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 tolerance of the estrogen receptor for the 17 alpha-phenylselenovinyl substituent and the enhancement of affinity imparted by the 11 beta-vinyl moiety. Our recent publication suggested that the two groups could be combined within a single structure and retain high affinity for the estrogen receptor. As a result, we have prepared in good overall yields the E- and Z-isomers of 11 beta-vinyl-17 alpha-phenylselenovinyl estradiol. Evaluation of the new steroids with receptor isolated from lamb cytosol indicated that both isomers are poorer ligands than estradiol at 4 degrees C, but both are better than estradiols. 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 observation that, unlike previous isomer pairs, the E-isomer possessed a greater affinity than the Z-isomer. The results suggest that relatively small changes in structure may impart significant differences in the interactions with the receptor and provide the basis for further ligand design.
Hanson
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Department of Pharmaceutical Sciences, Bouve College of Pharmacy and Health Sciences, Northeastern University, Boston, Massachusetts, USA.
Napolitano
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E
Fiaschi
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R
D001667:Binding, Competitive; D004958:Estradiol / Q000138:chemical synthesis / Q000378:metabolism*; D007536:Isomerism; D008024:Ligands; D011960:Receptors, Estrogen / Q000378:metabolism*
D008024:Ligands; D011960:Receptors, Estrogen; D004958:Estradiol