Quick Search
Atorvastatın Calcıum, sold under the brand name Lipitor among others, is a statin medication used to prevent cardiovascular disease in those at high risk and to treat abnormal lipid levels.
For the prevention of cardiovascular disease, statins are a first-line treatment in reducing cholesterol.
Atorvastatın Calcıum is taken by mouth.
CAS: 134523-03-8
MF: C33H37CaFN2O5
MW: 600.74
EINECS: 200-659-6
Synonyms
ATORVASTATIN CALCIUM SALT;ATORVASTATIN CALCIUM;ATORVASTATIN CA;[r-(r*, r*)]-7-[2-(4-fluorophenyl)-5-(1-methylethyl)-3-phenyl-4-(phenylaminocarbonyl)-1h-pyrrol-1-yl]-3,5-dihydroxy-heptanoic acid calcium salt;(3R,5R)-7-(2-(4-FLUOROPHENYL)-5-ISOPROPYL-3-PHENYL-4-(PHENYLCARBAMOYL)-1H-PYRROL-1-YL)-3,5-DIHYDROXYHEPTANOIC ACID CALCIUM;(3R,5R)-7-(2-(4-fluorophenyl)-5-isopropyl-3-;(R,dR)-2-(4-Fluorophenyl)-,d-dihydroxy-5-(1-methylethyl)-3-phenyl-4-[(phenylamino)carbonyl]-1H-pyrrole-1-heptanoic Acid Calcium;3S,5S-Atorvastatin Calcium
An organic calcium salt composed of calcium cations and Atorvastatın Calcıum anions in a 1:2 ratio.
Common side effects may include diarrhea, heartburn, nausea, muscle pain (typically mild and dose-dependent) and, less frequently, joint pain.
Muscle symptoms often occur during the first year and are commonly influenced by pre-existing health issues and the nocebo effect.
Most patients can continue therapy with dose adjustment or statin switching.
Rare (<0.1%) but serious side effects may include rhabdomyolysis (severe muscle disorder), liver problems and diabetes.
Use during pregnancy may harm the fetus.
Like all statins, atorvastatin works by inhibiting HMG-CoA reductase, an enzyme found in the liver that plays a role in producing cholesterol.
Atorvastatın Calcium was patented in 1986, and approved for medical use in the United States in 1996.
Atorvastatın Calcium is on the World Health Organization's List of Essential Medicines.
Atorvastatın Calcıum is available as a generic medication.
In 2022, Atorvastatın Calcıum was the most commonly prescribed medication in the United States, with more than 109 million prescriptions filled for over 27 million people.
In Australia, Atorvastatın Calcium was one of the top ten most prescribed medications between 2017 and 2023.
Atorvastatın Calcium is a statin-class medication used mainly for lowering the lipid as well as preventing the event associated with cardiovascular disease.
Being similar to other kinds of statins, atorvastatin take effects by inhibiting HMG-CoA reductase, an enzyme found in liver tissue that plays a key role in production of cholesterol in the body.
Atorvastatın Calcium acts primarily in the liver.
Decreased hepatic cholesterol levels further increases hepatic uptake of cholesterol and reduces plasma cholesterol levels.
Lipitor, since 1996, has become the world's best-selling medication to that point, with more than US$125 billion in sales over approximately 14.5 years.
As of 2016, in the UK, atorvastatin costs about £2 per month.
Lipitor was launched in Canada, the Netherlands, the UK and the US as an orally-active hypocholesterolemic agent.
Atorvastatın Calcium was the first pharmaceutical product ever to attain over one billion dollars in sales in its first year.
Atorvastatın Calcium can be synthesized by a number of routes but the most efficient involves the Paal-Knorr reaction of an acetonide protected dihydroxy amino ester and a diaryl phenylacetamide diketone.
Atorvastatın Calcium is a liver selective, reversible competitive inhibitor of HMG-CoA reductase, the rate limiting step in cholesterol biosynthesis.
Atorvastatın Calcium monotherapy resulted in a reduction of LDL cholesterol by up to 60%.
Atorvastatın Calcium is about 2-4 times more potent, on a dosage basis, than Simvastatin.
The superior properties of Atorvastatın Calcium can be attributed to its greater uptake and longer duration of action in the liver.
In addition to its effects on cholesterol, Atorvastatın Calcium is also effective in lowering triglycerides.
While the mechanism is not clear, two theories proposed are: a) the decrease in cholesterol causes a concomitant increase in hepatic LDL-receptor activity (mostly B and E type) which results in a decrease in triglycerides through an increase in binding of triglycerides to VLDL and LDL, and b) the decreased level of cholesterol impairs VLDL transport of triglycerides.
Atorvastatin calcium Chemical Properties
Melting point: 176-178°C
Storage temp.: Keep in dark place,Inert atmosphere,2-8°C
Solubility: DMSO: ≥10mg/mL
Form: white powder
Color: White to Off-White
BCS Class: 2
InChIKey: FQCKMBLVYCEXJB-MNSAWQCASA-L
CAS DataBase Reference: 134523-03-8(CAS DataBase Reference)
EPA Substance Registry System: Atorvastatın Calcium (134523-03-8)
Uses
Atorvastatın Calcium is a compound used as standard in the method development and validation for simultaneous determination of Atorvastatin calcium and Ezetimibe (E975000) in tablets using UV spectrophotometric, HPLC and HPTLC methods.
