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Record Information
Version2.0
Creation Date2009-07-23 18:26:19 UTC
Update Date2014-12-24 20:25:59 UTC
Accession NumberT3D3105
Identification
Common NamePhenprocoumon
ClassSmall Molecule
DescriptionPhenprocoumon is only found in individuals that have used or taken this drug. It is a coumarin derivative that acts as a long acting oral anticoagulant. [PubChem] Phenprocoumon 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
3-(1'-Phenyl-propyl)-4-oxycoumarin
3-(1-Phenylpropyl)-4-hydroxycoumarin
3-(alpha-Ethylbenzyl)-4-hydroxycoumarin
3-(alpha-Phenylpropyl)-4-hydroxycoumarin
4-Hydroxy-3-(1-phenylpropyl)-2H-1-benzopyran-2-one
4-Hydroxy-3-(1-phenylpropyl)-2H-chromen-2-one
Falithrom
Fenprocumon
Fenprocumone
Marcoumar
Marcumar
Phenprocoumarol
Phenprocoumarole
Phenprocoumone
Phenprocoumonum
Phenprocumone
Chemical FormulaC18H16O3
Average Molecular Mass280.318 g/mol
Monoisotopic Mass280.110 g/mol
CAS Registry Number435-97-2
IUPAC Name4-hydroxy-3-(1-phenylpropyl)-2H-chromen-2-one
Traditional Namephenprocoumon
SMILESCCC(C1=CC=CC=C1)C1=C(O)C2=CC=CC=C2OC1=O
InChI IdentifierInChI=1/C18H16O3/c1-2-13(12-8-4-3-5-9-12)16-17(19)14-10-6-7-11-15(14)21-18(16)20/h3-11,13,19H,2H2,1H3
InChI KeyInChIKey=DQDAYGNAKTZFIW-UHFFFAOYNA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as 4-hydroxycoumarins. These are coumarins that contain one or more hydroxyl groups attached to C4-position the coumarin skeleton.
KingdomOrganic compounds
Super ClassPhenylpropanoids and polyketides
ClassCoumarins and derivatives
Sub ClassHydroxycoumarins
Direct Parent4-hydroxycoumarins
Alternative Parents
Substituents
  • 4-hydroxycoumarin
  • Benzopyran
  • 1-benzopyran
  • Phenylpropane
  • Pyranone
  • Monocyclic benzene moiety
  • Benzenoid
  • Pyran
  • Heteroaromatic compound
  • Vinylogous acid
  • Lactone
  • Oxacycle
  • Organoheterocyclic compound
  • Organooxygen compound
  • Organic oxygen compound
  • Hydrocarbon derivative
  • Organic oxide
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Extracellular
  • Membrane
Biofluid LocationsNot Available
Tissue LocationsNot Available
PathwaysNot Available
Applications
Biological Roles
Chemical Roles
Physical Properties
StateSolid
AppearanceWhite powder.
Experimental Properties
PropertyValue
Melting Point179.5°C
Boiling PointNot Available
Solubility12.9 mg/L
LogP3.62
Predicted Properties
PropertyValueSource
Water Solubility0.049 g/LALOGPS
logP3.81ALOGPS
logP3.74ChemAxon
logS-3.8ALOGPS
pKa (Strongest Acidic)6.44ChemAxon
pKa (Strongest Basic)-6.5ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area46.53 ŲChemAxon
Rotatable Bond Count3ChemAxon
Refractivity81.64 m³·mol⁻¹ChemAxon
Polarizability29.92 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, Positivesplash10-0gk9-1390000000-b8adf6e29e27ba0e0032JSpectraViewer
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (1 TMS) - 70eV, Positivesplash10-00fr-6659000000-d206d323114210822b66JSpectraViewer
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 GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, PositiveNot AvailableJSpectraViewer
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (TBDMS_1_1) - 70eV, PositiveNot AvailableJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-001i-0190000000-3363e5ab875f54ecfdbeJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-001i-0390000000-5d8ad9702c75c69b0036JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-06di-4940000000-8a3c1778a9c418538afbJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-004i-0090000000-b940e8a82db8a93a6124JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-01t9-0490000000-9f94c9b5f041d6204096JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-054o-8960000000-ce2be44f7678a353e146JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-001i-0190000000-e4c63991e04960d28471JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-001i-2390000000-7d5deb49a774d3652362JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-00b9-7940000000-2379ac94fd9f7accb460JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-004i-0090000000-095b46a5a952085bd428JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-03fr-1980000000-5cc9eb499f441aa93168JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-056r-4970000000-d20cae73879a28552702JSpectraViewer
Toxicity Profile
Route of ExposureIngestion (4) ; dermal (4). Bioavailability is close to 100%.
Mechanism of ToxicityPhenprocoumon 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. (1)
MetabolismPhenprocoumon is stereoselectively metabolized by hepatic microsomal enzymes (cytochrome P-450) to inactive hydroxylated metabolites (predominant route) and by reductases to reduced metabolites. Cytochrome P450 2C9 is the principal form of human liver P-450 responsible for metabolism. Half Life: 5-6 days
Toxicity ValuesNot Available
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesPhenprocoumon is an anticoagulant drug. (3) Used for the prevention and treatment of thromboembolic disease including venous thrombosis, thromboembolism, and pulmonary embolism as well as for the prevention of ischemic stroke in patients with atrial fibrillation (AF).
Minimum Risk LevelNot Available
Health EffectsPhenprocoumon is an anticoagulant and may cause internal bleeding, leading to shock, loss of consciousness, and eventually death. (2)
SymptomsSymptoms of overdose includes suspected or overt abnormal bleeding (e.g., appearance of blood in stools or urine, hematuria, excessive menstrual bleeding, melena, petechiae, excessive bruising or persistent oozing from superficial injuries).
TreatmentThe primary antidote to phenprocoumon 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 phenprocoumon 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 IDDB00946
HMDB IDHMDB15081
PubChem Compound ID54680692
ChEMBL IDCHEMBL1465
ChemSpider ID10441592
KEGG IDNot Available
UniProt IDNot Available
OMIM ID
ChEBI ID50438
BioCyc IDNot Available
CTD IDNot Available
Stitch IDPhenprocoumon
PDB IDNot Available
ACToR IDNot Available
Wikipedia LinkPhenprocoumon
References
Synthesis ReferenceNot Available
MSDST3D3105.pdf
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. Phenprocoumon. Last Updated 19 December 2008. [Link]
  4. 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 ]
General Function:
Not Available
Specific Function:
Functions as transport protein in the blood stream. Binds various ligands in the interior of its beta-barrel domain. Also binds synthetic drugs and influences their distribution and availability in the body. Appears to function in modulating the activity of the immune system during the acute-phase reaction.
Gene Name:
ORM1
Uniprot ID:
P02763
Molecular Weight:
23511.38 Da
General Function:
Toxic substance binding
Specific Function:
Serum albumin, the main protein of plasma, has a good binding capacity for water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs. Its main function is the regulation of the colloidal osmotic pressure of blood. Major zinc transporter in plasma, typically binds about 80% of all plasma zinc.
Gene Name:
ALB
Uniprot ID:
P02768
Molecular Weight:
69365.94 Da