1. Discovery of the Soluble Guanylate Cyclase Stimulator Vericiguat (BAY 1021189) for the Treatment of Chronic Heart Failure
- Author
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Volkhart Mj Li, Eva-Maria Becker-Pelster, Jens Ackerstaff, Michael Gerisch, Klemens Lustig, Armin Kern, Hubert Trübel, Peter Dr Fey, Andreas Knorr, Peter Sandner, Nils Griebenow, Axel Kretschmer, Gorden Redlich, Hanna Tinel, Frank Wunder, Karl-Heinz Schlemmer, Johannes-Peter Stasch, Hartmut Schirok, Rolf Jautelat, Volker Geiss, Thomas Mondritzki, Walter Kroh, Markus Follmann, Alexander Straub, Dieter Lang, and Joachim Mittendorf
- Subjects
Male ,0301 basic medicine ,Administration, Oral ,Blood Pressure ,Chemistry Techniques, Synthetic ,030204 cardiovascular system & hematology ,Pharmacology ,Heterocyclic Compounds, 2-Ring ,Riociguat ,Structure-Activity Relationship ,03 medical and health sciences ,Dogs ,Soluble Guanylyl Cyclase ,0302 clinical medicine ,Drug Discovery ,medicine ,Animals ,Humans ,Rats, Wistar ,Heart Failure ,Oxidative metabolism ,Chemistry ,Treatment options ,medicine.disease ,Soluble Guanylate Cyclase Stimulator ,Pulmonary hypertension ,NG-Nitroarginine Methyl Ester ,Pyrimidines ,030104 developmental biology ,Heart failure ,Hepatocytes ,Molecular Medicine ,Administration, Intravenous ,Vericiguat ,Rats, Transgenic ,Once daily ,medicine.drug - 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.
- Published
- 2017