Synthesis and estrogen receptor binding of novel 11 beta-substituted estra-1,3,5(10)-triene-3,17 beta-diols.
As part of our program to develop estrogenic radioligands for use in nuclear medicine, a study was undertaken to investigate the effect of substituents on the receptor affinity of putative radiochemicals. In the study a synthetic strategy directed toward the introduction of an 11 beta-(fluoroethyl) substituent was devised. The target compound 9 was prepared via a five-step procedure starting from 11 beta-vinylestrone 3-acetate (4) in an overall 43% yield. The stereochemistry of the 11 beta-vinyl moiety was established by X-ray crystallography. The final product and several analogues, 11 beta-ethyl-, -vinyl-, and (hydroxyethyl)estradiols (11, 5, and 12), were evaluated for their estrogen receptor binding affinity. The results indicate that the target compound and several 11 beta-substituted analogues possess relative binding affinities greater than of estradiol and its 16 alpha-fluorinated derivatives. The manner in which the target compound 9 was prepared is amenable to use with 18F incorporation.
Hanson
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Section of Medicinal Chemistry, College of Pharmacy & Allied Health Professions, Northeastern University, Boston, Massachusetts 02114.
Napolitano
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Fiaschi
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D000818:Animals; D001667:Binding, Competitive; D055598:Chemical Phenomena; D002621:Chemistry; D003460:Crystallization; D003600:Cytosol / Q000378:metabolism; D004958:Estradiol / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism; D005260:Female; D005462:Fluorine Radioisotopes; D008968:Molecular Conformation; D015394:Molecular Structure; D051381:Rats; D011960:Receptors, Estrogen / Q000378:metabolism*; D012756:Sheep; D013329:Structure-Activity Relationship; D014599:Uterus / Q000378:metabolism; D014961:X-Ray Diffraction
D005462:Fluorine Radioisotopes; D011960:Receptors, Estrogen; C066618:11-(2-fluoroethyl)estradiol; D004958:Estradiol