Identification of a new biaryl scaffold generating potent renin inhibitors

The discovery and SAR of a series of potent renin inhibitors possessing a novel biaryl scaffold are described herein. Molecular modeling revealed that the cyclopropylamide spacer present in 1 can be replaced by a simple, substituted aromatic ring such as a toluene in 2. The resulting compounds exhibit subnanomolar renin IC50 and good oral bioavailability in rats.

Graphical abstractThe discovery and SAR of a series of potent renin inhibitors possessing a novel biaryl scaffold are described herein. Molecular modeling revealed that the cyclopropylamide spacer present in our lead compound can be replaced by a simple, substituted aromatic ring such as a toluene. The resulting compounds exhibit subnanomolar renin IC50 and good oral bioavailability in rats.Figure optionsDownload full-size imageDownload as PowerPoint slide