2. Academic Validation
  3. Discovery of the potent non-steroidal glucocorticoid receptor modulator BAY 1003803 as clinical candidate

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

  • Bioorg Med Chem Lett. 2020 Aug 15;30(16):127298. doi: 10.1016/j.bmcl.2020.127298.
Markus Berger 1,  Ekkehard May 2,  Hartmut Rehwinkel 3,  Heike Schäcke 4,  Roland Neuhaus 5,  Antje Rottmann 5,  Thomas M Zollner 4,  Stefan Jaroch 6
Affiliations

Affiliations

  • 1 Medicinal Chemistry Berlin, Research & Development, Pharmaceuticals, Bayer AG, D-13353 Berlin, Germany. Electronic address: [email protected].
  • 2 Cross Indication Research, Innovation Campus Berlin, Research & Development, Pharmaceuticals, Bayer AG, D-13353 Berlin, Germany.
  • 3 Medicinal Chemistry Berlin, Research & Development, Pharmaceuticals, Bayer AG, D-13353 Berlin, Germany.
  • 4 Therapeutic Area Endocrinology, Metabolism and Reproductive Health, Research & Development, Pharmaceuticals, Bayer AG, D-13353 Berlin, Germany.
  • 5 Drug Metabolism and Pharmacokinetics, Research & Development, Pharmaceuticals, Bayer AG, D-13353 Berlin, Germany.
  • 6 Open Innovation, Research & Development, Pharmaceuticals, Bayer AG, D-13353 Berlin, Germany.
PMID: 32631518 DOI: 10.1016/j.bmcl.2020.127298
Abstract

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.

Keywords

Amino alcohol; Glucocorticoid; SEGRA; Transactivation; Transrepression.

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