible space within the estrogen receptor suggests that Z-phenylvinyl estrad iols may provide interesting and useful probes for mapping the recepto r. (C) 1996 by Elsevier Science Inc.