Dual angiotensin converting enzyme/thromboxane synthase inhibitors.

Article Details


Ksander GM, Erion M, Yuan AM, Diefenbacher CG, el-Chehabi L, Cote D, Levens N

Dual angiotensin converting enzyme/thromboxane synthase inhibitors.

J Med Chem. 1994 Jun 10;37(12):1823-32.

PubMed ID
8021921 [ View in PubMed

A variety of compounds were prepared to determine whether dual angiotensin converting enzyme (ACE)/thromboxane synthase (TxS) inhibition could be obtained in the same molecule. These compounds would be used to explore the concept that a dual inhibitor would have superior antihypertensive activity in the spontaneous hypertensive rat compared to an ACE inhibitor. Potent in vitro dual ACE and TxS inhibition was obtained in the same molecule with five series of compounds. Potent blood pressure lowering in the SHR was observed after oral administration of 8b and 11. However, a correlation between blood pressure lowering and the A1 pressor response inhibition was not observed. The blood pressure-lowering actions of enalapril were significantly potentiated by concurrent administration of 3, a thromboxane synthase inhibitor. Analysis of the area under the curve for 24 h showed nearly a doubling of the blood pressure-lowering effect.

DrugBank Data that Cites this Article

Binding Properties
DrugTargetPropertyMeasurementpHTemperature (°C)
BenazeprilAngiotensin-converting enzymeIC 50 (nM)2N/AN/ADetails
EnalaprilAngiotensin-converting enzymeIC 50 (nM)2N/AN/ADetails