Angiotensin-converting enzyme inhibitors: Synthesis and biological activity of N-substituted tripeptide inhibitors.
- 1 January 1990
- journal article
- research article
- Published by Pharmaceutical Society of Japan in CHEMICAL & PHARMACEUTICAL BULLETIN
- Vol. 38 (1) , 110-115
- https://doi.org/10.1248/cpb.38.110
Abstract
A new series of highly potent angiotensin-converting enzyme (ACE) inhibitors, 1-(N2-substituted L-lysyl-.gamma.-D-glutamyl)octahydro-1H-indole-2-carboxylic acids, was synthesized; various acyl groups were introduced at the .alpha.-amino group of the N-terminal P1 Lys. The effect of the N2-acyl groups on in vitro inhibitory activity and oral antihypertensive effect was examined. All of the synthesized N-acyl tripeptides were found to have in vitro inhibitory activity at an approximately nanomolar level, and showed antihypertensive potency in renal hypertensive rats at a dose of 10 mg/kg, when administered orally. Among them, compounds 7e,g and 8f,i,m showed potent and long-lasting antihypertensive effects compared with enalapril (2a). Their structure-activity relationships are also discussed.This publication has 11 references indexed in Scilit:
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