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Phenprocoumon

July 24, 2017
Common Name

Phenprocoumon Description

Phenprocoumon is only found in individuals that have used or taken this drug. It is a coumarin derivative that acts as a long acting oral anticoagliant. [PubChem]Phenprocoumon inhibits vitamin K reductase, resliting 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 coagliant proteins. The synthesis of vitamin K-dependent coagliation factors II, VII, IX, and X and anticoagliant proteins C and S is inhibited. Depression of three of the four vitamin K-dependent coagliation factors (factors II, VII, and X) reslits in decreased prothrombin levels and a decrease in the amount of thrombin generated and bound to fibrin. This reduces the thrombogenicity of clots. Structure

MOLSDF3D-SDFPDBSMILESInChI View 3D Structure

Synonyms

Value Source 3-(1'-Phenyl-propyl)-4-oxycoumarinChEBI 3-(1-Phenylpropyl)-4-hydroxycoumarinChEBI 3-(alpha-Ethylbenzyl)-4-hydroxycoumarinChEBI 3-(alpha-Phenylpropyl)-4-hydroxycoumarinChEBI 4-Hydroxy-3-(1-phenylpropyl)-2H-1-benzopyran-2-oneChEBI 4-Hydroxy-3-(1-phenylpropyl)-2H-chromen-2-oneChEBI FenprocumonChEBI FenprocumoneChEBI PhenprocoumarolChEBI PhenprocoumaroleChEBI PhenprocoumoneChEBI PhenprocoumonumChEBI PhenprocumoneChEBI 3-(a-Ethylbenzyl)-4-hydroxycoumarinGenerator 3-(α-ethylbenzyl)-4-hydroxycoumarinGenerator 3-(a-Phenylpropyl)-4-hydroxycoumarinGenerator 3-(α-phenylpropyl)-4-hydroxycoumarinGenerator FalithromMeSH MarcoumarMeSH PhenprocoumalolMeSH PhenylpropylhydroxycumarinumMeSH MarcumarMeSH PhenprogrammaMeSH Hexal brand OF phenprocoumonMeSH LiquamarMeSH Wörwag brand OF phenprocoumonMeSH Roche brand OF phenprocoumonMeSH

Chemical Formlia

C18H16O3 Average Molecliar Weight

280.3178 Monoisotopic Molecliar Weight

280.109944378 IUPAC Name

4-hydroxy-3-(1-phenylpropyl)-2H-chromen-2-one Traditional Name

phenprocoumon CAS Registry Number

435-97-2 SMILES

CCC(C1=CC=CC=C1)C1=C(O)C2=C(OC1=O)C=CC=C2

InChI Identifier

InChI=1S/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 Key

DQDAYGNAKTZFIW-UHFFFAOYSA-N Chemical Taxonomy Description

This compound belongs to the class of chemical entities known as 4-hydroxycoumarins. These are coumarins that contain one or more hydroxyl groups attached to C4-position the coumarin skeleton. Kingdom

Chemical entities Super Class

Organic compounds Class

Phenylpropanoids and polyketides Sub Class

Coumarins and derivatives Direct Parent

4-hydroxycoumarins Alternative Parents

  • 1-benzopyrans
  • Phenylpropanes
  • Pyranones and derivatives
  • Vinylogous acids
  • Heteroaromatic compounds
  • Lactones
  • Oxacyclic compounds
  • Organooxygen compounds
  • Organic oxides
  • Hydrocarbon derivatives

    • 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

    • Molecliar Framework

    Aromatic heteropolycyclic compounds External Descriptors

  • hydroxycoumarin (CHEBI:50438 )

    • Ontology Status

    Expected but not Quantified Origin

  • Drug

    • Biofunction

  • Anticoagliants

    • Application

  • Pharmaceutical

    • Cellliar locations

  • Extracellliar
  • Membrane

    • Physical Properties State

    Solid Experimental Properties

    Property Value Reference Melting Point179.5 °CNot Available Boiling PointNot AvailableNot Available Water Solubility4.86e-02 g/LNot Available LogP4.4Not Available

    Predicted Properties

    Property Value Source Water Solubility0.049 mg/mLALOGPS 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 Å2ChemAxon Rotatable Bond Count3ChemAxon Refractivity81.64 m3·mol-1ChemAxon Polarizability29.92 Å3ChemAxon Number of Rings3ChemAxon Bioavailability1ChemAxon Rlie of FiveYesChemAxon Ghose FilterYesChemAxon Vebers RlieYesChemAxon MDDR-like RlieYesChemAxon

