8051. Quinapril

Nomenclature

CAS number: 85441-61-8
(3S)-2-[(2S)-2-[[(1S)-1-(Ethoxycarbonyl)-3-phenylpropyl]amino]-1-oxopropyl]-1,2,3,4-tetrahydro-3-isoquinolinecarboxylic acid; (S)-2-[(S)-N-[(S)-1-carboxy-3-phenylpropyl]alanyl]-1,2,3,4-tetrahydro-3-isoquinolinecarboxylic acid 1-ethyl ester.
C25H30N2O5; mol wt 438.52.
C 68.47%, H 6.90%, N 6.39%, O 18.24%.

Description and references

Angiotensin converting enzyme (ACE) inhibitor. Prepn: M. L. Hoefle, S. Klutchko, EP 49605; eidem, US 4344949 (both 1982 to Warner-Lambert); S. Klutchko et al., J. Med. Chem. 29, 1953 (1986) DOI PubMed. Synthesis of purified crystalline form: O. P. Goel, U. Krolls, US 4761479 (1988 to Warner-Lambert). Pharmacology: H. R. Kaplan et al., Fed. Proc. 43, 1326 (1984) PubMed; M. J. Ryan et al., ibid. 1330 PubMed. HPLC determn of quinapril and quinaprilat in plasma and urine: H. Hengy, M. Most, J. Liq. Chromatogr. 11, 517 (1988) DOI. Toxicity data: H. R. Kaplan et al., Angiology 40, 335 (1989) PubMed. Review of pharmacology, pharmacokinetics and clinical experience in congestive heart failure and hypertension: C. R. Culy, B. Jarvis, Drugs 62, 339-385 (2002) DOI PubMed.

Chemical structure

Derivative

Hydrochloride.

Nomenclature

CAS number: 82586-55-8
CI-906; PD-109452-2; Accupril (Parke-Davis); Accupro (Pfizer); Acequin (Recordati); Acuitel (Pfizer); Korec (Sanofi-Aventis); Quinazil (Malesci).
C25H30N2O5.HCl; mol wt 474.98.
C 63.22%, H 6.58%, N 5.90%, O 16.84%, Cl 7.46%.

Properties

Crystals from ethyl acetate-toluene, mp 120-130°. [α]D23 +14.5° (c = 1.2 in ethanol) (Klutchko). Also reported as white crystalline solid from acetonitrile, mp 119-121.5°. [α]D25 +15.4° (c = 2 in methanol) (Goel, Krolls). Freely sol in aq solvents. LD50 in male, female mice, rats (mg/kg): 1739, 1840, 4280, 3541 orally; 504, 523, 158, 107 i.v. (Kaplan, 1989).

Derivative

Diacid.

Nomenclature

CAS number: 82768-85-2
Quinaprilat; CI-928; Accuprin (Pfizer).
C23H26N2O5; mol wt 410.46.
C 67.30%, H 6.38%, N 6.82%, O 19.49%.

Properties

Active metabolite. Hydrate, crystals from methanol-ethyl ether, mp 166-168°. [α]D23 +20.9° (c = 1 in methanol).

Therapeutic Category

Antihypertensive. In treatment of congestive heart failure.

Keywords

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