Design and synthesis of a potent and specific renin inhibitor with a prolonged duration of action in vivo
摘要：
A structure-activity analysis of peptides containing backbone C alpha-methyl and N alpha-methyl modifications led to the discovery of potent renin inhibitors with high metabolic stability. In vitro, Boc-Pro-Phe-N alpha-MeHis-Leu psi-[CHOHCH2]Val-Ile-Amp (XII) is a potent inhibitor of human plasma renin with IC50 of 0.26 nM. It is a much weaker inhibitor of other aspartic proteases such as porcine pepsin or bovine cathepsin D (IC50 = 6 microM). It was shown not to be degraded by a rat liver homogenate preparation. In vivo, it inhibited plasma renin activity and lowered blood pressure of furosemide-treated cynomolgus monkeys. At a dose of 5 mg/kg iv, the pronounced hypotensive response persisted for greater than 3 h postinfusion.
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DOI：
10.1002/chin.198711301
被引量：
年份：
1986
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