bay-60-4552 and Heart-Failure

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.

Topics: Administration, Intravenous; Administration, Oral; Animals; Blood Pressure; Chemistry Techniques, Synthetic; Dogs; Heart Failure; Hepatocytes; Heterocyclic Compounds, 2-Ring; Humans; Male; NG-Nitroarginine Methyl Ester; Pyrimidines; Rats, Transgenic; Rats, Wistar; Soluble Guanylyl Cyclase; Structure-Activity Relationship