200. Alacepril

Nomenclature

CAS number: 74258-86-9
1-[(2S)-3-(Acetylthio)-2-methyl-1-oxopropyl]-l-prolyl-l-phenylalanine; 1-(d-3-acetylthio-2-methylpropanoyl)-l-prolyl-l-phenylalanine; N-[1-[(S)-3-mercapto-2-methylpropionyl]-l-prolyl]-3-phenyl-l-alanine acetate (ester); DU-1219; Cetapril (Dainippon).
C20H26N2O5S; mol wt 406.50.
C 59.09%, H 6.45%, N 6.89%, O 19.68%, S 7.89%.

Description and references

Angiotensin-converting enzyme (ACE) inhibitor. Prepn: T. Sawayama et al., JP Kokai 80 9058; eidem, US 4248883 (1980, 1981 both to Dainippon Pharm.). Pharmacology in animals: K. Takeyama et al., Arzneim.-Forsch. 35, 1502 (1985); eidem, ibid. 1507. Series of articles on pharmacology, metabolism, enzyme inhibiting activity: ibid. 36, 47-83 (1986). Metabolism to captopril, q.v.: K. Matsumoto et al., ibid. 40. HPLC determn of metabolites in plasma and urine: K. Hayashi et al., J. Chromatogr. 338, 161 (1985). Pharmacokinetics in humans: K. Onoyama et al., Clin. Pharmacol. Ther. 38, 462 (1985). Preclinical evaluation in essential hypertension: K. Mizuno et al., Res. Commun. Chem. Pathol. Pharmacol. 49, 175 (1985); H. Shionoiri et al., Curr. Ther. Res. 38, 537 (1985). Series of articles on toxicology: M. Iida et al., Yakuri to Chiryo 13, 7033-7121 (1985), C.A. 104, 21888h-21890c; 105, 396v (1986).

Chemical structure

Properties

Crystals from ethanol/n-hexane, mp 155-156°. [α]D25 81.3° (c = 1.02 in ethanol). LD50 in rats, mice (mg/kg): >5000, >5000 orally; >3000, >3000 s.c.; ≈2000, ≈3000 i.p. (Iida, pp 7033-40).

Therapeutic Category

Antihypertensive.

Keywords

ACE-Inhibitor; Antihypertensive; N-Carboxyalkyl (peptide/lactam) Derivatives