Structure-activity relationships of estrogenic ligands: synthesis and evaluation of (17 alpha, 20E)- and (17 alpha, 20Z)-21-halo-19-norpregna-1,3,5(10),20-tetraene-3,17 beta-diols.
Structure-activity relationships of estrogenic ligands: synthesis and evaluation of (17 alpha, 20E)- and (17 alpha, 20Z)-21-halo-19-norpregna-1,3,5(10),20-tetraene-3,17 beta-diols.
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雌激素配体的结构-活性关系：(17 α, 20E)-和(17 α, 20Z)-21-halo-19-norpregna-1,3,5(10),20-tetraene-3的合成和评估，
DOI：
10.1021/jm00113a012
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发表时间：
1991
影响因子：
7.3
通讯作者：
Hanson,RN
中科院分区：
文献类型：
--
作者：
Napolitano,E;Fiaschi,R;Hanson,RN
As part our program to probe the molecular requirement for estrogen-receptor binding we undertook the synthesis and evaluation of the 17a, E and 17a, Z halovinyl estradiols. By use of an improved variationof the existing synthetic strategy, the targeted compounds were prepared stereospecifically and in 92-98% yields from the corresponding Ylafi or 17, Z [(tri-n-butylstannyl) vinyl] estradiol 3-acetates. The novel estradiol derivatives were evaluated for their relative binding affinity (RBA) for the estrogen receptor with use of a rat uterine preparation. The results demonstrated a marked difference between the E and Z isomers and among the halogen employed. The Z isomers possessed significantly higher RBA values and the larger halogens (I, Br) were more effective than the smaller Cl substituent. These results modify the previous interpretations of estrogen-receptor binding for steroidal ligands. As a result, our design of (radio) halogenated ligands will incorporate this concern for Z vs E stereochemistry.
