74258-86-9

Basic information

• Product Name: Alacepril
• Synonyms: (s)-l-phenylalanin;1-(d-3-acetylthio-2-methylpropanoyl)-l-prolyl-l-phenylalanine;cetapril;du1219;ALACEPRIL;L-Phenylalanine, 1-[(2S)-3-(acetylthio)-2-methyl-1-oxopropyl]-L-prolyl-;L-Phenylalanine, N-[1-[3-(acetylthio)-2-methyl-1-oxopropyl]-L-prolyl]-, (S)-;2-[[1-(3-Acetylsulfanyl-2-methylpropanoyl)pyrrolidine-2-carbonyl]amino]-3-phenylpropanoic acid
• CAS NO: 74258-86-9
• Molecular Formula: C₂₀H₂₆N₂O₅S
• Molecular Weight: 406.5
• Product Categories: Active Pharmaceutical Ingredients
• Mol File: 74258-86-9.mol
• Article Data: 3

Chemical Properties

• Melting Point: 155-156°
• Boiling Point: 679.1 °C at 760 mmHg
• Flash Point: 364.5 °C
• Appearance: /
• Density: 1.281 g/cm³
• Vapor Pressure: 2.26E-19mmHg at 25°C
• Refractive Index: 1.581
• Storage Temp.: 2-8°C
• CAS DataBase Reference: Alacepril(CAS DataBase Reference)
• NIST Chemistry Reference: Alacepril(74258-86-9)
• EPA Substance Registry System: Alacepril(74258-86-9)

Safety Data

• Hazardous Substances Data: 74258-86-9(Hazardous Substances Data)

Usage

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.

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

InChI:InChI=1/C20H26N2O5S/c1-13(12-28-14(2)23)19(25)22-10-6-9-17(22)18(24)21-16(20(26)27)11-15-7-4-3-5-8-15/h3-5,7-8,13,16-17H,6,9-12H2,1-2H3,(H,21,24)(H,26,27)/t13-,16+,17+/m1/s1

Upstream product

• 74345-73-6 (2R,S)-3-Acetylthio-2-methylpropanoyl chloride 
• 13589-02-1 L-prolyl-L-phenylalanine 
• 13200-83-4 (2S)-1-formylpyrrolidine-2-carboxylic acid 
• 64805-64-7 3-(Acetylthio)-2-methylpropionyl chloride 
• 147-85-3 L-proline 
• 129398-84-1 (S)-methyl 2-((S)-1-formylpyrrolidine-2-carbonylamino)-3-phenylpropanoate 
• 7524-50-7 methyl (2S)-2-amino-3-phenylpropanoate hydrochloride 
• 74258-85-8 1-[(2S)-3-(acetylthio)-2-methyl-1-oxopropyl]-L-prolyl-L-phenylalanine tert-butyl ester 

Downstream Products

• 801293-47-0 1-[(2S)-3-(acetylthio)-2-methyl-1-oxopropyl]-L-prolyl-L-phenylalanine 3-bromomethyl phenyl ester 
• 74259-08-8 1-((S)-3-mercapto-2-methylpropanoyl)-L-prolyl-L-phenylalanine 

Relevant articles and documents

CAPTOPRIL DERIVATIVES

Captopril nitroderivatives having improved pharmacological activity and enhanced tolerability are described. They can be employed for the treatment or prophylaxis of cardiovascular, inflammatory and renal diseases.

1-(3-Mercapto-2-methylpropanoyl)prolyl amino acid derivatives and salts thereof, processes for their preparation, and pharmaceutical compositions containing such compounds

1-(3-Mercapto-2-methylpropanoyl)prolyl amino acid derivatives of the formula STR1 wherein R represents a hydrogen atom, a lower alkyl group, a phenyl-lower alkyl group or a substituted phenyl-lower alkyl group, R1 represents a hydrogen atom, R