Ezetimibe (CHEM017899)

IdentificationTaxonomyBiological PropertiesPhysical PropertiesToxicity ProfileSpectraConcentrationsLinksReferencesXML
Record Information
Version1.0
Creation Date2016-05-22 04:43:29 UTC
Update Date2016-11-09 01:15:41 UTC
Accession NumberCHEM017899
Identification
Common NameEzetimibe
ClassSmall Molecule
DescriptionEzetimibe is a lipid-lowering compound that inhibits intestinal cholesterol and phytosterol absorption. The discovery and research of this drug began in the early 1990s, after the intravenous administration of radiolabelled ezetimibe in rats revealed that it was being localized within enterocytes of the intestinal villi - this prompted studies investigating the effect of ezetimibe on intestinal cholesterol absorption. Ezetimibe is used as an adjunctive therapy to a healthy diet to lower cholesterol levels in primary hyperlipidemia, mixed hyperlipidemia, homozygous familial hypercholesterolemia (HoFH), and homozygous sitosterolemia (phytosterolemia). Unlike other classes of cholesterol-reducing compounds including statins and bile acid sequestrants, ezetimibe has a distinct mechanism of action involving the sterol transporter Niemann-Pick C1-Like 1 (NPC1L1), and is unique in that it does not affect the absorption of fat-soluble nutrients such as fat-soluble vitamins, triglycerides, or bile acids. In genetically NPC1L1-deficient mice, a 70% reduction in intestinal cholesterol absorption was seen, and these mice were insensitive to ezetimibe treatment - it was determined based on these findings that NPC1L1 plays an essential role in promoting intestinal cholesterol uptake via an ezetimibe-sensitive pathway. By interfering with the intestinal uptake of cholesterol and phytosterols, ezetimibe reduces the delivery of intestinal cholesterol to the liver.
Contaminant Sources
  • HMDB Contaminants - Urine
  • STOFF IDENT Compounds
  • ToxCast & Tox21 Chemicals
Contaminant TypeNot Available
Chemical Structure
Thumb
MOLSDFPDBSMILESInChI
Synonyms
ValueSource
EzedocChEBI
EzetimibaChEBI
EzetimibumChEBI
EzetrolChEBI
ZetiaChEBI
(1-(4-Fluorophenyl)-(3R)-(3-(4-fluorophenyl)-(3S)-hydroxypropyl)-(4S)-(4-hydroxyphenyl)-2-azetidinone)HMDB
EzetimibHMDB
Chemical FormulaC24H21F2NO3
Average Molecular Mass409.425 g/mol
Monoisotopic Mass409.149 g/mol
CAS Registry Number163222-33-1
IUPAC Name(3R,4S)-1-(4-fluorophenyl)-3-[(3S)-3-(4-fluorophenyl)-3-hydroxypropyl]-4-(4-hydroxyphenyl)azetidin-2-one
Traditional Nameezetimibe
SMILESO[C@@H](CC[C@@H]1[C@H](N(C1=O)C1=CC=C(F)C=C1)C1=CC=C(O)C=C1)C1=CC=C(F)C=C1
InChI IdentifierInChI=1S/C24H21F2NO3/c25-17-5-1-15(2-6-17)22(29)14-13-21-23(16-3-11-20(28)12-4-16)27(24(21)30)19-9-7-18(26)8-10-19/h1-12,21-23,28-29H,13-14H2/t21-,22+,23-/m1/s1
InChI KeyOLNTVTPDXPETLC-XPWALMASSA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as monobactams. Monobactams are compounds comprising beta-lactam ring is alone and not fused to another ring.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassLactams
Sub ClassBeta lactams
Direct ParentMonobactams
Alternative Parents
Substituents
  • Monobactam
  • 1-phenylazetidine
  • 2-phenylazetidine
  • 1-hydroxy-2-unsubstituted benzenoid
  • Fluorobenzene
  • Halobenzene
  • Phenol
  • Aryl fluoride
  • Aryl halide
  • Monocyclic benzene moiety
  • Benzenoid
  • Tertiary carboxylic acid amide
  • Azetidine
  • Carboxamide group
  • Secondary alcohol
  • Azacycle
  • Carboxylic acid derivative
  • Organonitrogen compound
  • Organofluoride
  • Organohalogen compound
  • Hydrocarbon derivative
  • Organic oxide
  • Carbonyl group
  • Organopnictogen compound
  • Alcohol
  • Organic oxygen compound
  • Organooxygen compound
  • Aromatic alcohol
  • Organic nitrogen compound
  • Aromatic heteromonocyclic compound
Molecular FrameworkAromatic heteromonocyclic compounds
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginNot Available
Cellular LocationsNot Available
Biofluid LocationsNot Available
Tissue LocationsNot Available
PathwaysNot Available
ApplicationsNot Available
Biological RolesNot Available
Chemical RolesNot Available
Physical Properties
StateNot Available
