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Identification
NamePhenindione
Accession NumberDB00498  (APRD00166)
TypeSmall Molecule
GroupsApproved
Description

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)

Structure
Thumb
Synonyms
2-Phenyl-1,3-diketohydrindene
2-Phenyl-1,3-indandione
2-Phenyl-1,3(2H)-indenedione
Fenindiona
Fenindione
Phenindion
Phénindione
Phenindionum
PID
External Identifiers Not Available
Approved Prescription ProductsNot Available
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International Brands
NameCompany
DindevanSigma
FenindionSouriree
PhenindioneGoldshield
SoluthrombineCooper
Brand mixturesNot Available
SaltsNot Available
Categories
UNII5M7Y6274ZE
CAS number83-12-5
WeightAverage: 222.2387
Monoisotopic: 222.068079564
Chemical FormulaC15H10O2
InChI KeyInChIKey=NFBAXHOPROOJAW-UHFFFAOYSA-N
InChI
InChI=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
IUPAC Name
2-phenyl-2,3-dihydro-1H-indene-1,3-dione
SMILES
O=C1C(C(=O)C2=CC=CC=C12)C1=CC=CC=C1
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as indanones. These are compounds containing an indane ring bearing a ketone group.
KingdomOrganic compounds
Super ClassBenzenoids
ClassIndanes
Sub ClassIndanones
Direct ParentIndanones
Alternative Parents
Substituents
  • Indanone
  • Indanedione
  • Aryl alkyl ketone
  • Aryl ketone
  • 1,3-diketone
  • 1,3-dicarbonyl compound
  • Monocyclic benzene moiety
  • Ketone
  • Hydrocarbon derivative
  • Organooxygen compound
  • Carbonyl group
  • Aromatic homopolycyclic compound
Molecular FrameworkAromatic homopolycyclic compounds
External Descriptors
Pharmacology
IndicationFor the treatment of pulmonary embolism, cardiomyopathy, atrial fibrillation and flutter, cerebral embolism, mural thrombosis, and thrombophili. Also used for anticoagulant prophylaxis.
PharmacodynamicsPhenindione thins the blood by antagonizing vitamin K which is required for the production of clotting factors in the liver. Anticoagulants such as Phenindione have no direct effect on an established thrombus, nor do they reverse ischemic tissue damage (damage caused by an inadequate blood supply to an organ or part of the body). However, once a thrombus has occurred, the goal of anticoagulant treatment is to prevent further extension of the formed clot and prevent secondary thromboembolic complications which may result in serious and possibly fatal sequelae. Phenindione has actions similar to warfarin, but it is now rarely employed because of its higer incidence of severe adverse effects.
Mechanism of actionPhenindione 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.
Related Articles
AbsorptionAbsorbed slowly from the gastrointestinal tract.
Volume of distributionNot Available
Protein binding88%
Metabolism

Hepatic.

Route of eliminationNot Available
Half life5-10 hours
ClearanceNot Available
ToxicityOral, mouse: LD50 = 175 mg/kg; Oral, rat: LD50 = 163 mg/kg.
