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.