|
|||||
|
|
Discovery of new selective glucocorticoid receptor agonist leads |
|
| Authors: | Markus Berger Hartmut Rehwinkel Norbert Schmees Heike Schäcke Karl Edman Lisa Wissler Andreas Reichel Stefan Jaroch |
| Affiliation: | 1. Medicinal Chemistry Berlin, Candidate Generation & External Innovation, Drug Discovery, Bayer Pharma AG, D-13353 Berlin, Germany;2. Gynecological Therapies Berlin, Global Therapeutic Research, Drug Discovery, Bayer Pharma AG, D-13353 Berlin, Germany;3. Discovery Sciences, Innovative Medicines and Early Development Biotech Unit, AstraZeneca, Pepparedsleden 1, Mölndal 431 83, Sweden;4. Research Pharmacokinetics, Early Development, Drug Discovery, Bayer Pharma AG, D-13353 Berlin, Germany;5. Global External Innovation & Alliances, Candidate Generation & External Innovation, Drug Discovery, Bayer Pharma AG, D-13353 Berlin, Germany |
| Abstract: | 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. |
| Keywords: | Glucocorticoid SEGRA Transrepression Transactivation Tetrahydronaphthalene Amino alcohol |
| 本文献已被 ScienceDirect 等数据库收录！ | |