Discovery of new selective glucocorticoid receptor agonist leads

被引：10

作者：

Berger, Markus ^{[1
]}

Rehwinkel, Hartmut ^{[1
]}

Schmees, Norbert ^{[1
]}

Schaecke, Heike ^{[2
]}

Edman, Karl ^{[3
]}

Wissler, Lisa ^{[3
]}

Reichel, Andreas ^{[4
]}

Jaroch, Stefan ^{[5
]}

机构：

[1] Bayer Pharma AG, Med Chem Berlin, Candidate Generat & External Innovat, Drug Discovery, D-13353 Berlin, Germany

[2] Bayer Pharma AG, Gynecol Therapies Berlin, Global Therapeut Res, Drug Discovery, D-13353 Berlin, Germany

[3] AstraZeneca, Discovery Sci, Innovat Med & Early Dev Biotech Unit, Pepparedsleden 1, S-43183 Molndal, Sweden

[4] Bayer Pharma AG, Res Pharmacokinet, Early Dev, Drug Discovery, D-13353 Berlin, Germany

[5] Bayer Pharma AG, Global External Innovat & Alliances, Candidate Generat & External Innovat, Drug Discovery, D-13353 Berlin, Germany

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2017年 / 27卷 / 03期

关键词：

Glucocorticoid; SEGRA; Transrepression; Transactivation; Tetrahydronaphthalene; Amino alcohol; LIGAND-BINDING DOMAIN; MINERALOCORTICOID RECEPTOR; INFLAMMATORY RESPONSES; CRYSTAL-STRUCTURE; MECHANISMS; IDENTIFICATION; THERAPY; RU-486; SKIN;

D O I：

10.1016/j.bmcl.2016.12.047

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

We report on the discovery of two new lead series for the development of glucocorticoid receptor agonists. Firstly, the discovery of tetrahydronaphthalenes led to metabolically stable and dissociated compounds. Their binding mode to the glucocorticoid receptor could be elucidated through an X-ray structure. Closer inspection into the reaction path and analyses of side products revealed a new amino alcohol series also addressing the glucocorticoid receptor and demonstrating strong anti-inflammatory activity in vitro. (C) 2016 Elsevier Ltd. All rights reserved.

引用

页码：437 / 442

页数：6

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