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Acenocoumarol

July 24, 2017
Common Name

Acenocoumarol Description

Acenocoumarol is a coumarin derivative used as an anticoagliant. Coumarin derivatives inhibit the reduction of vitamin K by vitamin K reductase. This prevents carboxylation of vitamin K-dependent clotting factors, II, VII, XI and X, and interferes with coagliation. Hematocrit, hemoglobin, international normalized ratio and liver panel sholid be monitored. Patients on acenocoumarol are prohibited from giving blood. Structure

MOLSDF3D-SDFPDBSMILESInChI View 3D Structure

Synonyms

Value Source 3-(alpha-(4'-Nitrophenyl)-beta-acetylethyl)-4-hydroxycoumarinChEBI 3-(alpha-(P-Nitrophenol)-beta-acetylethyl)-4-hydroxycoumarinChEBI 3-(alpha-Acetonyl-4-nitrobenzyl)-4-hydroxycoumarinChEBI 3-(alpha-Acetonyl-P-nitrobenzyl)-4-hydroxycoumarinChEBI 3-(alpha-P-Nitrophenyl-beta-acetylethyl)-4-hydroxycoumarinChEBI 4-Hydroxy-3-(1-(4-nitrophenyl)-3-oxobutyl)-2H-1-benzopyran-2-oneChEBI 4-Hydroxy-3-[1-(4-nitrophenyl)-3-oxobutyl]-2H-chromen-2-oneChEBI AcenocoumarinChEBI AcenocoumarolumChEBI AcenocumarolChEBI AcenocumaroloChEBI AcenokumarinChEBI NicoumaloneChEBI NicumalonChEBI Nitrophenylacetylethyl-4-hydroxycoumarineChEBI NitrovarfarianChEBI NitrowarfarinChEBI 3-(a-(4'-Nitrophenyl)-b-acetylethyl)-4-hydroxycoumarinGenerator 3-(α-(4'-nitrophenyl)-β-acetylethyl)-4-hydroxycoumarinGenerator 3-(a-(P-Nitrophenol)-b-acetylethyl)-4-hydroxycoumarinGenerator 3-(α-(P-nitrophenol)-β-acetylethyl)-4-hydroxycoumarinGenerator 3-(a-Acetonyl-4-nitrobenzyl)-4-hydroxycoumarinGenerator 3-(α-acetonyl-4-nitrobenzyl)-4-hydroxycoumarinGenerator 3-(a-Acetonyl-P-nitrobenzyl)-4-hydroxycoumarinGenerator 3-(α-acetonyl-P-nitrobenzyl)-4-hydroxycoumarinGenerator 3-(a-P-Nitrophenyl-b-acetylethyl)-4-hydroxycoumarinGenerator 3-(α-P-nitrophenyl-β-acetylethyl)-4-hydroxycoumarinGenerator Ciba-geigy brand OF acenocoumarolMeSH Mini sintromMeSH Novartis brand OF acenocoumarolMeSH SinkumarMeSH SyncoumarMeSH SynthromMeSH Acenocoumarol alliance brandMeSH Acenocoumarol novartis brandMeSH Alliance brand OF acenocoumarolMeSH Ciba geigy brand OF acenocoumarolMeSH MiniSintromMeSH SyncumarMeSH Acenocoumarol ciba-geigy brandMeSH Mini-sintromMeSH SinthromeMeSH SintromMeSH

Chemical Formlia

C19H15NO6 Average Molecliar Weight

353.3255 Monoisotopic Molecliar Weight

353.089937217 IUPAC Name

4-hydroxy-3-[1-(4-nitrophenyl)-3-oxobutyl]-2H-chromen-2-one Traditional Name

acenocumarolo CAS Registry Number

152-72-7 SMILES

CC(=O)CC(C1=CC=C(C=C1)[N+]([O-])=O)C1=C(O)C2=CC=CC=C2OC1=O

InChI Identifier

InChI=1S/C19H15NO6/c1-11(21)10-15(12-6-8-13(9-7-12)20(24)25)17-18(22)14-4-2-3-5-16(14)26-19(17)23/h2-9,15,22H,10H2,1H3

InChI Key

VABCILAOYCMVPS-UHFFFAOYSA-N Chemical Taxonomy Description

This compound 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. Kingdom

Organic compounds Super Class

Phenylpropanoids and polyketides Class

Coumarins and derivatives Sub Class

Hydroxycoumarins Direct Parent

4-hydroxycoumarins Alternative Parents

  • 1-benzopyrans
  • Nitrobenzenes
  • Nitroaromatic compounds
  • Pyranones and derivatives
  • Vinylogous acids
  • Heteroaromatic compounds
  • Lactones
  • Ketones
  • Propargyl-type 1,3-dipolar organic compounds
  • Oxacyclic compounds
  • Organic oxoazanium compounds
  • Organopnictogen compounds
  • Organonitrogen compounds
  • Organic oxides
  • Hydrocarbon derivatives

