Synthesis and evaluation of 17α-(dimethylphenyl)vinyl estradiols as probes of the estrogen receptor-α ligand binding domain

被引：12

作者：

Hanson, Robert N. ^{[1
]}

McCaskill, Emmett ^{[1
]}

Tongcharoensirikul, Pakamas ^{[1
]}

Dilis, Robert ^{[1
]}

Labaree, David ^{[2
]}

Hochberg, Richard B. ^{[2
]}

机构：

[1] Northeastern Univ, Dept Chem & Chem Biol, Boston, MA 02115 USA

[2] Yale Univ, Sch Med, Dept Obstet & Gynecol, New Haven, CT 06520 USA

来源：

STEROIDS | 2012年 / 77卷 / 05期

基金：

美国国家科学基金会; 美国国家卫生研究院;

关键词：

Steroidal estrogens; Estrogen receptor; Ligand binding domain; Synthesis; Molecular modeling; Binding assay; BETA; HOMOLOGY; DESIGN;

D O I：

10.1016/j.steroids.2012.01.003

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

As part of our program to explore the influence of small structural modifications on the biological response of the estrogen receptor-alpha (ER alpha), we prepared and evaluated a series of mono-and di-substituted phenyl vinyl estradiols. The target compounds were prepared in 45-80% yields using the Stille coupling reaction and evaluated using competitive binding analysis with the ER alpha-ligand binding domain (hER alpha-LBD) and estrogenic activity (induction of alkaline phosphatase in Ishikawa cells). Results indicated that the 2,4- and 2,5-dimethyl derivatives, 5b and 5c, had the highest relative binding affinity (RBA = 20.5 and 37.3%) and relative stimulatory activity (RSA = 101.0% and 12.3%) of the di-methyl series. (C) 2012 Elsevier Inc. All rights reserved.

引用

页码：471 / 476

页数：6

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