fluvastatin   

GtoPdb Ligand ID: 2951

Synonyms: Canef® | Lescol®
fluvastatin is an approved drug (FDA (1993))
Compound class: Synthetic organic
Comment: Fluvastatin is a member of the cholesterol-lowering statin family of drugs. The approved drug is a racemic mixture of a 3R, 5S isomer and a 3S, 5R isomer, and this is supported by the INN document which also indicates a racemate. The 3R, 5S isomer (shown here, and in the PubChem link above) is more pharmacologically active [1,4]. The other isomer is represented by CID 1548972. Representations of the stereochemistry of fluvastatin shown on the resources linked to above may vary from the structure shown here. The majority of the references we cite for our biological activity data do not specify whether the racemate or a specific stereoisomer were used in their experiments.
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2D Structure
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Physico-chemical Properties
Hydrogen bond acceptors 4
Hydrogen bond donors 3
Rotatable bonds 8
Topological polar surface area 82.69
Molecular weight 411.18
XLogP 4.51
No. Lipinski's rules broken 0
SMILES / InChI / InChIKey
Canonical SMILES OC(=O)CC(CC(C=Cc1c(c2ccc(cc2)F)c2c(n1C(C)C)cccc2)O)O
Isomeric SMILES OC(=O)C[C@@H](C[C@@H](/C=C/c1c(c2ccc(cc2)F)c2c(n1C(C)C)cccc2)O)O
InChI InChI=1S/C24H26FNO4/c1-15(2)26-21-6-4-3-5-20(21)24(16-7-9-17(25)10-8-16)22(26)12-11-18(27)13-19(28)14-23(29)30/h3-12,15,18-19,27-28H,13-14H2,1-2H3,(H,29,30)/b12-11+/t18-,19-/m1/s1
InChI Key FJLGEFLZQAZZCD-MCBHFWOFSA-N
References
1. Boralli VB, Coelho EB, Sampaio SA, Marques MP, Lanchote VL. (2009)
Enantioselectivity in the pharmacokinetic interaction between fluvastatin and lercanidipine in healthy volunteers.
J Clin Pharmacol, 49 (2): 205-11. [PMID:19033449]
2. Carbonell T, Freire E. (2005)
Binding thermodynamics of statins to HMG-CoA reductase.
Biochemistry, 44 (35): 11741-8. [PMID:16128575]
3. Connolly PJ, Westin CD, Loughney DA, Minor LK. (1993)
HMG-CoA reductase inhibitors: design, synthesis, and biological activity of tetrahydroindazole-substituted 3,5-dihydroxy-6-heptenoic acid sodium salts.
J. Med. Chem., 36 (23): 3674-85. [PMID:8246237]
4. Di Pietro G, Coelho EB, Geleilete TM, Marques MP, Lanchote VL. (2006)
Chiral evaluation of fluvastatin in human plasma by high-performance liquid chromatography electrospray mass spectrometry.
J. Chromatogr. B Analyt. Technol. Biomed. Life Sci., 832 (2): 256-61. [PMID:16480934]
5. Holdgate GA, Ward WH, McTaggart F. (2003)
Molecular mechanism for inhibition of 3-hydroxy-3-methylglutaryl CoA (HMG-CoA) reductase by rosuvastatin.
Biochem. Soc. Trans., 31 (Pt 3): 528-31. [PMID:12773150]
6. Hosoda S, Matsuda D, Tomoda H, Hashimoto M, Aoyama H, Hashimoto Y. (2009)
Application of a 3,3-diphenylpentane skeleton as a multi-template for creation of HMG-CoA reductase inhibitors.
Bioorg. Med. Chem. Lett., 19 (15): 4228-31. [PMID:19502059]
7. Istvan ES, Deisenhofer J. (2001)
Structural mechanism for statin inhibition of HMG-CoA reductase.
Science, 292 (5519): 1160-4. [PMID:11349148]
8. Jendralla H, Granzer E, von Kerekjarto B, Krause R, Schacht U, Baader E, Bartmann W, Beck G, Bergmann A, Kesseler K. (1991)
Synthesis and biological activity of new HMG-CoA reductase inhibitors. 3. Lactones of 6-phenoxy-3,5-dihydroxyhexanoic acids.
J. Med. Chem., 34 (10): 2962-83. [PMID:1656041]
9. McTaggart F, Buckett L, Davidson R, Holdgate G, McCormick A, Schneck D, Smith G, Warwick M. (2001)
Preclinical and clinical pharmacology of Rosuvastatin, a new 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor.
Am. J. Cardiol., 87 (5A): 28B-32B. [PMID:11256847]