10186. Zofenopril

Nomenclature

CAS number: 81872-10-8
(4S)-1-[(2S)-3-(Benzoylthio)-2-methyl-1-oxopropyl]-4-(phenylthio)-l-proline; [1(S),4(S)]-1-(3-mercapto-2-methyl-1-oxopropyl)-4-phenyl-thio-l-proline-S-benzoylester.
C22H23NO4S2; mol wt 429.55.
C 61.51%, H 5.40%, N 3.26%, O 14.90%, S 14.93%.

Description and references

Angiotensin-converting enzyme (ACE) inhibitor; de-esterified in vivo to its active sulfhydryl-containing metabolite, zofenoprilat. Prepn: M. A. Ondetti, J. Krapcho, GB 2028327; eidem, US 4316906 (1980, 1982 both to E. R. Squibb & Sons). LC/MS/MS determn in plasma: L. Dal Bo et al., J. Chromatogr. B 749, 287 (2000). Role of sulfhydryl group in improvement of endothelial dysfunction: H. Buikema et al., Br. J. Pharmacol. 130, 1999 (2000); L. Cominacini et al., Am. J. Hypertens. 15, 891 (2002). Clinical comparison with lisinopril of effect on post-infarction survival: C. Borghi, E. Ambrosioni, Am. Heart J. 145, 80 (2003). Review of properties and pharmacokinetics: A. Subissi et al., Cardiovasc. Drug Rev. 17, 115-133 (1999); of clinical efficacy in cardiovascular diseases: C. Borghi et al., Expert Opin. Pharmacother. 5, 1965-1977 (2004).

Chemical structure

Properties

Foamy solid, mp 42-44°. [α]D25 36.5° (c = 1 in methanol).

Derivative

Calcium salt.

Nomenclature

CAS number: 81938-43-4
MEN-8029; SQ-26991; Bifril (Menarini); Zofenil (Menarini).
C44H44CaN2O8S4; mol wt 897.17.
C 58.90%, H 4.94%, Ca 4.47%, N 3.12%, O 14.27%, S 14.30%.

Properties

White crystalline powder, mp >250°. [α]D23 67.6° (c = 1 in methanol/HCl). Partition coefficient (octanol/water): 3.5.

Therapeutic Category

Antihypertensive.

Keywords

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