5516. Lisinopril

Nomenclature

CAS number: 76547-98-3
N2-[(1S)-1-Carboxy-3-phenylpropyl]-l-lysyl-l-proline.
C21H31N3O5; mol wt 405.49.
C 62.20%, H 7.71%, N 10.36%, O 19.73%.

Description and references

Orally active angiotensin-converting enzyme (ACE) inhibitor. Prepn: A. A. Patchett et al., EP 12401; E. E. Harris et al., US 4374829 (1980, 1983 both to Merck & Co.); M. T. Wu et al., J. Pharm. Sci. 74, 352 (1985) DOI PubMed. Comprehensive description: D. P. Ip et al., Anal. Profiles Drug Subs. Excip. 21, 233-276 (1992) DOI. HPLC determn in urine: Y. C. Wong, B. G. Charles, J. Chromatogr. B 673, 306 (1995) DOI; in pharmaceutical formulations: C. A. Beasley et al., J. Pharm. Biomed. Anal. 37, 559 (2005) DOI PubMed. Series of articles in hypertension and congestive heart failure: Am. J. Med. 85, Suppl. 3B, 1-59 (1988). Review of clinical efficacy in myocardial infarction: K. L. Goa et al., Drugs 52, 564-588 (1996) DOI PubMed; in diabetic complications: idem et al., ibid. 53, 1081-1105 (1997) DOI PubMed; in congestive heart failure: K. Simpson, B. Jarvis. ibid. 59, 1149-1167 (2000) DOI PubMed.

Chemical structure

Derivative

Dihydrate.

Nomenclature

CAS number: 83915-83-7
MK-521; Acerbon (AstraZeneca); Alapril (Mediolanum); Carace (Merck & Co.); Coric (BMS); Corprilin (Streuli); Lisitril (Ecosol); Novatec (Merck & Co.); Prinil (Merck & Co.); Prinivil (Merck & Co.); Vivatec (Merck & Co.); Zestril (AstraZeneca).
C21H31N3O5.2H2O; mol wt 441.52.
C 57.13%, H 7.99%, N 9.52%, O 25.37%.

Properties

White to off-white, odorless, crystalline powder. Crystals from methanol:ethyl acetate, mp 159-160°. pKa1 (25°) 2.5; pKa2 4.0; pKa3 6.7; pKa4 10.1. Partition coefficient at room temp (n-octanol/0.1M pH 7 phosphate buffer): 10.2 ±0.5. Approx uv max (0.1N NaOH): 246, 254, 258, 261, 267 nm (A1%1cm 4.0, 4.5, 5.1, 5.1, 3.7); (0.1N HCl): 246, 253, 258, 264, 267 nm (A1%1cm 3.2, 3.9, 4.5, 3.0, 2.8). [α]D25 23.3° (c=1.0 in CH3OH). [α]25405 120° (c = 1 in 0.25M pH 6.4 zinc acetate); [α]25436 96° (c = 1 in 0.25M pH 6.4 zinc acetate). Sol in water; sparingly sol in methanol. Practically insol in ethanol, acetone, acetonitrile, chloroform, DMF.

Therapeutic Category

Antihypertensive.

Therapeutic Category (Veterinary)

Antihypertensive.

Keywords

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