Affected organisms
  • Humans and other mammals
Pathways
PathwayCategorySMPDB ID
Phenindione Action PathwayDrug actionSMP00655
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+1.0
Blood Brain Barrier+0.9816
Caco-2 permeable+0.7697
P-glycoprotein substrateNon-substrate0.7593
P-glycoprotein inhibitor INon-inhibitor0.5461
P-glycoprotein inhibitor IINon-inhibitor0.8381
Renal organic cation transporterNon-inhibitor0.833
CYP450 2C9 substrateNon-substrate0.8036
CYP450 2D6 substrateNon-substrate0.9024
CYP450 3A4 substrateNon-substrate0.6947
CYP450 1A2 substrateInhibitor0.9013
CYP450 2C9 inhibitorNon-inhibitor0.5714
CYP450 2D6 inhibitorNon-inhibitor0.9231
CYP450 2C19 inhibitorNon-inhibitor0.7715
CYP450 3A4 inhibitorNon-inhibitor0.9141
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.598
Ames testAMES toxic0.7125
CarcinogenicityNon-carcinogens0.88
BiodegradationNot ready biodegradable0.8033
Rat acute toxicity3.1041 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9414
hERG inhibition (predictor II)Non-inhibitor0.9008
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
Manufacturers
  • Sanofi aventis us llc
PackagersNot Available
Dosage formsNot Available
PricesNot Available
PatentsNot Available
Properties
StateSolid
Experimental Properties
PropertyValueSource
melting point150 °CPhysProp
water solubility27 mg/L (at 20 °C)Not Available
logP2.90HANSCH,C ET AL. (1995)
Predicted Properties
PropertyValueSource
Water Solubility0.023 mg/mLALOGPS
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 Å2ChemAxon
Rotatable Bond Count1ChemAxon
Refractivity65.23 m3·mol-1ChemAxon
Polarizability23.24 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
Spectra
Spectrum TypeDescriptionSplash Key
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, NegativeNot Available
MSMass Spectrum (Electron Ionization)splash10-00di-4690000000-3b0da30c88d7d0ecf339View in MoNA
1D NMR1H NMR SpectrumNot Available
1D NMR13C NMR SpectrumNot Available
References
Synthesis ReferenceNot Available
General References
  1. Link [Link]
External Links
ATC CodesB01AA02
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSDownload (62.6 KB)
Interactions
Drug Interactions
Drug
AbciximabAbciximab may increase the anticoagulant activities of Phenindione.
AcenocoumarolPhenindione may increase the anticoagulant activities of Acenocoumarol.
Acetylsalicylic acidAcetylsalicylic acid may increase the anticoagulant activities of Phenindione.
AlteplaseAlteplase may increase the anticoagulant activities of Phenindione.
Aminosalicylic AcidAminosalicylic Acid may increase the anticoagulant activities of Phenindione.
AnagrelideAnagrelide may increase the anticoagulant activities of Phenindione.
ApixabanApixaban may increase the anticoagulant activities of Phenindione.
ArgatrobanPhenindione may increase the anticoagulant activities of Argatroban.
Bismuth SubsalicylateBismuth Subsalicylate may increase the anticoagulant activities of Phenindione.
BivalirudinPhenindione may increase the anticoagulant activities of Bivalirudin.
CaffeineCaffeine may increase the anticoagulant activities of Phenindione.
CangrelorCangrelor may increase the anticoagulant activities of Phenindione.
CelecoxibCelecoxib may increase the anticoagulant activities of Phenindione.
CilostazolCilostazol may increase the anticoagulant activities of Phenindione.
CitalopramCitalopram may increase the anticoagulant activities of Phenindione.
ClopidogrelClopidogrel may increase the anticoagulant activities of Phenindione.
Collagenase clostridium histolyticumThe risk or severity of adverse effects can be increased when Phenindione is combined with Collagenase clostridium histolyticum.
Cyproterone acetateThe therapeutic efficacy of Phenindione can be decreased when used in combination with Cyproterone acetate.
Dabigatran etexilateDabigatran etexilate may increase the anticoagulant activities of Phenindione.
DalteparinPhenindione may increase the anticoagulant activities of Dalteparin.
DanaparoidPhenindione may increase the anticoagulant activities of Danaparoid.
DasatinibDasatinib may increase the anticoagulant activities of Phenindione.
DeferasiroxThe risk or severity of adverse effects can be increased when Phenindione is combined with Deferasirox.
Deoxycholic AcidThe risk or severity of adverse effects can be increased when Phenindione is combined with Deoxycholic Acid.
DesirudinPhenindione may increase the anticoagulant activities of Desirudin.
DesogestrelDesogestrel may decrease the anticoagulant activities of Phenindione.
