Basic information
- CAS
134523-03-8- Standard SMILES
CC(C)c1c(C(=O)Nc2ccccc2)c(-c2ccccc2)c(-c2ccc(F)cc2)n1CC[C@@H](O)C[C@@H](O)CC(=O)[O-].CC(C)c1c(C(=O)Nc2ccccc2)c(-c2ccccc2)c(-c2ccc(F)cc2)n1CC[C@@H](O)C[C@@H](O)CC(=O)[O-].[Ca+2]- InChIKey
FQCKMBLVYCEXJB-MNSAWQCASA-L- Molecular formula
- C66H68CaF2N4O10
- Average molar mass
- 1,155.3 g/mol
- Monoisotopic mass
- 1,154.4529416
Overview
Atorvastatin calcium is an organic calcium salt composed of calcium cations and atorvastatin anions in a 1:2 ratio. It contains an atorvastatin(1-).
Names & identifiers
- Preferred name
- Atorvastatin Calcium
- IUPAC
- calcium bis((3R,5R)-7-[2-(4-fluorophenyl)-3-phenyl-4-(phenylcarbamoyl)-5-propan-2-ylpyrrol-1-yl]-3,5-dihydroxyheptanoate)
- English name
- Atorvastatin calcium
- Molecular formula
- C33H37CaFN2O5
- Molecular weight
- 600.74
Names & synonyms
ATORVASTATIN CALCIUM134523-03-8TahorAtorvastatin calcium anhydrousCI-981C0GEJ5QCSODTXSID6044303LiprimarAtorvastatin calcium (anhydrous)NSC-758617Calcium (betaR,deltaR)-2-(p-fluorophenyl)-beta,delta-dihydroxy-5-isopropyl-3-phenyl-4-(phenylcarbamoyl)pyrrole-1-heptanoate (1:2)DTXCID4024303
Show more names
Atorvastatin CalciuM TrihydrateAtorvastatin CalciuM APIAtrovastatin calciumATORVASTATIN CAATORVASTATIN CALCIUM SALTAtorvastatin calciuM salt trihydrate[r-(r*, r*)]-7-[2-(4-fluorophenyl)-5-(1-methylethyl)-3-phenyl-4-(phenylaminocarbonyl)-1h-pyrrol-1-yl]-3,5-dihydroxy-heptanoic acid calcium saltAtorvastation CalciuMAtorvastatin Ca HydrateAtorvastatin Calcium RS
CHEBI:50686Atorvastatin calcium salt anhydrousDengue Killcoffeerazzi minerang dutchcoffeeRefChem:916455Atorvastatin, Calcium salt658-046-8686-242-3
Properties
Computed structural properties
- Topological polar surface area
- 229 Ų
- Hydrogen bond donors
- 6
- Hydrogen bond acceptors
- 12
- Rotatable bonds
- 22
- Heavy atoms
- 83
- Formal charge
- 0
- Complexity
- 817
Experimental & physicochemical properties
DrugsPharmaceuticals -> Statins
Human Drugs
FDA approved drugs -> Active ingredient
FDA approved drugs -> Active ingredient
Collision Cross Section231.5 Ų [M+H]+ [CCS Type: TW; Method: calibrated with polyalanine and drug standards]
Physicochemical properties
- Melting point
- 176 · 176-178°C
- storage temp.
- 2 · Keep in dark place,Inert atmosphere,2-8°C
- solubility
- 10 mg/mL · DMSO: ≥10mg/mL
- form
- white powder
- color
- White to Off-White
- BCS Class
- 2 · 2
- Major Application
- pharmaceutical
- InChIKey
- FQCKMBLVYCEXJB-MNSAWQCASA-L
- SMILES
- C(C1=C(N(CC[C@@H](O)C[C@@H](O)CC(=O)O)C(C2C=CC(F)=CC=2)=C1C1C=CC=CC=1)C(C)C)(=O)NC1C=CC=CC=1.[Ca] |&1:6,9,r|
Safety & regulation
Safety information is for reference only and does not replace the supplier’s Safety Data Sheet (SDS), applicable regulations, or professional assessment.
