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Record Information
Version4.0
Creation Date2006-10-17 09:52:37 UTC
Update Date2017-09-27 08:24:33 UTC
HMDB IDHMDB0005031
Secondary Accession Numbers
  • HMDB05031
Metabolite Identification
Common NameRosiglitazone
DescriptionRosiglitazone is an anti-diabetic drug from the thiazolidinedione class. Like other thiazolidinediones, its mechanism of action is by activation of the intracellular receptor class of the peroxisome proliferator-activated receptors (PPARs), specifically PPAR-gamma. Rosiglitazone is a pure ligand of PPAR-gamma, and has no PPAR-alpha-binding action. Apart from its effect on insulin resistance, it appears to have an anti-inflammatory effect: nuclear factor kappa-B (NFκB) levels fall and inhibitor (IκB) levels increase in patients on rosiglitazone (Mohanty et al). It increases glyceroneogenesis and reduces the release of free fatty acids from adipocytes; Rosiglitazone is an anti-diabetic drug from the thiazolidinedione class. It is being marketed as Avandia by the pharmaceutical company GlaxoSmithKline, both as a standalone preparation and in combination with metformin (Avandamet). Another combination drug approved by the FDA is Avandaryl (with glimepiride); Like other thiazolidinediones, its mechanism of action is by activation of the intracellular receptor class of the peroxisome proliferator-activated receptors (PPARs), specifically PPAR-gamma. Rosiglitazone is a pure ligand of PPAR-gamma, and has no PPAR-alpha binding action. Apart from its effect on insulin resistance, it appears to have an anti-inflammatory effect: nuclear factor kappa-B (NFkB) levels fall and inhibitor (IkB) levels increase in patients on rosiglitazone (Mohanty et al). It increases glyceroneogenesis and reduces the release of free fatty acids from adipocytes.
Structure
Thumb
Synonyms
ValueSource
5-((4-(2-(Methyl-2-pyridinylamino)ethoxy)phenyl)methyl)-2,4-thiazolidinedioneChEBI
BRL-49653ChEBI
RosiglitazonaChEBI
RosiglitazonumChEBI
AvandiaHMDB
Rosiglitazone maleateHMDB
RosiglizoleHMDB
5-((4-(2-Methyl-2-(pyridinylamino)ethoxy)phenyl)methyl)-2,4-thiazolidinedione-2-butenedioateMeSH
GlaxoSmithKline brand OF rosiglitazone maleateMeSH
SmithKline beecham brand OF rosiglitazone maleateMeSH
glaxo Wellcome brand OF rosiglitazone maleateMeSH
Chemical FormulaC18H19N3O3S
Average Molecular Weight357.427
Monoisotopic Molecular Weight357.114712179
IUPAC Name5-[(4-{2-[methyl(pyridin-2-yl)amino]ethoxy}phenyl)methyl]-1,3-thiazolidine-2,4-dione
Traditional Namerosiglitazone
CAS Registry Number122320-73-4
SMILES
CN(CCOC1=CC=C(CC2SC(=O)NC2=O)C=C1)C1=CC=CC=N1
InChI Identifier
InChI=1S/C18H19N3O3S/c1-21(16-4-2-3-9-19-16)10-11-24-14-7-5-13(6-8-14)12-15-17(22)20-18(23)25-15/h2-9,15H,10-12H2,1H3,(H,20,22,23)
InChI KeyYASAKCUCGLMORW-UHFFFAOYSA-N
Chemical Taxonomy
DescriptionThis compound belongs to the class of chemical entities known as phenol ethers. These are aromatic compounds containing an ether group substituted with a benzene ring.
KingdomChemical entities
Super ClassOrganic compounds
ClassBenzenoids
Sub ClassPhenol ethers
Direct ParentPhenol ethers
Alternative Parents
Substituents
  • Phenoxy compound
  • Phenol ether
  • Dialkylarylamine
  • Alkyl aryl ether
  • Aminopyridine
  • Monocyclic benzene moiety
  • Imidolactam
  • Pyridine
  • Heteroaromatic compound
  • Meta-thiazoline
  • Ether
  • Azacycle
  • Organoheterocyclic compound
  • Organic 1,3-dipolar compound
  • Propargyl-type 1,3-dipolar organic compound
  • Organic nitrogen compound
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organonitrogen compound
  • Organic oxide
  • Carbonyl group
  • Organopnictogen compound
  • Organic oxygen compound
  • Aromatic heteromonocyclic compound
Molecular FrameworkAromatic heteromonocyclic compounds
External Descriptors
Ontology
Process

