NOVEL HIGH-AFFINITY STEROIDAL ESTROGENIC LIGANDS - SYNTHESIS AND RECEPTOR-BINDING OF 11-BETA-VINYL-17-ALPHA-E Z-PHENYLSELENOVINYL ESTRADIOLS/

previous studies from our laboratory demonstrated separately the toler ance of the estrogen receptor for the 17 alpha-phenylselenovinyl subst ituent and the enhancement of affinity imparted by the 11 beta-vinyl m oiety. Our recent publication suggested that the two groups could be c ombined within a single structure and retain high affinity for the est rogen receptor. As a result we have prepared in good overall yields th e E- and Z-isomers of 11 beta-vinyl-17 alpha-phenylselenovinyl estradi ol. Evaluation of the new steroids with receptor isolated from lamb cy tosol indicated that both isomers are poorer ligands than estradiol at 4 degrees C, but both are better than estradiol at 25 degrees C. This behavior had not been observed for the 11 beta-unsubstituted 17 alpha -E/Z phenylselenovinyl estradiols. Of particular interest was the obse rvation that unlike previous isomer pairs, the E-isomer possessed a gr eater affinity than the Z-isomer. The results suggest that relatively small changes iii structure may impart significant differences in the interactions with the receptor and provide the basis for further ligan d design. (C) 1998 by Elsevier Science Inc.