    • Substituents

  • 4-hydroxycoumarin
  • Benzopyran
  • 1-benzopyran
  • Nitrobenzene
  • Nitroaromatic compound
  • Pyranone
  • Monocyclic benzene moiety
  • Pyran
  • Benzenoid
  • Heteroaromatic compound
  • Vinylogous acid
  • Ketone
  • Lactone
  • C-nitro compound
  • Organic nitro compound
  • Oxacycle
  • Organic oxoazanium
  • Organoheterocyclic compound
  • Allyl-type 1,3-dipolar organic compound
  • Propargyl-type 1,3-dipolar organic compound
  • Organic 1,3-dipolar compound
  • Organopnictogen compound
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organonitrogen compound
  • Organic oxide
  • Organic oxygen compound
  • Organic nitrogen compound
  • Carbonyl group
  • Aromatic heteropolycyclic compound

    • Molecliar Framework

    Aromatic heteropolycyclic compounds External Descriptors

  • C-nitro compound (CHEBI:53766 )
  • methyl ketone (CHEBI:53766 )
  • hydroxycoumarin (CHEBI:53766 )

    • Ontology Status

    Expected but not Quantified Origin

  • Drug

    • Biofunction

  • Anticoagliants
  • Coumarin and Indandione Derivatives

    • Application

  • Pharmaceutical

    • Cellliar locations

  • Extracellliar
  • Membrane

    • Physical Properties State

    Solid Experimental Properties

    Property Value Reference Melting Point197 °CNot Available Boiling PointNot AvailableNot Available Water Solubility1.06e-02 g/LNot Available LogP1.98SANGSTER (1994)

    Predicted Properties

    Property Value Source Water Solubility0.011 mg/mLALOGPS logP2.53ALOGPS logP2.68ChemAxon logS-4.5ALOGPS pKa (Strongest Acidic)5.79ChemAxon pKa (Strongest Basic)-6.8ChemAxon Physiological Charge-1ChemAxon Hydrogen Acceptor Count5ChemAxon Hydrogen Donor Count1ChemAxon Polar Surface Area109.42 Å2ChemAxon Rotatable Bond Count5ChemAxon Refractivity94.18 m3·mol-1ChemAxon Polarizability34.35 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 Acenocoumarol PathwaySMP00269Not Available

    Normal Concentrations

    Biofluid Status Value Age Sex Condition Reference Details BloodExpected but not Quantified Not AvailableNot AvailableTaking drug identified by DrugBank entry DB01418

  • 21059682

    • details UrineExpected but not Quantified Not AvailableNot AvailableTaking drug identified by DrugBank entry DB01418

  • 21059682

    • details

    Abnormal Concentrations

    Not Available Predicted Concentrations

    Biofluid Value Original age Original sex Original condition Comments Blood0-3 uMAdlit (>18 years old)BothNormalPredicted based on drug qualities Blood0-1 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

    DB01418 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

    10443441 KEGG Compound ID

    Not Available BioCyc ID

    Not Available BiGG ID

    Not Available Wikipedia Link

    Acenocoumarol NuGOwiki Link

    HMDB15487 Metagene Link

    HMDB15487 METLIN ID

    Not Available PubChem Compound

    54676537 PDB ID

    Not Available ChEBI ID

    53766

    Product: VER-49010

    References Synthesis Reference Not Available Material Safety Data Sheet (MSDS) Not Available General References
    1. Ufer M: Comparative pharmacokinetics of vitamin K antagonists: warfarin, phenprocoumon and acenocoumarol. Clin Pharmacokinet. 2005;44(12):1227-46. [PubMed:16372822 ]
    2. Montes R, Ruiz de Gaona E, Martinez-Gonzalez MA, Alberca I, Hermida J: The c.-1639G > A polymorphism of the VKORC1 gene is a major determinant of the response to acenocoumarol in anticoagulated patients. Br J Haematol. 2006 Apr;133(2):183-7. [PubMed:16611310 ]
    3. Girard P, Nony P, Erhardtsen E, Delair S, Ffrench P, Dechavanne M, Boissel JP: Population pharmacokinetics of recombinant factor VIIa in volunteers anticoagulated with acenocoumarol. Thromb Haemost. 1998 Jul;80(1):109-13. [PubMed:9684795 ]
    4. Cesar JM, Garcia-Avello A, Navarro JL, Herraez MV: Aging and oral anticoagulant therapy using acenocoumarol. Blood Coagul Fibrinolysis. 2004 Oct;15(8):673-6. [PubMed:15613922 ]
    5. Lengyel M: [Warfarin or acenocoumarol is better in the anticoagulant treatment of chronic atrial fibrillation?]. Orv Hetil. 2004 Dec 26;145(52):2619-21. [PubMed:15724697 ]

