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Record Information
Version1.0
Creation Date2014-09-11 05:16:39 UTC
Update Date2016-11-09 01:09:12 UTC
Accession NumberCHEM003746
Identification
Common NameTroglitazone
ClassSmall Molecule
DescriptionTroglitazone was withdrawn in 2000 due to risk of hepatotoxicity. It was superseded by pioglitazone and rosiglitazone.
Contaminant Sources
  • T3DB toxins
  • ToxCast & Tox21 Chemicals
Contaminant Type
  • Amide
  • Amine
  • Drug
  • Ether
  • Organic Compound
  • Synthetic Compound
Chemical Structure
Thumb
Synonyms
ValueSource
RezulinChEBI
RomglizoneChEBI
TroglitazonaChEBI
TroglitazonumChEBI
PrelayMeSH
Warner-lambert brand OF troglitazoneMeSH
Parke davis brand OF troglitazoneMeSH
Chemical FormulaC24H27NO5S
Average Molecular Mass441.540 g/mol
Monoisotopic Mass441.161 g/mol
CAS Registry Number97322-87-7
IUPAC Name5-({4-[(6-hydroxy-2,5,7,8-tetramethyl-3,4-dihydro-2H-1-benzopyran-2-yl)methoxy]phenyl}methyl)-1,3-thiazolidine-2,4-dione
Traditional Nametroglitazone
SMILESCC1=C(C)C2=C(CCC(C)(COC3=CC=C(CC4SC(=O)NC4=O)C=C3)O2)C(C)=C1O
InChI IdentifierInChI=1S/C24H27NO5S/c1-13-14(2)21-18(15(3)20(13)26)9-10-24(4,30-21)12-29-17-7-5-16(6-8-17)11-19-22(27)25-23(28)31-19/h5-8,19,26H,9-12H2,1-4H3,(H,25,27,28)
InChI KeyGXPHKUHSUJUWKP-UHFFFAOYSA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as 1-benzopyrans. These are organic aromatic compounds that 1-benzopyran, a bicyclic compound made up of a benzene ring fused to a pyran, so that the oxygen atom is at the 1-position.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassBenzopyrans
Sub Class1-benzopyrans
Direct Parent1-benzopyrans
Alternative Parents
Substituents
  • 1-benzopyran
  • Phenoxy compound
  • Phenol ether
  • Alkyl aryl ether
  • Thiazolidinedione
  • Monocyclic benzene moiety
  • Benzenoid
  • Dicarboximide
  • Thiazolidine
  • Carbonic acid derivative
  • Thiocarbamic acid derivative
  • Carboxylic acid derivative
  • Ether
  • Oxacycle
  • Azacycle
  • Organonitrogen compound
  • Organic oxide
  • Organopnictogen compound
  • Organic nitrogen compound
  • Organooxygen compound
  • Hydrocarbon derivative
  • Organic oxygen compound
  • Carbonyl group
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Membrane
Biofluid LocationsNot Available
Tissue LocationsNot Available
PathwaysNot Available
ApplicationsNot Available
Biological RolesNot Available
Chemical RolesNot Available
Physical Properties
StateSolid
AppearanceWhite powder.
Experimental Properties
PropertyValue
Melting Point184-186°C
Boiling PointNot Available
SolubilityNot Available
Predicted Properties
PropertyValueSource
Water Solubility0.0012 g/LALOGPS
logP4.16ALOGPS
logP5.5ChemAxon
logS-5.6ALOGPS
pKa (Strongest Acidic)6.61ChemAxon
pKa (Strongest Basic)-4.6ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area84.86 ŲChemAxon
Rotatable Bond Count5ChemAxon
Refractivity120.99 m³·mol⁻¹ChemAxon
Polarizability47.08 ųChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
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, Positivesplash10-0006-0430900000-ceb18bd79d0f6da79e7dView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-014i-0912100000-c1ddd0b2276cc0642c28View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0bt9-0910000000-70eed845667711a7ff74View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-0006-0133900000-d4c360adbc610d5363cfView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0v4l-4759300000-7eda5e5df7869dbcd569View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0006-9700000000-bbf919843d75c50ea813View in MoNA
Toxicity Profile
Route of ExposureAbsorbed rapidly. Food increases the extent of absorption by 30% to 85%.
Mechanism of ToxicityTroglitazone is a thiazolidinedione antidiabetic agent that lowers blood glucose by improving target cell response to insulin. It has a unique mechanism of action that is dependent on the presence of insulin for activity. Troglitazone decreases hepatic glucose output and increases insulin dependent glucose disposal in skeletal muscle. Its mechanism of action is thought to involve binding to nuclear receptors (PPAR) that regulate the transcription of a number of insulin responsive genes critical for the control of glucose and lipid metabolism. Troglitazone is a ligand to both PPAR‘± and PPAR‘_, with a highter affinity for PPAR‘_. The drug also contains an ‘±-tocopheroyl moiety, potentially giving it vitamin E-like activity. Troglitazone has been shown to reduce inflammation, and is associated with a decrase in nuclear factor kappa-B (NF-‘_B) and a concomitant increase in its inhibitor (I‘_B). NF-‘_B is an important cellular transcription regulator for the immune response. Unlike sulfonylureas, troglitazone is not an insulin secretagogue.
MetabolismA sulfate conjugate metabolite (Metabolite 1) and a quinone metabolite (Metabolite 3) have been detected in the plasma of healthy males. A glucuronide conjugate (Metabolite 2) has been detected in the urine and also in negligible amounts in the plasma. In healthy volunteers and in patients with type 2 diabetes, the steady-state concentration of Metabolite 1 is six to seven times that of troglitazone and Metabolite 3. In in vivo drug interaction studies, troglitazone has been shown to induce cytochrome P450 CYP3A4 at clinically relevant doses. Half Life: 16-34 hours
Toxicity ValuesNot Available
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesFor the treatment of Type II diabetes mellitus. It is used alone or in combination with a sulfonylurea, metformin, or insulin as an adjunct to diet and exercise.
Minimum Risk LevelNot Available
Health EffectsNot Available
SymptomsNot Available
TreatmentNot Available
Concentrations
Not Available
DrugBank IDDB00197
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 LinkTroglitazone
Chemspider IDNot Available
ChEBI ID9753
PubChem Compound ID5591
Kegg Compound IDNot Available
YMDB IDNot Available
ECMDB IDNot Available
References
Synthesis Reference

Krishnamurthi Vyas, Chebiyyam Prabhakar, Sreenivas Dharmaraja Rao, Mamillapalli Ramabadhra Sarma, Om Gaddam Reddy, Rajagopalan Ramanujam, Ranjan Chakrabarti, “Polymorphic forms of troglitazone having enhanced anti-diabetic activity and a process for their preparation.” U.S. Patent US5700820, issued June, 1992.

MSDSNot Available
General ReferencesNot Available