Alacepril

Description

Alacepril is an angiotensin-converting enzyme (ACE) inhibitor useful in the treatment of essential and renal hypertension. Compared with captopril, alacepril is a weaker ACE inhibitor in vino, yet clinically it has a longer duration of action and appears to be more active due to an added component of norepinephrine antagonism.

Originator

Dainippon (Japan)

Definition

ChEBI: Alacepril is a thioacetate ester and a dipeptide. It has a role as an EC 3.4.15.1 (peptidyl-dipeptidase A) inhibitor.

Manufacturing Process

N-Methylmorpholine (1.03 g) was added to a solution of 1-(D-3-acetylthio-2- methylpropanoyl)-L-proline (2.65 g) in dry tetrahydrofuran (50 ml). The resulting solution was stirred and cooled at -20° to -15°C. Phenyl chloroformate (1.61 g) was added, and after 5 min, a solution of Lphenylalanine t-butyl ester hydrochloride (2.4 g) and N-methylmorpholine (1.03 g) in dry tetrahydrofuran (30 ml) was added. The mixture was stirred at -20° to -15°C for 1 h and then at room temperature overnight.
After removal of insoluble materials by filtration, the filtrate was concentrated under reduced pressure and the residue was dissolved in chloroform.
The chloroform solution was washed successively with 1 N sodium hydroxide, water, 10% citric acid, and water, dried and concentrated under reduced pressure. The residue was chromatographed on silica gel with chloroformmethanol (99:1) to give 4.2 g the 1-(D-3-acetylthio-2-methylpropanoyl)-Lprolyl- L-phenylalanine tert-butyl ester.
1-(D-3-Acetylthio-2-methylpropanoyl)-L-prolyl-L-phenylalanine tert-butyl ester (2.5 g) was dissolved in a mixture of anisole (18 ml) and trifluoroacetic acid (37 ml). The solution was allowed to stand at room temperature for 1 h and then concentrated to dryness under reduced pressure. The residue was crystallized from diethyl ether. The 1-(D-3-acetylthio-2-methylpropanoyl)-Lprolyl- L-phenylalanine was obtained (1.8 g), melting point 155°-156°C (recrystallization from ethanol/n-hexane).

brand name

Cetapril

Therapeutic Function

Antihypertensive