Discovery of new selective glucocorticoid receptor agonist leads

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• 作者：Markus Berger^a ; ^{markus.berger@bayer.com} ; Hartmut Rehwinkel^a ; Norbert Schmees^a ; Heike Schä ; cke^b ; Karl Edman^c ; Lisa Wissler^c ; Andreas Reichel^d ; Stefan Jaroch^e
• 关键词：Glucocorticoid ; SEGRA ; Transrepression ; Transactivation ; Tetrahydronaphthalene ; Amino alcohol
• 刊名：Bioorganic & Medicinal Chemistry Letters
• 出版年：2017
• 出版时间：1 February 2017
• 年：2017
• 卷：27
• 期：3
• 页码：437-442
• 全文大小：971 K
• 卷排序：27

文摘

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.