Angiotensin converting enzyme inhibitors: spirapril and related compounds.

Article Details

Citation

Smith EM, Swiss GF, Neustadt BR, McNamara P, Gold EH, Sybertz EJ, Baum T

Angiotensin converting enzyme inhibitors: spirapril and related compounds.

J Med Chem. 1989 Jul;32(7):1600-6.

PubMed ID
2544729 [ View in PubMed
]
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 micrograms/kg; spiraprilat IC50 0.8 nM, ID50 8 micrograms/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 0.1-1 mg/kg, respectively. From this work, spirapril was selected for clinical evaluation as an antihypertensive agent.

DrugBank Data that Cites this Article

Binding Properties
DrugTargetPropertyMeasurementpHTemperature (°C)
CaptoprilAngiotensin-converting enzymeIC 50 (nM)13N/AN/ADetails
EnalaprilAngiotensin-converting enzymeIC 50 (nM)1273N/AN/ADetails