Discovery of the potent non-steroidal glucocorticoid receptor modulator BAY 1003803 as clinical candidate

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

卷:30

Article

Berger, Markus¹  May, Ekkehard²  Rehwinkel, Hartmut¹  Schaecke, Heike³  Neuhaus, Roland⁴  Rottmann, Antje⁴  Zollner, Thomas M.³  Jaroch, Stefan⁵ 

[1] Bayer AG, Pharmaceut, Res & Dev, Med Chem Berlin, D-13353 Berlin, Germany

[2] Bayer AG, Pharmaceut, Res & Dev, Cross Indicat Res, Innovat Campus Berlin, D-13353 Berlin, Germany

[3] Bayer AG, Pharmaceut, Res & Dev, Metab & Reprod Hlth,Therapeut Area Endocrinol, D-13353 Berlin, Germany

[4] Bayer AG, Pharmaceut, Res & Dev, Drug Metab & Pharmacokinet, D-13353 Berlin, Germany

[5] Bayer AG, Pharmaceut, Res & Dev, Open Innovat, D-13353 Berlin, Germany

关键词: Glucocorticoid;    SEGRA;    Transrepression;    Transactivation;    Amino alcohol;   

DOI  :  10.1016/j.bmcl.2020.127298

来源: Elsevier

【 摘 要 】

We report on the discovery of the new clinical candidate BAY 1003803 as glucocorticoid receptor agonist for the topical treatment of psoriasis or severe atopic dermatitis. In the course of optimizing the amino alcohol series as a highly potent new non-steroidal lead structure, considerations were made as to how physicochemical properties and safety concerns relate to structural motifs. BAY 1003803 demonstrates strong anti-inflammatory activity in vitro paired with a pharmacokinetic profile suitable for topical application.

【 授权许可】

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