Deconstructing estradiol: Removal of B-ring generates compounds which are potent and subtype-selective estrogen receptor agonists

被引：18

作者：

Asim, Mohammud ^{[2
]}

El-Salfiti, Mohamed ^{[2
]}

Qian, Yiming ^{[2
]}

Choueiri, Christine ^{[2
]}

Salari, Samira ^{[2
]}

Cheng, James ^{[2
]}

Shadnia, Hooman ^{[1
]}

Bal, Manpartap ^{[1
]}

Pratt, M. A. Christine ^{[3
]}

Carlson, Kathryn E. ^{[4
]}

Katzenellenbogen, John A. ^{[4
]}

Wright, James S. ^{[1
]}

Durst, Tony ^{[2
]}

机构：

[1] Carleton Univ, Dept Chem, Ottawa, ON K1S 5B6, Canada

[2] Univ Ottawa, Dept Chem, Ottawa, ON K1N 6N5, Canada

[3] Univ Ottawa, Dept Cellular & Mol Med, Ottawa, ON K1H 8M5, Canada

[4] Univ Illinois, Dept Chem, Urbana, IL 61801 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2009年 / 19卷 / 04期

基金：

加拿大自然科学与工程研究理事会; 美国国家卫生研究院;

关键词：

Hormone replacement therapy; Synthetic hormones; Estradiol; Estrogen receptor selectivity; Quinone metabolites; BETA; MECHANISMS;

D O I：

10.1016/j.bmcl.2008.12.080

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Estradiol and related estrogens have been widely used as supplements to relieve menopausal symptoms, but they lead to an increased risk of breast and endometrial cancer. Here we report the synthesis of a new family of compounds where we have removed the B-ring from the steroid ABCD structure, and functionalized the A-ring. These A-CD compounds show a preferential affinity for the estrogen receptor subtype ER beta. Some show binding affinities which are greater than estradiol. The presence of electron-withdrawing substituents on the A-ring should reduce the tendency of these compounds to form carcinogenic metabolites, so they might lead to a safer approach to hormone replacement therapy. (C) 2009 Elsevier Ltd. All rights reserved.

引用

页码：1250 / 1253

页数：4

共 19 条

[1] Potential mechanisms of estrogen quinone carcinogenesis [J].