Synthesis of novel angiotensin converting enzyme inhibitor quinapril and related compounds. A divergence of structure-activity relationships for non-sulfhydryl and sulfhydryl types.

Article Details

Citation

Klutchko S, Blankley CJ, Fleming RW, Hinkley JM, Werner AE, Nordin I, Holmes A, Hoefle ML, Cohen DM, Essenburg AD, et al.

Synthesis of novel angiotensin converting enzyme inhibitor quinapril and related compounds. A divergence of structure-activity relationships for non-sulfhydryl and sulfhydryl types.

J Med Chem. 1986 Oct;29(10):1953-61.

PubMed ID
3020249 [ View in PubMed
]
Abstract

The synthesis and angiotensin converting enzyme (ACE) inhibiting activities of quinapril (CI-906, 22), its active diacid (CI-928, 33), and its dimethoxy analogue (CI-925, 25) are reported. These tetrahydro-3-isoquinolinecarboxylic acid derivatives possess equivalent in vitro potency and in vivo efficacy to enalapril. Sulfhydryl analogues with the same structural variation are also highly potent. In contrast, tetrahydro-1-isoquinolinecarboxylic acid and homologous isoindoline-1-carboxylic acid analogues show a striking divergence in potency between the two types, sulfhydryl analogues being essentially inactive, while non-sulfhydryl analogues are equipotent with the proline prototype. This is the first evidence suggesting that alternate binding modes may exist for the two major structural classes of small molecule ACE inhibitors.

DrugBank Data that Cites this Article

Drug Targets
DrugTargetKindOrganismPharmacological ActionActions
QuinaprilAngiotensin-converting enzymeProteinHumans
Yes
Inhibitor
Details
Binding Properties
DrugTargetPropertyMeasurementpHTemperature (°C)
CaptoprilAngiotensin-converting enzymeIC 50 (nM)13N/AN/ADetails
EnalaprilAngiotensin-converting enzymeIC 50 (nM)140N/AN/ADetails