    Spectra Spectra

    Spectrum Type Description Splash Key Predicted LC-MS/MS

    Predicted LC-MS/MS Spectrum – 10V, PositiveNot Available Predicted LC-MS/MS

    Predicted LC-MS/MS Spectrum – 20V, PositiveNot Available Predicted LC-MS/MS

    Predicted LC-MS/MS Spectrum – 40V, PositiveNot Available Predicted LC-MS/MS

    Predicted LC-MS/MS Spectrum – 10V, NegativeNot Available Predicted LC-MS/MS

    Predicted LC-MS/MS Spectrum – 20V, NegativeNot Available Predicted LC-MS/MS

    Predicted LC-MS/MS Spectrum – 40V, NegativeNot Available

    Biological Properties Cellliar Locations

  • Extracellliar
  • Membrane

    • Biofluid Locations

  • Blood
  • Urine

    • Tissue Location

    Not Available Pathways

    Name SMPDB Link KEGG Link Phenprocoumon PathwaySMP00271Not Available

    Normal Concentrations

    Biofluid Status Value Age Sex Condition Reference Details BloodExpected but not Quantified Not AvailableNot AvailableTaking drug identified by DrugBank entry DB00946

  • 21059682

    • details UrineExpected but not Quantified Not AvailableNot AvailableTaking drug identified by DrugBank entry DB00946

  • 21059682

    • details

    Abnormal Concentrations

    Not Available Predicted Concentrations

    Biofluid Value Original age Original sex Original condition Comments Blood0-4 uMAdlit (>18 years old)BothNormalPredicted based on drug qualities Blood0-2 umol/mmol creatinineAdlit (>18 years old)BothNormalPredicted based on drug qualities

    Associated Disorders and Diseases Disease References

    None Associated OMIM IDs

    None External Links DrugBank ID

    DB00946 DrugBank Metabolite ID

    Not Available Phenol Explorer Compound ID

    Not Available Phenol Explorer Metabolite ID

    Not Available FoodDB ID

    Not Available KNApSAcK ID

    Not Available Chemspider ID

    10441592 KEGG Compound ID

    Not Available BioCyc ID

    Not Available BiGG ID

    Not Available Wikipedia Link

    Phenprocoumon NuGOwiki Link

    HMDB15081 Metagene Link

    HMDB15081 METLIN ID

    Not Available PubChem Compound

    54680692 PDB ID

    Not Available ChEBI ID

    50438

    Product: SN 3

    References Synthesis Reference Not Available Material Safety Data Sheet (MSDS) Not Available General References Not 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 performs a variety of oxidation reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1-hydroxylation and midazolam 4-hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Acts as a 1,8-cineole 2-exo-monooxygenase. The enzyme also hydroxylates etoposide.
    Gene Name:
    CYP3A4
    Uniprot ID:
    P08684
    Molecular weight:
    57255.585
    References
    1. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. [PubMed:19515014 ]
    2. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]
    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
    References
    1. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. [PubMed:19515014 ]
    2. Schalekamp T, Brasse BP, Roijers JF, van Meegen E, van der Meer FJ, van Wijk EM, Egberts AC, de Boer A: VKORC1 and CYP2C9 genotypes and phenprocoumon anticoagulation status: interaction between both genotypes affects dose requirement. Clin Pharmacol Ther. 2007 Feb;81(2):185-93. Epub 2006 Dec 27. [PubMed:17192772 ]
    3. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]
    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
    References
    1. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. [PubMed:19515014 ]
    2. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]
    General function:
    Involved in vitamin-K-epoxide reductase (warfarin-sensi
    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.
    Gene Name:
    VKORC1
    Uniprot ID:
    Q9BQB6
    Molecular weight:
    18234.3
    References
    1. Schalekamp T, Brasse BP, Roijers JF, van Meegen E, van der Meer FJ, van Wijk EM, Egberts AC, de Boer A: VKORC1 and CYP2C9 genotypes and phenprocoumon anticoagulation status: interaction between both genotypes affects dose requirement. Clin Pharmacol Ther. 2007 Feb;81(2):185-93. Epub 2006 Dec 27. [PubMed:17192772 ]
    2. Reitsma PH, van der Heijden JF, Groot AP, Rosendaal FR, Buller HR: A C1173T dimorphism in the VKORC1 gene determines coumarin sensitivity and bleeding risk. PLoS Med. 2005 Oct;2(10):e312. Epub 2005 Oct 11. [PubMed:16201835 ]
    3. Thijssen HH, Baars LG: Microsomal warfarin binding and vitamin K 2,3-epoxide reductase. Biochem Pharmacol. 1989 Apr 1;38(7):1115-20. [PubMed:2706010 ]
    4. Thijssen HH, Baars LG, Vervoort-Peters HT: Vitamin K 2,3-epoxide reductase: the basis for stereoselectivity of 4-hydroxycoumarin anticoagulant activity. Br J Pharmacol. 1988 Nov;95(3):675-82. [PubMed:3207986 ]
    5. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]

    PMID: 22685301

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