Naturally occurring process:

  Biological process:

    Biochemical pathway:

Disposition

Biological Location:

  Subcellular:

Role

Industrial application:

  Pharmaceutical industry:

Physical Properties
StateSolid
Experimental Properties
PropertyValueReference
Melting PointNot AvailableNot Available
Boiling PointNot AvailableNot Available
Water SolubilityNot AvailableNot Available
LogPNot AvailableNot Available
Predicted Properties
PropertyValueSource
Water Solubility0.038 g/LALOGPS
logP2.95ALOGPS
logP2.45ChemAxon
logS-4ALOGPS
pKa (Strongest Acidic)6.84ChemAxon
pKa (Strongest Basic)6.23ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area71.53 ŲChemAxon
Rotatable Bond Count7ChemAxon
Refractivity97.79 m³·mol⁻¹ChemAxon
Polarizability37.8 ųChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash Key
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, PositiveNot AvailableView in JSpectraViewer
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-qTof , Positivesplash10-0a4i-0109000000-d527d5c2b5f1de352264View in MoNA
LC-MS/MSLC-MS/MS Spectrum - , positivesplash10-0a4i-0109000000-d527d5c2b5f1de352264View in MoNA
LC-MS/MSLC-MS/MS Spectrum - , positivesplash10-0a4r-1609000000-585d240b82e4a1918a29View in MoNA
LC-MS/MSLC-MS/MS Spectrum - , positivesplash10-0a4i-0309000000-a9fa2307075b611cffccView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-0a4i-0119000000-afcd19b8a0a922a55f1aView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-052r-0941000000-369864aa78ee259dca92View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0a4i-1910000000-f9a7e77fcdf7ededf79cView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-0a4i-0439000000-ab505f9372d95dd2a762View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0k9l-4792000000-bfe60ce181bc6c7314cbView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0006-9500000000-9699ab9cf1188cacce3fView in MoNA
Biological Properties
Cellular Locations
  • Membrane (predicted from logP)
Biofluid LocationsNot Available
Tissue LocationNot Available
Pathways
NameSMPDB/PathwhizKEGG
Rosiglitazone Metabolism PathwayPw000629Pw000629 greyscalePw000629 simpleNot Available
Displaying 1 entry
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
Associated Disorders and Diseases
Disease ReferencesNone
Associated OMIM IDsNone
DrugBank IDNot Available
DrugBank Metabolite IDNot Available
Phenol Explorer Compound IDNot Available
Phenol Explorer Metabolite IDNot Available
FoodDB IDFDB023598
KNApSAcK IDNot Available
Chemspider ID70383
KEGG Compound IDNot Available
BioCyc IDNot Available
BiGG IDNot Available
Wikipedia LinkRosiglitazone
METLIN IDNot Available
PubChem Compound77999
PDB IDNot Available
ChEBI ID50122
References
Synthesis Reference Reddy, Manne Satyanarayana; Rajan, Srinivasan Thirumalai; Rao, Mandava Venkata Naga Brahmeswar. An improved process for the preparation of 5-{4-[2-(N-methyl-N-(2-pyridyl)amino)ethoxy]benzyl}-2,4-thiazolidinedione maleate (Rosiglitazone maleate). (Dr. R
Material Safety Data Sheet (MSDS)Download (PDF)
General ReferencesNot Available

Enzymes

General function:
Involved in monooxygenase activity
Specific function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. This enzyme contributes to the wide pharmacokinetics variability of the metabolism of drugs such as S-warfarin, diclofenac, phenytoin, tolbutamide and losartan.
Gene Name:
CYP2C9
Uniprot ID:
P11712
Molecular weight:
55627.365
General function:
Involved in monooxygenase activity
Specific function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. In the epoxidation of arachidonic acid it generates only 14,15- and 11,12-cis-epoxyeicosatrienoic acids. It is the principal enzyme responsible for the metabolism the anti-cancer drug paclitaxel (taxol).
Gene Name:
CYP2C8
Uniprot ID:
P10632
Molecular weight:
55824.275
General function:
Involved in DNA binding
Specific function:
Receptor that binds peroxisome proliferators such as hypolipidemic drugs and fatty acids. Once activated by a ligand, the receptor binds to a promoter element in the gene for acyl-CoA oxidase and activates its transcription. It therefore controls the peroxisomal beta-oxidation pathway of fatty acids. Key regulator of adipocyte differentiation and glucose homeostasis
Gene Name:
PPARG
Uniprot ID:
P37231
Molecular weight:
57619.6