Discovery of the Soluble Guanylate Cyclase Stimulator Vericiguat (BAY 1021189) for the Treatment of Chronic Heart Failure

  • J Med Chem. 2017 Jun 22;60(12):5146-5161. doi: 10.1021/acs.jmedchem.7b00449.
Markus Follmann  1 ,  Jens Ackerstaff  1 ,  Gorden Redlich  1 ,  Frank Wunder  1 ,  Dieter Lang  1 ,  Armin Kern  1 ,  Peter Fey  1 ,  Nils Griebenow  1 ,  Walter Kroh  1 ,  Eva-Maria Becker-Pelster  1 ,  Axel Kretschmer  1 ,  Volker Geiss  1 ,  Volkhart Li  1 ,  Alexander Straub  1 ,  Joachim Mittendorf  1 ,  Rolf Jautelat  1 ,  Hartmut Schirok  1 ,  Karl-Heinz Schlemmer  1 ,  Klemens Lustig  1 ,  Michael Gerisch  1 ,  Andreas Knorr  1 ,  Hanna Tinel  1 ,  Thomas Mondritzki  1 ,  Hubert Trübel  1 ,  Peter Sandner  1 ,  Johannes-Peter Stasch  1
Affiliations
  • 1. Drug Discovery, Bayer AG , Aprather Weg 18a, 42113 Wuppertal, Germany.
PMID: 28557445 DOI: 10.1021/acs.jmedchem.7b00449
Abstract

The first-in-class soluble Guanylate Cyclase (sGC) stimulator riociguat was recently introduced as a novel treatment option for Pulmonary Hypertension. Despite its outstanding pharmacological profile, application of riociguat in other cardiovascular indications is limited by its short half-life, necessitating a three times daily dosing regimen. In our efforts to further optimize the compound class, we have uncovered interesting structure-activity relationships and were able to decrease oxidative metabolism significantly. These studies resulting in the discovery of once daily sGC stimulator vericiguat (compound 24, BAY 1021189), currently in phase 3 trials for chronic Heart Failure, are now reported.

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