AppearanceNot Available
Experimental Properties
PropertyValue
Melting PointNot Available
Boiling PointNot Available
SolubilityNot Available
Predicted Properties
PropertyValueSource
Water Solubility0.0085 g/LALOGPS
logP4.14ALOGPS
logP4.56ChemAxon
logS-4.7ALOGPS
pKa (Strongest Acidic)9.48ChemAxon
pKa (Strongest Basic)-3ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area60.77 ŲChemAxon
Rotatable Bond Count6ChemAxon
Refractivity108.86 m³·mol⁻¹ChemAxon
Polarizability41.64 ųChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash KeyView
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-05c6-2945000000-8a37190570bab21d1d02Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (2 TMS) - 70eV, Positivesplash10-0002-1903310000-633b71d71a358012cf6aSpectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, PositiveNot AvailableSpectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, PositiveNot AvailableSpectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-qTof , Positivesplash10-0a6r-0692700000-11f020dfbb889ac85e4eSpectrum
LC-MS/MSLC-MS/MS Spectrum - , positivesplash10-000i-1910000000-5b24d4adc8cd3de959fcSpectrum
LC-MS/MSLC-MS/MS Spectrum - 35V, Positivesplash10-001r-0901000000-e8fcc0996c187fba951cSpectrum
LC-MS/MSLC-MS/MS Spectrum - 35V, Negativesplash10-00di-0090000000-cd400e80926d97660b98Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-01ox-0149600000-6c8e6056b5e23340ee0eSpectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-02i6-1794200000-9502e8a01ff6f30b9fc1Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-072a-2950000000-eed640a1fd606e7a63b4Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-0a4i-0122900000-b96ba99bfc7c99941d6bSpectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0006-1921100000-e17ecfb5ab2d745ce445Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-01pa-4941000000-a0f53760eaaecdb35c3dSpectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-03di-0103900000-2a34f2e670639f066936Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-01ox-0459200000-423316cd7c679c84feccSpectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-03di-2944000000-431efb92dd6b4ef8117fSpectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-0a4i-1002900000-196e25f3fee6b4c0c1b9Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0a4l-3027900000-8bcaac6304f22421df0bSpectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-02tl-9742000000-4a57647def4127013cd1Spectrum
Toxicity Profile
Route of ExposureNot Available
Mechanism of ToxicityNot Available
MetabolismNot Available
Toxicity ValuesNot Available
Lethal DoseNot Available
Carcinogenicity (IARC Classification)Not Available
Uses/SourcesNot Available
Minimum Risk LevelNot Available
Health EffectsNot Available
SymptomsNot Available
TreatmentNot Available
Concentrations
Not Available
DrugBank IDDB00973
HMDB IDHMDB0015108
FooDB IDNot Available
Phenol Explorer IDNot Available
KNApSAcK IDNot Available
BiGG IDNot Available
BioCyc IDNot Available
METLIN IDNot Available
PDB IDNot Available
Wikipedia LinkEzetimibe
Chemspider ID132493
ChEBI ID49040
PubChem Compound ID150311
Kegg Compound IDNot Available
YMDB IDNot Available
ECMDB IDNot Available
References
Synthesis ReferenceNot Available
MSDSNot Available
General References
1. Garcia-Calvo M, Lisnock J, Bull HG, Hawes BE, Burnett DA, Braun MP, Crona JH, Davis HR Jr, Dean DC, Detmers PA, Graziano MP, Hughes M, Macintyre DE, Ogawa A, O'neill KA, Iyer SP, Shevell DE, Smith MM, Tang YS, Makarewicz AM, Ujjainwalla F, Altmann SW, Chapman KT, Thornberry NA: The target of ezetimibe is Niemann-Pick C1-Like 1 (NPC1L1). Proc Natl Acad Sci U S A. 2005 Jun 7;102(23):8132-7. Epub 2005 May 31.
2. https://www.ncbi.nlm.nih.gov/pubmed/?term=17587760
3. https://www.ncbi.nlm.nih.gov/pubmed/?term=18585981
4. https://www.ncbi.nlm.nih.gov/pubmed/?term=23219178
5. https://www.ncbi.nlm.nih.gov/pubmed/?term=23266293
6. https://www.ncbi.nlm.nih.gov/pubmed/?term=23317398
7. https://www.ncbi.nlm.nih.gov/pubmed/?term=23471229
8. https://www.ncbi.nlm.nih.gov/pubmed/?term=23510093
9. https://www.ncbi.nlm.nih.gov/pubmed/?term=23538020