2. Academic Validation
  3. Discovery of the Soluble Guanylate Cyclase Stimulator Vericiguat (BAY 1021189) for the Treatment of Chronic Heart Failure

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

Affiliation

  • 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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