Substrate Analogue Renin Inhibitors Containing Replacements of Histidine in P₂ or Isosteres of the Amide Bond Between P₃ and P₂ Sites

Abstract

The search for orally active renin inhibitors as therapeutic agents continues to represent a challenging target for medicinal chemists.¹ Analogues of the angiotensinogen region flanking the bond split by renin have turned out to be very potent and specific inhibitors of renin. However, the high affinity of these angiotensinogen analogues for human renin is often associated with fast hydrolysis between P₃ and P₂ sites by the intestinal serine protease chymotrypsin.²