Estrogen receptor binding characteristics of 1,11 beta-ethanoestradiol: effect of a 1,11 beta-bridge on steroidal estrogen.
As part of an ongoing program to develop high affinity estrogenic ligands we have synthesized the 11 beta-vinyl, 11 beta-ethyl- and 1,11 beta-ethanoestradiols. Because the 1,11 beta-ethano-estradiol had not been previously reported in the literature, the investigation of its receptor binding characteristics would provide valuable insight into the effect of 1/11 beta-substitution. The data obtained in this study indicate that although significant estrogen receptor affinity is present for the 1,11 beta-ethano derivative, the RBA values, 5-22.4%, were far less than those observed (5-300-fold less) for the corresponding 11 beta-ethyl and 11 beta-vinyl estradiols and less than those for the 1-methyl and 11 beta-methyl estradiols. These results suggest that the orientation that the 11 beta-substituent must occupy is directed away from the A-ring and that substituents in the 1-11 pocket produce a detrimental effect on receptor interactions.
Napolitano
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E
Section of Medicinal Chemistry, College of Pharmacy and Allied Health Professions, Northeastern University, Boston, MA 02115.
Fiaschi
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R
Hanson
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RN
D000818:Animals; D001667:Binding, Competitive; D004958:Estradiol / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000378:metabolism; D005260:Female; D007202:Indicators and Reagents; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D009904:Optical Rotation; D011960:Receptors, Estrogen / Q000378:metabolism*; D012756:Sheep; D014599:Uterus / Q000378:metabolism
D007202:Indicators and Reagents; D011960:Receptors, Estrogen; C066815:1,11-ethanoestradiol; D004958:Estradiol