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Record Information
Version2.0
Creation Date2009-07-23 18:26:20 UTC
Update Date2014-12-24 20:25:59 UTC
Accession NumberT3D3107
Identification
Common NamePhenindione
ClassSmall Molecule
DescriptionPhenindione is only found in individuals that have used or taken this drug. It is an indandione that has been used as an anticoagulant. Phenindione has actions similar to warfarin, but it is now rarely employed because of its higher incidence of severe adverse effects. (From Martindale, The Extra Pharmacopoeia, 30th ed, p234). Phenindione inhibits vitamin K reductase, resulting in depletion of the reduced form of vitamin K (vitamin KH2). As vitamin K is a cofactor for the carboxylation of glutamate residues on the N-terminal regions of vitamin K-dependent proteins, this limits the gamma-carboxylation and subsequent activation of the vitamin K-dependent coagulant proteins. The synthesis of vitamin K-dependent coagulation factors II, VII, IX, and X and anticoagulant proteins C and S is inhibited. Depression of three of the four vitamin K-dependent coagulation factors (factors II, VII, and X) results in decreased prothrombin levels and a decrease in the amount of thrombin generated and bound to fibrin. This reduces the thrombogenicity of clots.
Compound Type
  • Anticoagulant
  • Aromatic Hydrocarbon
  • Drug
  • Ester
  • Metabolite
  • Organic Compound
  • Synthetic Compound
Chemical Structure
Thumb
Synonyms
Synonym
2-Phenyl-1,3(2H)-indenedione
2-Phenyl-1,3-diketohydrindene
2-Phenyl-1,3-indandione
Dindevan
Fenindion
Fenindiona
Fenindione
Phenindion
Phénindione
Phenindionum
PID
Soluthrombine
Chemical FormulaC15H10O2
Average Molecular Mass222.239 g/mol
Monoisotopic Mass222.068 g/mol
CAS Registry Number83-12-5
IUPAC Name2-phenyl-2,3-dihydro-1H-indene-1,3-dione
Traditional Nameindon
SMILESO=C1C(C(=O)C2=CC=CC=C12)C1=CC=CC=C1
InChI IdentifierInChI=1S/C15H10O2/c16-14-11-8-4-5-9-12(11)15(17)13(14)10-6-2-1-3-7-10/h1-9,13H
InChI KeyInChIKey=NFBAXHOPROOJAW-UHFFFAOYSA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as indanediones. Indanediones are compounds containing an indane ring bearing two ketone groups.
KingdomOrganic compounds
Super ClassBenzenoids
ClassIndanes
Sub ClassIndanones
Direct ParentIndanediones
Alternative Parents
Substituents
  • Indanedione
  • Aryl alkyl ketone
  • Aryl ketone
  • 1,3-diketone
  • 1,3-dicarbonyl compound
  • Monocyclic benzene moiety
  • Ketone
  • Organic oxygen compound
  • Organic oxide
  • Hydrocarbon derivative
  • Organooxygen compound
  • Aromatic homopolycyclic compound
Molecular FrameworkAromatic homopolycyclic compounds
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Membrane
Biofluid LocationsNot Available
Tissue LocationsNot Available
PathwaysNot Available
Applications
Biological RolesNot Available
Chemical RolesNot Available
Physical Properties
StateSolid
AppearanceWhite powder.
Experimental Properties
PropertyValue
Melting Point150°C
Boiling PointNot Available
Solubility27 mg/L (at 20°C)
LogP2.9
Predicted Properties
PropertyValueSource
Water Solubility0.023 g/LALOGPS
logP3.1ALOGPS
logP2.88ChemAxon
logS-4ALOGPS
pKa (Strongest Acidic)4.88ChemAxon
pKa (Strongest Basic)-7.5ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area34.14 ŲChemAxon
Rotatable Bond Count1ChemAxon
Refractivity65.23 m³·mol⁻¹ChemAxon
Polarizability23.24 ųChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash KeyView
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-006x-8950000000-db616a8e7e559a5a5f6fJSpectraViewer
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, PositiveNot AvailableJSpectraViewer
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, PositiveNot AvailableJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-00di-0090000000-9b298f1072fd790bda04JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-00di-3390000000-11fefa0e023507256e68JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0a4l-9460000000-25e9eb850e8f08d73284JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-00di-0090000000-3ff702d3fba3b4ba61c9JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-00di-0090000000-782f754ab0024fcab923JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0gi9-5940000000-5905bd66b8f78a2f70a3JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-00di-0090000000-4526ea1529fb7968e1f9JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-00di-2390000000-dafe0249a10821f9782fJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0006-9100000000-ee672ba3244610e83f29JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-00di-0090000000-67222288c14ba81150ceJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-00di-0090000000-67222288c14ba81150ceJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-01c0-0920000000-f427c2360b8ee97f9d00JSpectraViewer
MSMass Spectrum (Electron Ionization)splash10-00di-4690000000-3b0da30c88d7d0ecf339JSpectraViewer | MoNA
1D NMR1H NMR SpectrumNot AvailableJSpectraViewer
1D NMR13C NMR SpectrumNot AvailableJSpectraViewer
Toxicity Profile
Route of ExposureIngestion (5) ; dermal (5). Absorbed slowly from the gastrointestinal tract.
