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Editorial Board Chairs: Antonello Mai, Rainer Metternich. Assoc. Editors: David Peralta, Scott Williams (Sr)
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Online ISSN: 1860-7187
July 17, 2012
VIP: Discovery of BAY 94-8862: A Non-Steroidal Antagonist of the Mineralocorticoid Receptor for the Treatment of Cardiorenal Diseases
Lars Bärfacker,* 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
Blockade of the mineralocorticoid receptor (MR) is a validated treatment for chronic heart failure (CHF), a disease that places a heavy burden not only on patients, but also on healthcare resources. Currently available MR antagonists suffer from two substantial drawbacks that limit their benefit in clinical practice, namely, lack of selectivity (in the case of spironolactone) and limited efficacy (in the case of eplerenone). Lars Bärfacker and colleagues at the Bayer Research Center in Wuppertal (Germany) revealed a novel series of non-steroidal MR antagonists based on a 1,4-dihydropyiridine scaffold. The authors provide a detailed structure–activity relationship as well as insight into the underlying pharmacophore model. Their work has culminated in the identification of BAY 94-8862, a potent non-steroidal MR antagonist with outstanding selectivity. BAY 94-8862 is currently in phase II clinical trials for the treatment of CHF patients with renal impairment.
Received February 9, 2012; published online July 12, 2012, DOI: 10.1002/cmdc.201200081.