DesvenlafaxineDesvenlafaxine may increase the anticoagulant activities of Phenindione.
DiclofenacDiclofenac may increase the anticoagulant activities of Phenindione.
DienogestThe therapeutic efficacy of Phenindione can be decreased when used in combination with Dienogest.
DiflunisalDiflunisal may increase the anticoagulant activities of Phenindione.
DihydrocodeineDihydrocodeine may increase the anticoagulant activities of Phenindione.
DipyridamoleDipyridamole may increase the anticoagulant activities of Phenindione.
DrospirenoneDrospirenone may decrease the anticoagulant activities of Phenindione.
DuloxetineDuloxetine may increase the anticoagulant activities of Phenindione.
EdoxabanEdoxaban may increase the anticoagulant activities of Phenindione.
EnoxaparinPhenindione may increase the anticoagulant activities of Enoxaparin.
EpoprostenolThe risk or severity of adverse effects can be increased when Epoprostenol is combined with Phenindione.
EptifibatideEptifibatide may increase the anticoagulant activities of Phenindione.
EscitalopramEscitalopram may increase the anticoagulant activities of Phenindione.
EstradiolEstradiol may decrease the anticoagulant activities of Phenindione.
Estrone sulfateEstropipate may decrease the anticoagulant activities of Phenindione.
Ethinyl EstradiolEthinyl Estradiol may decrease the anticoagulant activities of Phenindione.
Ethynodiol diacetateEthynodiol may decrease the anticoagulant activities of Phenindione.
EtodolacEtodolac may increase the anticoagulant activities of Phenindione.
EtonogestrelThe therapeutic efficacy of Phenindione can be decreased when used in combination with Etonogestrel.
FenoprofenFenoprofen may increase the anticoagulant activities of Phenindione.
FloctafenineFloctafenine may increase the anticoagulant activities of Phenindione.
FluoxetineFluoxetine may increase the anticoagulant activities of Phenindione.
FlurbiprofenFlurbiprofen may increase the anticoagulant activities of Phenindione.
FluvoxamineFluvoxamine may increase the anticoagulant activities of Phenindione.
Fondaparinux sodiumPhenindione may increase the anticoagulant activities of Fondaparinux sodium.
HeparinPhenindione may increase the anticoagulant activities of Heparin.
Hydroxyprogesterone caproateThe therapeutic efficacy of Phenindione can be decreased when used in combination with Hydroxyprogesterone caproate.
Ibritumomab tiuxetanThe risk or severity of adverse effects can be increased when Phenindione is combined with Ibritumomab.
IbrutinibThe risk or severity of adverse effects can be increased when Ibrutinib is combined with Phenindione.
IbuprofenIbuprofen may increase the anticoagulant activities of Phenindione.
IcosapentIcosapent may increase the anticoagulant activities of Phenindione.
Icosapent ethylIcosapent ethyl may increase the anticoagulant activities of Phenindione.
IloprostThe risk or severity of adverse effects can be increased when Iloprost is combined with Phenindione.
IndomethacinIndomethacin may increase the anticoagulant activities of Phenindione.
KetoprofenKetoprofen may increase the anticoagulant activities of Phenindione.
KetorolacKetorolac may increase the anticoagulant activities of Phenindione.
LevomilnacipranLevomilnacipran may increase the anticoagulant activities of Phenindione.
LevonorgestrelThe therapeutic efficacy of Phenindione can be decreased when used in combination with Levonorgestrel.
Magnesium salicylateMagnesium salicylate may increase the anticoagulant activities of Phenindione.
Medroxyprogesterone acetateThe therapeutic efficacy of Phenindione can be decreased when used in combination with Medroxyprogesterone Acetate.
Mefenamic acidMefenamic acid may increase the anticoagulant activities of Phenindione.
Megestrol acetateThe therapeutic efficacy of Phenindione can be decreased when used in combination with Megestrol acetate.