    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. Ufer M: Comparative pharmacokinetics of vitamin K antagonists: warfarin, phenprocoumon and acenocoumarol. Clin Pharmacokinet. 2005;44(12):1227-46. [PubMed:16372822 ]
    2. Morales-Molina JA, Arrebola MA, Robles PA, Mangana JC: Possible interaction between topical terbinafine and acenocoumarol. Ann Pharmacother. 2009 Nov;43(11):1911-2. doi: 10.1345/aph.1M299. Epub 2009 Oct 20. [PubMed:19843835 ]
    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. Stehle S, Kirchheiner J, Lazar A, Fuhr U: Pharmacogenetics of oral anticoagulants: a basis for dose individualization. Clin Pharmacokinet. 2008;47(9):565-94. [PubMed:18698879 ]
    3. Bodin L, Verstuyft C, Tregouet DA, Robert A, Dubert L, Funck-Brentano C, Jaillon P, Beaune P, Laurent-Puig P, Becquemont L, Loriot MA: Cytochrome P450 2C9 (CYP2C9) and vitamin K epoxide reductase (VKORC1) genotypes as determinants of acenocoumarol sensitivity. Blood. 2005 Jul 1;106(1):135-40. Epub 2005 Mar 24. [PubMed:15790782 ]
    4. Gonzalez-Conejero R, Corral J, Roldan V, Ferrer F, Sanchez-Serrano I, Sanchez-Blanco JJ, Marin F, Vicente V: The genetic interaction between VKORC1 c1173t and calumenin a29809g modulates the anticoagulant response of acenocoumarol. J Thromb Haemost. 2007 Aug;5(8):1701-6. Epub 2007 May 21. [PubMed:17596133 ]
    5. Montes R, Ruiz de Gaona E, Martinez-Gonzalez MA, Alberca I, Hermida J: The c.-1639G > A polymorphism of the VKORC1 gene is a major determinant of the response to acenocoumarol in anticoagulated patients. Br J Haematol. 2006 Apr;133(2):183-7. [PubMed:16611310 ]
    6. Rettie AE, Farin FM, Beri NG, Srinouanprachanh SL, Rieder MJ, Thijssen HH: A case study of acenocoumarol sensitivity and genotype-phenotype discordancy explained by combinations of polymorphisms in VKORC1 and CYP2C9. Br J Clin Pharmacol. 2006 Nov;62(5):617-20. Epub 2006 Jul 21. [PubMed:16869821 ]
    7. Schalekamp T, Brasse BP, Roijers JF, Chahid Y, van Geest-Daalderop JH, de Vries-Goldschmeding H, van Wijk EM, Egberts AC, de Boer A: VKORC1 and CYP2C9 genotypes and acenocoumarol anticoagulation status: interaction between both genotypes affects overanticoagulation. Clin Pharmacol Ther. 2006 Jul;80(1):13-22. [PubMed:16815313 ]
    8. 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:
    Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and imipramine.
    Gene Name:
    CYP2C19
    Uniprot ID:
    P33261
    Molecular weight:
    55944.565
    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 ]
    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. Most active in catalyzing 2-hydroxylation. Caffeine is metabolized primarily by cytochrome CYP1A2 in the liver through an initial N3-demethylation. Also acts in the metabolism of aflatoxin B1 and acetaminophen. Participates in the bioactivation of carcinogenic aromatic and heterocyclic amines. Catalizes the N-hydroxylation of heterocyclic amines and the O-deethylation of phenacetin.
    Gene Name:
    CYP1A2
    Uniprot ID:
    P05177
    Molecular weight:
    58406.915
    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 ]
    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. 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. Bodin L, Verstuyft C, Tregouet DA, Robert A, Dubert L, Funck-Brentano C, Jaillon P, Beaune P, Laurent-Puig P, Becquemont L, Loriot MA: Cytochrome P450 2C9 (CYP2C9) and vitamin K epoxide reductase (VKORC1) genotypes as determinants of acenocoumarol sensitivity. Blood. 2005 Jul 1;106(1):135-40. Epub 2005 Mar 24. [PubMed:15790782 ]
    3. Gonzalez-Conejero R, Corral J, Roldan V, Ferrer F, Sanchez-Serrano I, Sanchez-Blanco JJ, Marin F, Vicente V: The genetic interaction between VKORC1 c1173t and calumenin a29809g modulates the anticoagulant response of acenocoumarol. J Thromb Haemost. 2007 Aug;5(8):1701-6. Epub 2007 May 21. [PubMed:17596133 ]
    4. Montes R, Ruiz de Gaona E, Martinez-Gonzalez MA, Alberca I, Hermida J: The c.-1639G > A polymorphism of the VKORC1 gene is a major determinant of the response to acenocoumarol in anticoagulated patients. Br J Haematol. 2006 Apr;133(2):183-7. [PubMed:16611310 ]
    5. Rettie AE, Farin FM, Beri NG, Srinouanprachanh SL, Rieder MJ, Thijssen HH: A case study of acenocoumarol sensitivity and genotype-phenotype discordancy explained by combinations of polymorphisms in VKORC1 and CYP2C9. Br J Clin Pharmacol. 2006 Nov;62(5):617-20. Epub 2006 Jul 21. [PubMed:16869821 ]
    6. Schalekamp T, Brasse BP, Roijers JF, Chahid Y, van Geest-Daalderop JH, de Vries-Goldschmeding H, van Wijk EM, Egberts AC, de Boer A: VKORC1 and CYP2C9 genotypes and acenocoumarol anticoagulation status: interaction between both genotypes affects overanticoagulation. Clin Pharmacol Ther. 2006 Jul;80(1):13-22. [PubMed:16815313 ]
    7. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]

    PMID: 28231433

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