Mechanism of ToxicityPhenindione inhibits vitamin K reductase, resulting in depletion of the reduced form of vitamin K (vitamin KH2). As vitamin K is a cofactor for the carboxylation of glutamate residues on the N-terminal regions of vitamin K-dependent proteins, this limits the gamma-carboxylation and subsequent activation of the vitamin K-dependent coagulant proteins. The synthesis of vitamin K-dependent coagulation factors II, VII, IX, and X and anticoagulant proteins C and S is inhibited. Depression of three of the four vitamin K-dependent coagulation factors (factors II, VII, and X) results in decresed prothrombin levels and a decrease in the amount of thrombin generated and bound to fibrin. This reduces the thrombogenicity of clots. (1)
MetabolismHepatic. Half Life: 5-10 hours
Toxicity ValuesOral, mouse: LD50 = 175 mg/kg; Oral, rat: LD50 = 163 mg/kg.
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesPhenindione is an anticoagulant drug derived from coumarin. (3) For the treatment of pulmonary embolism, cardiomyopathy, atrial fibrillation and flutter, cerebral embolism, mural thrombosis, and thrombophili. Also used for anticoagulant prophylaxis.
Minimum Risk LevelNot Available
Health EffectsPhenindione is an anticoagulant and may cause internal bleeding, leading to shock, loss of consciousness, and eventually death. (2)
SymptomsPhenindione may cause bleeding complications. (2)
TreatmentThe primary antidote to phenindione poisoning is immediate administration of vitamin K1 (initially slow intravenous injections of 10-25 mg repeated all 3-6 hours until normalisation of the prothrombin time; then 10 mg orally four times daily as a "maintenance dose"). It is an extremely effective antidote, provided the poisoning is caught before too much damage has been done to the victim's circulatory system. At high doses phenindione can affect the body for many months, and the antidote must be administered regularly for a long period of time. (2)
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDDB00498
HMDB IDHMDB14641
PubChem Compound ID4760
ChEMBL IDCHEMBL711
ChemSpider ID4596
KEGG IDC07584
UniProt IDNot Available
OMIM ID
ChEBI ID8066
BioCyc IDNot Available
CTD IDNot Available
Stitch IDPhenindione
PDB IDNot Available
ACToR IDNot Available
Wikipedia LinkPhenindione
References
Synthesis ReferenceNot Available
MSDSLink
General References
  1. Wishart DS, Knox C, Guo AC, Cheng D, Shrivastava S, Tzur D, Gautam B, Hassanali M: DrugBank: a knowledgebase for drugs, drug actions and drug targets. Nucleic Acids Res. 2008 Jan;36(Database issue):D901-6. Epub 2007 Nov 29. [18048412 ]
  2. Wikipedia. Brodifacoum. Last Updated 22 June 2009. [Link]
  3. Wikipedia. Phenindione. Last Updated 30 June 2009. [Link]
  4. Patient UK (2009). Phenindione. [Link]
  5. Wikipedia. Phytotoxin. Last Updated 7 August 2009. [Link]
Gene Regulation
Up-Regulated GenesNot Available
Down-Regulated GenesNot Available

Targets

General Function:
Vitamin-k-epoxide reductase (warfarin-sensitive) activity
Specific Function:
Involved in vitamin K metabolism. Catalytic subunit of the vitamin K epoxide reductase (VKOR) complex which reduces inactive vitamin K 2,3-epoxide to active vitamin K. Vitamin K is required for the gamma-carboxylation of various proteins, including clotting factors, and is required for normal blood coagulation, but also for normal bone development.
Gene Name:
VKORC1
Uniprot ID:
Q9BQB6
Molecular Weight:
18234.3 Da
References
  1. Wishart DS, Knox C, Guo AC, Cheng D, Shrivastava S, Tzur D, Gautam B, Hassanali M: DrugBank: a knowledgebase for drugs, drug actions and drug targets. Nucleic Acids Res. 2008 Jan;36(Database issue):D901-6. Epub 2007 Nov 29. [18048412 ]
  2. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
  3. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [17016423 ]