A selective, competitive HMG-CoA reductase inhibitor.
The only drug in its class specfically indicated for lowering both elevated LDL-cholesterol and triglycerides in patients with hypercholesterolemia
The primary uses of atorvastatin is for the treatment of dyslipidemia and the prevention of cardiovascular disease.
A selective, competitive HMG-CoA reductase inhibitor.
Atorvastatın Calcium is the only drug in its class specfically indicated for lowering both elevated LDL-cholesterol and triglycerides in patients with hypercholesterolemia.
Manufacturing Process
285 ml 2.2 M n-butyl lithium in hexane was added dropwise to 92 ml diisopropylamine at -50-60°C under nitrogen.
The well stirred solutions warmed to about -20°C, then Atorvastatın Calcium was cannulated into a suspension of 99 g of S(+)-2-acetoxy-1,1,2-triphenylethanol in 500 ml absolute tetrahydrophuran (THF) at -70°C and the reaction mixture was allowed to warm to -10°C for 2 hours.
A suspension of MgBr2 was made from 564 ml (0.63 mol) of bromine and 15.3 g of magnesium (0.63 mol) in 500 ml THF cooled to -78°C.
The enolate solution was cannulated into this suspension within 30 min and was stirred for 60 min at -78°C. 150 g 5-(4-fluorophenyl)-2-(1-methylethyl)-1-(3- oxopropyl)-N,4-diphenyl-1H-pyrrole-3-carboxamide in 800 ml absolute THF was added dropwise over 30 min, stirred 90 min at -78°C, then was added 200 ml acetic acid, this is removed to a cool bath, 500 ml of H2O was added and the mixture concentrate in vacuo at 40-50°C.
After adding of 500 ml of 1:1 EtOAc/heptane the mixture was filtered.
The filtrate was washed extensively with 0.5 N HCl, then several times with H2O and finally EtOAc/heptane (3:1) and cooled with dry ice to -20°C.
The light brown crystalline product was dried in vacuum oven at 40°C.
The yield was 194 g. 112 g of the same product was produced by evaporation of mother liquor after recrystallization and chromatographic purification on a silicagel.
162 g of this substance was suspended in methanol/THF (5:3) and was stirred with 11.7 g of sodium methoxide until everything was dissolved and kept in the freezer overnight.
Later it was quenched with AcOH concentrated in vacuo, was added to 500 ml H2O and extracted twice with EtOAc (300 ml).
The combined extracts was washed with saturated NaHCO3 brine and dried over anhydrous MgSO4, purified on silica-gel and gave 86.1 g of white crystals m.p. 125-126°C, αD 20=4.23° (1.17 M, CH3OH).
81 g of the last product in 500 ml absolute THF was added as quickly as possible to the mixture of 77 ml THF at diisopropylamine, 200 ml 2.2 M of nbutyl lithium and 62 ml of t-butylacetate in 200 ml THF -40-42°C under nitrogen. Stirring was continued for 4 hours at -70°C.
The reaction mixture was concentrated in vacuo, the residue was taken up in EtOAc, washed with water, then saturated NH4Cl, NaHCO3 (saturated), dried over anhydrous MgSO4, filtred and the solvent evaporated.
The organic phase was dried and concentrated in vacuo to yield 73 g crude product, that was dissolved in 500 ml absolute THF, 120 ml triehtylborane and 0.7 g t-butylcarboxylic acid, 70 ml methanol and 4.5 g sodium borohydride was added.
The mixture was stirred at -78°C under a dry atmosphere for 6 hours, poured slowly into 4:1:1 mixture of ice/30%H2O2/H2O and stirred overnight.
CHCl3 (400 ml) was added and organic layer washed extensively with H2O until no peroxide could be found, was dried over MgSO4, filtered and was treated by chromatography on silica gel to yield 51 g.
The product was dissolved in THF/methanol and saponificated with NaOH and, concentrated to remove organic solvents at room temperature, added 100 ml H2O, and extracted with Et2O twice.
Organic layer was thoroughly dried and Atorvastatın Calcium was left at room temperature for the next 10 days, then concentrated.
Chromatography on silica gel yielded 13.2 g racemate of lactone - trans-(+/- )-5-(4-fluorophenyl)-2-(1-methylethyl)-N,4-di-diphenyl-1-[2-(tetrahydro-4- hydroxy-6-oxo-2H-pyran-2-yl)ethyl]-1H-pyrrole-3-carboxamide.
This racemate was divided by chiral synthesis which was made analogously the method in US Pat. No. 4,581,893.
Then each isomer was saponificated with NaOH and purificated by HPLC.
The calcium salt corresponding acid was prepared by reaction with 1 eq. of CaCl2·2H2O in water.
