Hanson R N, Napolitano E, Fiaschi R
Section of Medicinal Chemistry, College of Pharmacy & Allied Health Professions, Northeastern University, Boston, Massachusetts 02114.
J Med Chem. 1990 Dec;33(12):3155-60. 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 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.
