Renin inhibitors Improvements in the stability and biological activity of small peptides containing novel Leu‐Val replacements

Abstract

We have designed a novel class of potent (0.3–7 nM) renin inhibitors which contain a dihydroxyethylene replacement for what is formally the Leu 1O -Val 11 amide bond. Good potency (0.6 nM), water solubility (> 10 mg/ml at 37°C), stability toward degradation by chymotrypsin ( t 1 2 =82O min), and in vivo activity in a primate model (15% drop in mean arterial pressure in association with complete inhibition of plasma renin activity) are properties which have been incorporated into compound 10 , an interesting new agent to be used in the study of hypertension.