Phenylbenzenesulfonates and -sulfonamides as 17β-hydroxysteroid dehydrogenase type 2 inhibitors: Synthesis and SAR-analysis

被引：5

作者：

Vuorinen, Anna ^{[1
,2
,3
]}

Engeli, Roger T. ^{[3
]}

Leugger, Susanne ^{[3
]}

Kreutz, Christoph R. ^{[4
,5
]}

Schuster, Daniela ^{[1
,2
]}

Odermatt, Alex ^{[3
]}

Matuszczak, Barbara ^{[1
,2
]}

机构：

[1] Univ Innsbruck, Inst Pharm Pharmaceut Chem, Innrain 80-82, A-6020 Innsbruck, Austria

[2] Univ Innsbruck, CMBI, Innrain 80-82, A-6020 Innsbruck, Austria

[3] Univ Basel, Div Mol & Syst Toxicol, Dept Pharmaceut Sci, Klingelbergstr 50, CH-4056 Basel, Switzerland

[4] Univ Innsbruck, Inst Organ Chem, Innrain 80-82, A-6020 Innsbruck, Austria

[5] Univ Innsbruck, Ctr Mol Biosci CMBI, Innrain 80-82, A-6020 Innsbruck, Austria

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2017年 / 27卷 / 13期

基金：

瑞士国家科学基金会;

关键词：

17; beta-HSD2; Inhibitor; Osteoporosis; Virtual screening; Estrogen; 11-BETA-HYDROXYSTEROID DEHYDROGENASE TYPE-2; POSTMENOPAUSAL WOMEN; OSTEOPOROSIS; DISCOVERY; EXPRESSION; LOCALIZATION; HEPATOCYTES; MANAGEMENT; TOXICITY; PLACENTA;

D O I：

10.1016/j.bmcl.2017.05.005

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

17 beta-Hydroxysteroid dehydrogenase type 2 (17 beta-HSD2) converts the potent estrogen estradiol into the weakly active keto form estrone. Because of its expression in bone, inhibition of 17 beta-HSD2 provides an attractive strategy for the treatment of osteoporosis, a condition that is often caused by a decrease of the active sex steroids. Currently, there are no drugs on the market targeting 17 beta-HSD2, but in multiple studies, synthesis and biological evaluation of promising 17 beta-HSD2 inhibitors have been reported. Our previous work led to the identification of phenylbenzenesulfonamides and -sulfonates as new 17 beta HSD2 inhibitors by ligand-based pharmacophore modeling and virtual screening. In this study, new molecules representing this scaffold were synthesized and tested in vitro for their 17 beta-HSD2 activity to derive more profound structure-activity relationship rules. (C) 2017 Elsevier Ltd. All rights reserved.

引用

页码：2982 / 2985

页数：4

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