Novel small molecule bradykinin B1 receptor antagonists. Part 1: Benzamides and semicarbazides

The synthesis and SAR of two series of bradykinin B1 receptor antagonists is described. The benzamide moiety proved to be a suitable replacement for the aryl ester functionality of biaryl based antagonists. In addition, it was found that semicarbazides can effectively replace cyclopropyl amino acids. The compounds with the best overall profile were biaryl semicarbazides which display high antagonistic activity, low Caco-2 efflux and high oral bioavailability in the rat.

Graphical abstractBenzamides and semicarbazides are introduced as new classes of bradykinin B1 receptor antagonists. The best compounds feature excellent pharmacokinetic properties in the rat.Figure optionsDownload full-size imageDownload as PowerPoint slide