3567. Enalapril

Nomenclature

CAS number: 75847-73-3
N-[(1S)-1-(Ethoxycarbonyl)-3-phenylpropyl]-l-alanyl-l-proline; 1-[N-[(S)-1-carboxy-3-phenylpropyl]-l-alanyl]-l-proline 1′-ethyl ester.
C20H28N2O5; mol wt 376.45.
C 63.81%, H 7.50%, N 7.44%, O 21.25%.

Description and references

Angiotensin-converting enzyme (ACE) inhibitor; de-esterified in vivo to its active diacid metabolite. Prepn: A. A. Patchett et al., EP 12401; E. E. Harris et al., US 4374829 (1980, 1983 both to Merck & Co.); A. A. Patchett et al., Nature 288, 280 (1980) DOI PubMed. Similtaneous determn with enalaprilat in plasma by HPLC-MS/MS: S. Lu et al., J. Pharm. Biomed. Anal. 49, 163 (2009) DOI PubMed. Comprehensive description: D. P. Ip, G. S. Brenner, Anal. Profiles Drug Subs. 16, 207-243 (1987). Review of pharmacology and clinical experience in congestive heart failure: P. A. Todd, K. L. Goa, Drugs 37, 141-161 (1989) DOI PubMed; in hypertension: eidem, ibid. 43, 346-381 (1992) DOI PubMed. Review of clinical pharmacokinetics: R. J. MacFadyen et al., Clin. Pharmacokinet. 25, 274-282 (1993) DOI PubMed. Review of combination with hydrochlorothiazide: P. L. Malini, Adv. Ther. 10, 253-262 (1993); with lercanidipine: V. Barrios et al., Vasc. Health Risk Manag. 4, 847-853 (2008) PubMed.

Chemical structure

Derivative

Maleate.

Nomenclature

CAS number: 76095-16-4
MK-421; Amprace (Merck & Co.); Cardiovet (Intervet); Enacard (Merial); Enapren (Merck & Co.); Glioten (Armstrong); Hipoartel (Ipsen); Innovace (Merck & Co.); Naprilene (Sigma-Tau); Pres (Boehringer, Ing.); Renitec (Merck & Co.); Reniten (Merck & Co.); Renivace (Merck & Co.); Vasotec (Merck & Co.); Xanef (Merck & Co.).
C20H28N2O5.C4H4O4; mol wt 492.52.
C 58.53%, H 6.55%, N 5.69%, O 29.24%.

Properties

White to off-white crystalline powder, mp 143-144.5°. Soly (g/ml): water 0.025; alcohol 0.08; methanol 0.20. [α]D25 -42.2° (c = 1 in methanol). pH (1% water) 2.6. pKa1 3.0; pKa2 (25°) 5.4.

Derivative

Diacid dihydrate.

Nomenclature

CAS number: 84680-54-6; 76420-72-9 (anhydrous)
Enalaprilat; enalaprilic acid; MK-422; Vasotec I.V (Merck & Co.).
C18H24N2O5.2H2O; mol wt 384.42.
C 56.24%, H 7.34%, N 7.29%, O 29.13%.

Properties

Needles from H2O, mp 148-151°. [α]D -67.0° (0.1M HCl). Sparingly sol in methanol; slightly sol in water.

Therapeutic Category

Antihypertensive.

Therapeutic Category (Veterinary)

In treatment of heart failure in dogs.

Keywords

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