Renin inhibitors. Dipeptide analogues of angiotensinogen utilizing a structurally modified phenylalanine residue to impart proteolytic stability.
A series of renin inhibitors have been prepared and evaluated for their susceptibility to cleavage by the serine protease chymotrypsin. The compounds were designed by consideration of the structural requirements in the active-site region of renin and chymotrypsin. By systematic alteration of the P3 phenylalanine residue, compounds with varying degrees of renin inhibitory potency and chymotrypsin susceptibility were obtained. Selected analogues from this group were examined in vivo for both their hypotensive effects and metabolic patterns.
D000808:Angiotensinogen / Q000031:analogs & derivatives*; D000818:Animals; D001665:Binding Sites; D001794:Blood Pressure / Q000187:drug effects; D055598:Chemical Phenomena; D002621:Chemistry; D002918:Chymotrypsin; D004151:Dipeptides / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology; D015195:Drug Design; D004355:Drug Stability; D005026:Ethylene Glycols / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology; D000882:Haplorhini; D006801:Humans; D010649:Phenylalanine / Q000031:analogs & derivatives*; D051381:Rats; D013329:Structure-Activity Relationship; D000092502:Renin Inhibitors
D000808:Angiotensinogen; D002918:Chymotrypsin; D004151:Dipeptides; D005026:Ethylene Glycols; D010649:Phenylalanine; D000092502:Renin Inhibitors