Iminopyrimidinones: A novel pharmacophore for the development of orally active renin inhibitors

The development of renin inhibitors with favorable oral pharmacokinetic profiles has been a longstanding challenge for the pharmaceutical industry. As part of our work to identify inhibitors of BACE1, we have previously developed iminopyrimidinones as a novel pharmacophore for aspartyl protease inhibition. In this letter we describe how we modified substitution around this pharmacophore to develop a potent, selective and orally active renin inhibitor.

Graphical abstractThe development of renin inhibitors with favorable oral pharmacokinetic profiles has been a longstanding challenge for the pharmaceutical industry. As part of our work to identify inhibitors of BACE1, we have previously developed iminopyrimidinones as a novel pharmacophore for aspartyl protease inhibition. In this Letter we describe how we modified substitution around this pharmacophore to develop a potent, selective and orally active renin inhibitor.Figure optionsDownload full-size imageDownload as PowerPoint slide