GHS classification
GHS Classification
This chemical does not meet GHS hazard criteria for 2% (3 of 153) of reports.
Warning
H315 (37.3%): Causes skin irritation [Warning Skin corrosion/irritation]
P203, P260, P261, P263, P264, P264+P265, P270, P271, P273, P280, P302+P352, P304+P340, P305+P351+P338, P318, P319, P321, P332+P317, P337+P317, P362+P364, P391, P403+P233, P405, and P501 (click each P-code to see the statement)
Aggregated GHS information provided per 153 reports by companies from 21 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.
This chemical does not meet GHS hazard criteria for 3.4% (1 of 29) of reports.
Hazard information
Hazard Classes and Categories
Skin Irrit. 2 (37.3%)
Eye Irrit. 2B (20.7%)
Toxicology
Exposure Routes
Atorvastatin is rapidly absorbed after oral administration with maximum plasma concentrations achieved in 1 to 2 hours. The absolute bioavailability of atorvastatin (parent drug) is approximately 14% and the systemic availability of HMG-CoA reductase inhibitory activity is approximately 30%. The low systemic bioavailability is due to presystemic clearance by gastrointestinal mucosa and first-pass metabolism in the liver.
Toxicity Summary
Atorvastatin selectively and competitively inhibits the hepatic enzyme HMG-CoA reductase. As HMG-CoA reductase is responsible for converting HMG-CoA to mevalonate in the cholesterol biosynthesis pathway, this results in a subsequent decrease in hepatic cholesterol levels. Decreased hepatic cholesterol levels stimulates upregulation of hepatic LDL-C receptors which increases hepatic uptake of LDL-C and reduces serum LDL-C concentrations.
Chemistry & industry
Pharmacology
Metabolism/Metabolites
Atorvastatin is extensively metabolized to ortho- and parahydroxylated derivatives and various beta-oxidation products. In vitro inhibition of HMG-CoA reductase by ortho- and parahydroxylated metabolites is equivalent to that of atorvastatin. Approximately 70% of circulating inhibitory activity for HMG-CoA reductase is attributed to active metabolites. CYP3A4 is also involved in the metabolism of atorvastatin.
FDA Pharmacological Classification
ATORVASTATIN CALCIUM
HMG-CoA Reductase Inhibitor [EPC]; Hydroxymethylglutaryl-CoA Reductase Inhibitors [MoA]
MeSH Pharmacological Classification
Substances used to lower plasma CHOLESTEROL levels.
Compounds that inhibit HYDROXYMETHYLGLUTARYL COA REDUCTASES. They have been shown to directly lower CHOLESTEROL synthesis.
Uses & manufacturing
Uses
Use (kg) in Switzerland (2009): >1000
May be used as primary prevention in individuals with multiple risk factors for coronary heart disease (CHD) and as secondary prevention in individuals with CHD to reduce the risk of myocardial infarction (MI), stroke, angina, and revascularization procedures. May be used to reduce the risk of cardiovascular events in patients with acute coronary syndrome (ACS). May be used in the treatment of primary hypercholesterolemia and mixed dyslipidemia, homozygous familial hypercholesterolemia, primary dysbetalipoproteinemia, and/or hypertriglyeridemia as an adjunct to dietary therapy to decrease serum total and low-density lipoprotein cholesterol (LDL-C), apolipoprotein B (apoB), and triglyceride concentrations, while increasing high-density lipoprotein cholesterol (HDL-C) levels.
Applications
Atorvastatin calcium (Lipitor®) was launched in Canada, the Netherlands, the UK and the US as an orally-active hypocholesterolemic agent. It was the first pharmaceutical product ever to attain over one billion dollars in sales in its first year. It 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. Lipitor is a liver selective, reversible competitive inhibitor of HMG-CoA reductase, the rate limiting step in cholesterol biosynthesis. Lipitor monotherapy resulted in a reduction of LDL cholesterol by up to 60%. Lipitor is about 2-4 times more potent, on a dosage basis, than Simvastatin. The superior properties of Lipitor can be attributed to its greater uptake and longer duration of action in the liver. In addition to its effects on cholesterol, Lipitor 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.
Related reactions
16 records
Compound notes
Loading…