Design and optimization of new piperidines as renin inhibitors

A novel series of piperidine-based renin inhibitors with improved efficacy in a double transgenic rat model is reported. Piperidines such as 41 (IC 50 in plasma = 5.6 nM) showed high efficacy on blood pressure reduction (−36 mmHg) at low dose (3 mg/kg). The discovery of a new series of piperidine-based renin inhibitors is described herein. SAR optimization upon the P3 renin sub-pocket is described, leading to the discovery of 9 and 41, two bioavailable renin inhibitors orally active at low doses in a transgenic rat model of hypertension.