1. Academic Validation
  2. Discovery of BAY 94-8862: a nonsteroidal antagonist of the mineralocorticoid receptor for the treatment of cardiorenal diseases

Discovery of BAY 94-8862: a nonsteroidal antagonist of the mineralocorticoid receptor for the treatment of cardiorenal diseases

  • ChemMedChem. 2012 Aug;7(8):1385-403. doi: 10.1002/cmdc.201200081.
Lars Bärfacker 1 Alexander Kuhl Alexander Hillisch Rolf Grosser Santiago Figueroa-Pérez Heike Heckroth Adam Nitsche Jens-Kerim Ergüden Heike Gielen-Haertwig Karl-Heinz Schlemmer Joachim Mittendorf Holger Paulsen Johannes Platzek Peter Kolkhof
Affiliations

Affiliation

  • 1 Bayer Pharma AG, Medicinal Chemistry Wuppertal, 42096 Wuppertal, Germany. lars.baerfacker@bayer.com
Abstract

Aldosterone is a hormone that exerts manifold deleterious effects on the kidneys, blood vessels, and heart which can lead to pathophysiological consequences. Inhibition of the Mineralocorticoid Receptor (MR) is a proven therapeutic concept for the management of associated diseases. Use of the currently marketed MR antagonists spironolactone and eplerenone is restricted, however, due to a lack of selectivity in spironolactone and the lower potency and efficacy of eplerenone. Several pharmaceutical companies have implemented programs to identify drugs that overcome the known liabilities of steroidal MR antagonists. Herein we disclose an extended SAR exploration starting from cyano-1,4-dihydropyridines that were identified by high-throughput screening. Our efforts led to the identification of a dihydronaphthyridine, BAY 94-8862, which is a potent, selective, and orally available nonsteroidal MR antagonist currently under investigation in a clinical phase II trial.

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