2272. Cilastatin

Nomenclature

CAS number: 82009-34-5
(2Z)-7-[[(2R)-2-Amino-2-carboxyethyl]thio]-2-[[[(1S)-2,2-dimethylcyclopropyl]carbonyl]amino]-2-heptenoic acid; MK-791.
C16H26N2O5S; mol wt 358.45.
C 53.61%, H 7.31%, N 7.82%, O 22.32%, S 8.95%.

Description and references

Reversible dehydropeptidase I inhibitor; prevents renal metabolism of penem and carbapenem antibiotics. Prepn: D. W. Graham et al., EP 48301(1982 to Merck & Co.); and activity: idem et al., J. Med. Chem. 30, 1074 (1987). Combination with thienamycins: H. Kropp et al., EP 48025; F. M. Kahan, H. Kropp, US 4539208 (1982, 1985 both to Merck & Co.). HPLC determn in serum: C. M. Myers, J. L. Blumer, Antimicrob. Agents Chemother 26, 78 (1984). Effect on imipenem pharmacokinetics: S. R. Norrby et al., ibid. 23, 300 (1983); on intrathecal penetration of imipenem: A. W. Chow et al., ibid. 23, 634 (1983). Series of articles on pharmacokinetics, tolerance, and efficacy of combination with imipenem: J. Antimicrob. Chemother. 12, Suppl. D, 1-155 (1983); Infection 14, Suppl. 2, S111-S180 (1986). Review of clinical experience in serious infections: J. A. Balfour et al., Drugs 51, 99-136 (1996); of nephroprotective effect with cyclosporin: A. Tejedor et al., Curr. Med. Res. Opin. 23, 505-513 (2007).

Chemical structure

Properties

Amorphous solid. [α]D25 +17.6° (c = 0.5 in methanol). [α]D25 +14.2° (c = 0.5 in 0.1N HCl).

Derivative

Sodium salt.

Nomenclature

CAS number: 81129-83-1
Cilastatin sodium.
C16H25N2NaO5S; mol wt 380.43.
C 50.51%, H 6.62%, N 7.36%, Na 6.04%, O 21.03%, S 8.43%.

Properties

Off-white to yellowish-white hygroscopic, amorphous solid. pKa1 2.0; pKa2 4.4; pKa3 9.2. Very sol in water, methanol.

Derivative

Mixture of sodium salt with imipenem see Imipenem.

Therapeutic Category

Antibacterial adjunct (dipeptidase inhibitor).

Keywords

Antibacterial Adjuncts; Renal Dipeptidase Inhibitors