Synthesis and Estrogen Receptor Binding of Novel 11β-Substituted Estra-1,3,5(10)-triene-3,17β-diols

Article abstract of DOI:10.1021/jm00174a010

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 11β-(fluoroethyl) substituent was devised.The target compound 9 was prepared via a five-step procedure starting from 11β-vinylestrone 3-acetate (4) in an overall 43percent yield.The final product and several analogues, 11β-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 11β-substituted analogues possess relative binding affinities greater than of estradiol and its 16α-fluorinated derivatives.The manner in which the target compound 9 was prepared is amenable to use with 18F incorporation.