8539. Simvastatin

Nomenclature

CAS number: 79902-63-9
2,2-Dimethylbutanoic acid (1S,3R,7S,8S,8aR)-1,2,3,7,8,8a-hexahydro-3,7-dimethyl-8-[2-[(2R,4R)-tetrahydro-4-hydroxy-6-oxo-2H-pyran-2-yl]ethyl]-1-naphthalenyl ester; 2,2-dimethylbutyric acid 8-ester with (4R,6R)-6-[2-[(1S,2S,6R,8S,8aR)-1,2,6,7,8,8a-hexahydro-8-hydroxy-2,6-dimethyl-1-naphthyl]ethyl]tetrahydro-4-hydroxy-2H-pyran-2-one; synvinolin; MK-733; Denan (Boehringer, Ing.); Liponorm (Gentili); Lodalès (Sanofi-Synthelabo); Simovil (Merck & Co.); Sinvacor (Merck & Co.); Sivastin (Sigma-Tau); Zocor (Merck & Co.); Zocord (Merck & Co.).
C25H38O5; mol wt 418.57.
C 71.74%, H 9.15%, O 19.11%.

Description and references

HMG-CoA reductase inhibitor; synthetic analog of lovastatin, q.v. Prepn: A. K. Willard et al., EP 33538; W. F. Hoffman et al., US 4444784 (1981, 1984 both to Merck & Co.); W. F. Hoffman et al., J. Med. Chem. 29, 849 (1986). Comprehensive description: D. K. Ellison et al., Anal. Profiles Drug Subs. Excip. 22, 359-388 (1993). HPLC/MS determn in plasma and pharmacokinetics: B. Barrett et al., J. Pharm. Biomed. Anal. 41, 517 (2006). Effect on survival in CHD: Scandinavian Simvastatin Survival Study Group, Lancet 344, 1383 (1994). Clinical trial in primary hypercholesterolemia: L. Ose et al., Clin. Cardiol. 23, 39 (2000); in mixed hyperlipidemia: E. Stein et al., Am. J. Cardiol. 86, 406 (2000). Review of development and clinical experience: J. G. Robinson, Expert Opin. Pharmacother. 8, 2159-2172 (2007); of therapeutic potential in multiple sclerosis: O. Neuhaus, H.-P. Hartung, Expert Rev. Neurother. 7, 547-556 (2007).

Chemical structure

Properties

White to off-white, nonhygroscopic, crystalline powder from n-butyl chloride + hexane, mp 135-138°. Soly (mg/ml): chloroform 610; DMSO 540; methanol 200; ethanol 160; n-hexane 0.15; 0.1M HCl 0.06; polyethylene glycol-400 70; propylene glycol 30; 0.1M NaOH 70; water 0.03. uv max (acetonitrile): 231, 238, 247 nm (A1%1 cm 516, 604, 408). [α]D25 +292° (c = 0.5% in acetonitrile).

Therapeutic Category

Antilipemic.

Keywords

Antilipemic; HMG CoA Reductase Inhibitors; HMG CoA Reductase Inhibitor