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：
美国国家卫生研究院; 美国国家科学基金会;
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
收藏
页码：471 / 476
页数：6
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