Uses
Rosuvastatin Calcium is a competitive inhibitor of HMG-CoA reductase with IC50 of 11 nM.
Definition
ChEBI: Rosuvastatin is a dihydroxy monocarboxylic acid that is (6E)-7-{4-(4-fluorophenyl)-2-[methyl(methylsulfonyl)amino]-6-(propan-2-yl)pyrimidin-5-yl} hept-6-enoic acid carrying two hydroxy substituents at positions 3 and 5 (the 3R,5S-diastereomer). It has a role as an antilipemic drug, an anti-inflammatory agent, a CETP inhibitor, a cardioprotective agent, a xenobiotic and an environmental contaminant. It is a member of pyrimidines, a sulfonamide, a dihydroxy monocarboxylic acid, a statin (synthetic) and a member of monofluorobenzenes. It derives from a hept-6-enoic acid. It is a conjugate acid of a rosuvastatin(1-).
Preparation
Rosuvastatin synthesis: Reduction to the 5-hydroxymethyl derivative proceeds smoothly with diisobutylaluminum hydride (DIBALH) in toluene at -10 °C. The hydroxymethyl group is then converted to the bromo derivative, which upon reaction with triphenylphosphine affords the Wittig reagent. The latter is treated with tert-butyl 2-[(4R,6S)-6-formyl-2,2-dimethyl-1,3-dioxan-4-yl]acetate and provides the protected rosuvastatin ester. Removal of the dioxane protecting group by HCl, ester hydrolysis with NaOH and precipitation with CaCl2 gives rosuvastatin.
Kleemann A; Cardiovascular Drugs. Ullmann's Encyclopedia of Industrial Chemistry 7th ed. (1999-2017). NY, NY: John Wiley & Sons. Online Posting Date: January 15, 2008
Brand name
Crestor (AstraZeneca).
General Description
Rosuvastatin, 7-[4-(4-fluorophenyl)-6-(1-methylethyl)-2-(methyl-methylsulfonyl-amino)-pyrimidin-5-yl]-3,5-dihydroxy-hept-6-enoic acid (Crestor), is oneof the more recently introduced statins in the United States.As with all statins, there is a concern of rhabdomyolysis andas such, the FDA has mandated that a warning about thisside effect, as well as a kidney toxicity warning, be added tothe product label (http://www.fda.gov/CDER/Drug/advisory/crestor_3_2005.htm). This should not come as a surprisebecause of the relationship in the chemical architectureto cerivastatin, which was withdrawn from the market as aresult of its adverse side effects.
Clinical Use
HMG CoA reductase inhibitor:
Hyperlipidaemia
Metabolism
Rosuvastatin undergoes limited metabolism in the liver
mainly by the cytochrome P450 isoenzyme CYP2C9
(approximately 10%).
Approximately 90% of the rosuvastatin dose is excreted
unchanged in the faeces (consisting of absorbed and
non-absorbed active substance) and the remaining part is
excreted in urine.
