SYNTHESIS AND ESTROGEN-RECEPTOR BINDING OF NOVEL 11-BETA-SUBSTITUTED ESTRA-1,3,5(10)-TRIENE-3,17-BETA-DIOLS

被引：21

作者：

HANSON, RN ^{[1
]}

NAPOLITANO, E ^{[1
]}

FIASCHI, R ^{[1
]}

ONAN, KD ^{[1
]}

机构：

[1] NORTHEASTERN UNIV,DEPT CHEM,BOSTON,MA 02114

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 1990年 / 33卷 / 12期

关键词：

D O I：

10.1021/jm00174a010

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

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 43% yield. The stereochemistry of the 11β-vinyl moiety was established by X-ray crystallography. 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. © 1990, American Chemical Society. All rights reserved.

引用

页码：3155 / 3160

页数：6

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