Tmic
You are using an unsupported browser. Please upgrade your browser to a newer version to get the best experience on Database of hazardous chemicals.
Record Information
Version1.0
Creation Date2014-10-14 21:18:31 UTC
Update Date2016-10-28 10:03:33 UTC
Accession NumberCHEM003934
Identification
Common NameAtorvastatin
ClassSmall Molecule
DescriptionAtorvastatin (Lipitor) is a member of the drug class known as statins. It is used for lowering cholesterol. Atorvastatin is a competitive inhibitor of hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase, the rate-determining enzyme in cholesterol biosynthesis via the mevalonate pathway. HMG-CoA reductase catalyzes the conversion of HMG-CoA to mevalonate. Atorvastatin acts primarily in the liver. Decreased hepatic cholesterol levels increases hepatic uptake of cholesterol and reduces plasma cholesterol levels.
Contaminant Sources
  • FooDB Chemicals
  • STOFF IDENT Compounds
  • Suspected Compounds
  • Suspected Compounds - Waste Water
  • T3DB toxins
  • ToxCast & Tox21 Chemicals
Contaminant Type
  • Anticholesteremic Agent
  • Drug
  • Hydroxymethylglutaryl-CoA Reductase Inhibitor
  • Metabolite
  • Synthetic Compound
Chemical Structure
Thumb
SynonymsNot Available
Chemical FormulaC33H34FN2O5
Average Molecular Mass557.632 g/mol
Monoisotopic Mass557.245 g/mol
CAS Registry Number134523-00-5
IUPAC Name7-[2-(4-fluorophenyl)-3-phenyl-4-(phenylcarbamoyl)-5-(propan-2-yl)-1H-pyrrol-1-yl]-3,5-dihydroxyheptanoate
Traditional Name7-[2-(4-fluorophenyl)-5-isopropyl-3-phenyl-4-(phenylcarbamoyl)pyrrol-1-yl]-3,5-dihydroxyheptanoate
SMILESCC(C)C1=C(C(=O)NC2=CC=CC=C2)C(=C(N1CCC(O)CC(O)CC([O-])=O)C1=CC=C(F)C=C1)C1=CC=CC=C1
InChI IdentifierInChI=1S/C33H35FN2O5/c1-21(2)31-30(33(41)35-25-11-7-4-8-12-25)29(22-9-5-3-6-10-22)32(23-13-15-24(34)16-14-23)36(31)18-17-26(37)19-27(38)20-28(39)40/h3-16,21,26-27,37-38H,17-20H2,1-2H3,(H,35,41)(H,39,40)/p-1
InChI KeyXUKUURHRXDUEBC-UHFFFAOYSA-M
Chemical Taxonomy
Description belongs to the class of organic compounds known as diphenylpyrroles. These are aromatic heterocyclic compounds with a structure based on a pyrrole ring linked to exactly two phenyl groups.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassPyrroles
Sub ClassSubstituted pyrroles
Direct ParentDiphenylpyrroles
Alternative Parents
Substituents
  • 2,3-diphenylpyrrole
  • Aromatic anilide
  • Medium-chain hydroxy acid
  • Pyrrole-3-carboxamide
  • Pyrrole-3-carboxylic acid or derivatives
  • Medium-chain fatty acid
  • Beta-hydroxy acid
  • Fluorobenzene
  • Halobenzene
  • Hydroxy fatty acid
  • Halogenated fatty acid
  • Heterocyclic fatty acid
  • Benzenoid
  • Fatty acid
  • Hydroxy acid
  • Fatty acyl
  • Monocyclic benzene moiety
  • Aryl halide
  • Aryl fluoride
  • Heteroaromatic compound
  • Vinylogous amide
  • Carboxamide group
  • Secondary alcohol
  • Secondary carboxylic acid amide
  • Monocarboxylic acid or derivatives
  • Carboxylic acid derivative
  • Carboxylic acid
  • Azacycle
  • Organonitrogen compound
  • Organofluoride
  • Alcohol
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organohalogen compound
  • Carbonyl group
  • Organic oxide
  • Organopnictogen compound
  • Organic oxygen compound
  • Organic nitrogen compound
  • Organic anion
  • Aromatic heteromonocyclic compound
Molecular FrameworkAromatic heteromonocyclic compounds
External DescriptorsNot Available
Biological Properties
StatusDetected and Not Quantified
OriginEndogenous
Cellular Locations
  • Membrane
Biofluid LocationsNot Available
Tissue Locations
  • Liver
  • Platelet
PathwaysNot Available
ApplicationsNot Available
Biological RolesNot Available
Chemical RolesNot Available
Physical Properties
StateSolid
AppearanceNot Available
Experimental Properties
PropertyValue
Melting Point159.2-160.7 °C
Boiling PointNot Available
SolubilitySodium salt soluble in water, 20.4 ug/mL (pH 2.1), 1.23 mg/mL (pH 6.0)
Predicted Properties
PropertyValueSource
Water Solubility0.00049 g/LALOGPS
logP4.41ALOGPS
logP5.39ChemAxon
logS-6.1ALOGPS
pKa (Strongest Acidic)4.33ChemAxon
pKa (Strongest Basic)-2.7ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count3ChemAxon
Polar Surface Area114.62 ŲChemAxon
Rotatable Bond Count12ChemAxon
Refractivity169.04 m³·mol⁻¹ChemAxon
Polarizability59.7 ųChemAxon
Number of Rings4ChemAxon
Bioavailability0ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash Key
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-0aor-0000090000-401e9c7a2f170820f729View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-014j-0000090000-647b0fa490907c33201cView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-000j-4200790000-a372fe1f0093d1e98cd3View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-0a4i-2100090000-fe1fdeff5a26f7f83882View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0a4i-8400090000-7dd2f7f373fb6fd5de88View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0a4i-9500120000-34427c424cc44ee99074View in MoNA
Toxicity Profile
Route of ExposureAtorvastatin 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.
Mechanism of ToxicityAtorvastatin 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.
MetabolismAtorvastatin 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.
Toxicity ValuesGenerally well-tolerated. Side effects may include myalgia, constipation, asthenia, abdominal pain, and nausea. Other possible side effects include myotoxicity (myopathy, myositis, rhabdomyolysis) and hepatotoxicity. To avoid toxicity in Asian patients, lower doses should be considered.
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesMay 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.
Minimum Risk LevelNot Available
Health EffectsNot Available
SymptomsNot Available
TreatmentNot Available
Concentrations
Not Available
DrugBank IDNot Available
HMDB IDNot Available
FooDB IDNot Available
Phenol Explorer IDNot Available
KNApSAcK IDNot Available
BiGG IDNot Available
BioCyc IDNot Available
METLIN IDNot Available
PDB IDNot Available
Wikipedia LinkAtorvastatin
Chemspider IDNot Available
ChEBI IDNot Available
PubChem Compound ID4636594
Kegg Compound IDNot Available
YMDB IDNot Available
ECMDB IDNot Available
References
Synthesis Reference

Zlatko Pflaum, “Process for the preparation of amorphous atorvastatin.” U.S. Patent US20020183527, issued December 05, 2002.

MSDSNot Available
General ReferencesNot Available