Himbacine derived thrombin receptor antagonists: Discovery of a new tricyclic core

The synthesis and biological activity of a novel series of thrombin receptor antagonists is described. This series of compounds showed excellent in vitro and in vivo potency. The most potent compound 40 had an IC50 of 7.6 nM and showed robust inhibition of platelet aggregation in a cynomolgus monkey model after oral administration.

Graphical abstractThe synthesis and biological activity of a novel series of thrombin receptor antagonists is described. This series of compounds showed excellent in vitro and in vivo potency. The most potent compound (40) had an IC50 of 7.6 nM and showed robust inhibition of platelet aggregation in a cynomolgus monkey model after oral administration.Figure optionsDownload full-size imageDownload as PowerPoint slide