Angiotensin converting enzyme inhibitors: spirapril and related compounds
- 1 July 1989
- journal article
- research article
- Published by American Chemical Society (ACS) in Journal of Medicinal Chemistry
- Vol. 32 (7) , 1600-1606
- https://doi.org/10.1021/jm00127a033
Abstract
The synthesis of spirapril (5), spiraprilat (25), their RSS stereoisomers, and their glycyl (18b) and lysyl (36,37) analogues is described. These compounds were evaluated in vivo for inhibition of angiotensin converting enzyme (ACE), and selected compounds were evaluated for in vitro ACE inhibition (spirapril ID50 16 .mu.g/kg; spiraprilat IC50 0.8 nM, ID50 8 .mu.g/kg). In anesthetized rats, iv, esters 5 and 36 are more potent than enalapril and diacids 25 and 37 are more potent than enalaprilat in vitro. In the conscious rats, orally, 5 and enalapril (2) showed potent and sustained activity at doses of 0.03-1 and 0.01-1 mg/kg, respectively. From this work, spirapril was selected for clinical evaluation as an antihypertensive agent.This publication has 21 references indexed in Scilit:
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