MeloxicamMeloxicam may increase the anticoagulant activities of Phenindione.
MestranolMestranol may decrease the anticoagulant activities of Phenindione.
MilnacipranMilnacipran may increase the anticoagulant activities of Phenindione.
NabumetoneNabumetone may increase the anticoagulant activities of Phenindione.
NadroparinPhenindione may increase the anticoagulant activities of Nadroparin.
NaproxenNaproxen may increase the anticoagulant activities of Phenindione.
NintedanibThe risk or severity of adverse effects can be increased when Phenindione is combined with Nintedanib.
NorethisteroneThe therapeutic efficacy of Phenindione can be decreased when used in combination with Norethindrone.
NorgestimateNorgestimate may decrease the anticoagulant activities of Phenindione.
ObinutuzumabThe risk or severity of adverse effects can be increased when Phenindione is combined with Obinutuzumab.
Omega-3 fatty acidsOmega-3 fatty acids may increase the anticoagulant activities of Phenindione.
Omega-3-acid ethyl estersOmega-3-acid ethyl esters may increase the anticoagulant activities of Phenindione.
OxaprozinOxaprozin may increase the anticoagulant activities of Phenindione.
ParoxetineParoxetine may increase the anticoagulant activities of Phenindione.
Pentosan PolysulfatePentosan Polysulfate may increase the anticoagulant activities of Phenindione.
PiroxicamPiroxicam may increase the anticoagulant activities of Phenindione.
PrasugrelPrasugrel may increase the anticoagulant activities of Phenindione.
ProgesteroneThe therapeutic efficacy of Phenindione can be decreased when used in combination with Progesterone.
ReteplaseReteplase may increase the anticoagulant activities of Phenindione.
RivaroxabanPhenindione may increase the anticoagulant activities of Rivaroxaban.
SalsalateSalsalate may increase the anticoagulant activities of Phenindione.
SertralineSertraline may increase the anticoagulant activities of Phenindione.
SulindacSulindac may increase the anticoagulant activities of Phenindione.
TenecteplaseTenecteplase may increase the anticoagulant activities of Phenindione.
Tiaprofenic acidTiaprofenic acid may increase the anticoagulant activities of Phenindione.
TicagrelorTicagrelor may increase the anticoagulant activities of Phenindione.
TiclopidineTiclopidine may increase the anticoagulant activities of Phenindione.
TinzaparinPhenindione may increase the anticoagulant activities of Tinzaparin.
TipranavirTipranavir may increase the anticoagulant activities of Phenindione.
TirofibanTirofiban may increase the anticoagulant activities of Phenindione.
TolmetinTolmetin may increase the anticoagulant activities of Phenindione.
TositumomabThe risk or severity of adverse effects can be increased when Phenindione is combined with Tositumomab.
TreprostinilThe risk or severity of adverse effects can be increased when Treprostinil is combined with Phenindione.
VenlafaxineVenlafaxine may increase the anticoagulant activities of Phenindione.
VilazodoneVilazodone may increase the anticoagulant activities of Phenindione.
Vitamin EVitamin E may increase the anticoagulant activities of Phenindione.
VorapaxarThe risk or severity of adverse effects can be increased when Vorapaxar is combined with Phenindione.
VortioxetineVortioxetine may increase the anticoagulant activities of Phenindione.
WarfarinPhenindione may increase the anticoagulant activities of Warfarin.
Food InteractionsNot Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
inhibitor
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. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284 ]
  2. 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. [PubMed:17016423 ]
  3. Mentre F, Pousset F, Comets E, Plaud B, Diquet B, Montalescot G, Ankri A, Mallet A, Lechat P: Population pharmacokinetic-pharmacodynamic analysis of fluindione in patients. Clin Pharmacol Ther. 1998 Jan;63(1):64-78. [PubMed:9465843 ]
  4. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]
Comments
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Drug created on June 13, 2005 07:24 / Updated on August 17, 2016 12:23