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Ximelagatran

July 24, 2017
Common Name

Ximelagatran Description

Ximelagatran (Exanta or Exarta, H 376/95) is an anticoagliant that has been investigated extensively as a replacement for warfarin that wolid overcome the problematic dietary, drug interaction, and monitoring issues associated with warfarin therapy. In 2006, its manufacturer AstraZeneca announced that it wolid not attempt to market ximelagatran after reports of hepatotoxicity (liver damage) during trials, and to discontinue its distribution in countries where the drug had been approved. Structure

MOLSDF3D-SDFPDBSMILESInChI View 3D Structure

Synonyms

Value Source Ethyl 2-[[(1R)-1-cyclohexyl-2- [(2S)-2-[[4-(n'-hydroxycarbamimidoyl) phenyl]methylcarbamoyl]azetidin-1-yl]- 2-oxo-ethyl]amino]acetateChEBI ExantaChEBI ExartaChEBI H 376-95ChEBI H 376/95ChEBI H 37695ChEBI XimelagatranumChEBI Ethyl 2-[[(1R)-1-cyclohexyl-2- [(2S)-2-[[4-(n'-hydroxycarbamimidoyl) phenyl]methylcarbamoyl]azetidin-1-yl]- 2-oxo-ethyl]amino]acetic acidGenerator XI-melagatranMeSH Glycine, N-((1R)1-cyclohexyl-2-((2S)-((((4-(amino(hydroxyimino)methyl)phenyl)methyl)amino)carbonyl)-1-azetidinyl)2-oxoethyl)-ethyl esterMeSH Glycine, N-((1)1-cyclohexyl-2-((2)-((((4-(amino(hydroxyimino)methyl)phenyl)methyl)amino)carbonyl)-1-azetidinyl)2-oxoethyl)-ethyl esterMeSH

Chemical Formlia

C24H35N5O5 Average Molecliar Weight

473.5652 Monoisotopic Molecliar Weight

473.263819255 IUPAC Name

ethyl 2-{[(1R)-1-cyclohexyl-2-[(2S)-2-[({4-[(Z)-N-hydroxycarbamimidoyl]phenyl}methyl)carbamoyl]azetidin-1-yl]-2-oxoethyl]amino}acetate Traditional Name

ximelagatran CAS Registry Number

192939-46-1 SMILES

CCOC(=O)CN[C@@H](C(=O)N1CC[C@H]1C(=O)NCC1=CC=C(C=C1)C(N)=NO)C1CCCCC1

InChI Identifier

InChI=1S/C24H35N5O5/c1-2-34-20(30)15-26-21(17-6-4-3-5-7-17)24(32)29-13-12-19(29)23(31)27-14-16-8-10-18(11-9-16)22(25)28-33/h8-11,17,19,21,26,33H,2-7,12-15H2,1H3,(H2,25,28)(H,27,31)/t19-,21+/m0/s1

InChI Key

ZXIBCJHYVWYIKI-PZJWPPBQSA-N Chemical Taxonomy Description

This compound belongs to the class of chemical entities known as dipeptides. These are organic compounds containing a sequence of exactly two alpha-amino acids joined by a peptide bond. Kingdom

Chemical entities Super Class

Organic compounds Class

Organic acids and derivatives Sub Class

Carboxylic acids and derivatives Direct Parent

Dipeptides Alternative Parents

  • Alpha amino acid esters
  • Alpha amino acid amides
  • Benzene and substituted derivatives
  • Tertiary carboxylic acid amides
  • Amidoximes
  • Secondary carboxylic acid amides
  • Carboxylic acid esters
  • Azetidines
  • Monocarboxylic acids and derivatives
  • Dialkylamines
  • Azacyclic compounds
  • Organopnictogen compounds
  • Organic oxides
  • Hydrocarbon derivatives
  • Carbonyl compounds

    • Substituents

  • Alpha-dipeptide
  • Alpha-amino acid ester
  • Alpha-amino acid amide
  • Alpha-amino acid or derivatives
  • Monocyclic benzene moiety
  • Benzenoid
  • Amidoxime
  • Tertiary carboxylic acid amide
  • Amino acid or derivatives
  • Azetidine
  • Carboxamide group
  • Secondary carboxylic acid amide
  • Carboxylic acid ester
  • Amidine
  • Azacycle
  • Organoheterocyclic compound
  • Secondary amine
  • Secondary aliphatic amine
  • Monocarboxylic acid or derivatives
  • Carbonyl group
  • Organic oxygen compound
  • Hydrocarbon derivative
  • Organopnictogen compound
  • Organic nitrogen compound
  • Amine
  • Organic oxide
  • Organonitrogen compound
  • Organooxygen compound
  • Aromatic heteromonocyclic compound

    • Molecliar Framework

    Aromatic heteromonocyclic compounds External Descriptors

  • ethyl ester (CHEBI:65172 )
  • secondary amino compound (CHEBI:65172 )
  • carboxamide (CHEBI:65172 )
  • azetidines (CHEBI:65172 )
  • amidoxime (CHEBI:65172 )

    • Ontology Status

    Expected but not Quantified Origin

  • Drug

    • Biofunction

  • Anticoagliants
  • Antithrombotic Agents

    • Application

  • Pharmaceutical

    • Cellliar locations

  • Extracellliar
  • Membrane

    • Physical Properties State

    Solid Experimental Properties

    Property Value Reference Melting PointNot AvailableNot Available Boiling PointNot AvailableNot Available Water Solubility8.45e-02 g/LNot Available LogPNot AvailableNot Available

    Predicted Properties

    Property Value Source Water Solubility0.085 mg/mLALOGPS logP1.35ALOGPS logP0.87ChemAxon logS-3.8ALOGPS pKa (Strongest Acidic)9.64ChemAxon pKa (Strongest Basic)5.48ChemAxon Physiological Charge0ChemAxon Hydrogen Acceptor Count7ChemAxon Hydrogen Donor Count4ChemAxon Polar Surface Area146.35 Å2ChemAxon Rotatable Bond Count11ChemAxon Refractivity126.57 m3·mol-1ChemAxon Polarizability52.15 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 Ximelagatran PathwaySMP00279Not Available

    Normal Concentrations

    Biofluid Status Value Age Sex Condition Reference Details BloodExpected but not Quantified Not AvailableNot AvailableTaking drug identified by DrugBank entry DB04898

  • 21059682

    • details UrineExpected but not Quantified Not AvailableNot AvailableTaking drug identified by DrugBank entry DB04898

  • 21059682

    • details

    Abnormal Concentrations

    Not Available Associated Disorders and Diseases Disease References

    None Associated OMIM IDs

    None External Links DrugBank ID

    DB04898 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

    7848559 KEGG Compound ID

    Not Available BioCyc ID

    Not Available BiGG ID

    Not Available Wikipedia Link

    Ximelagatran NuGOwiki Link

    HMDB15603 Metagene Link

    HMDB15603 METLIN ID

    Not Available PubChem Compound

    656635 PDB ID

    Not Available ChEBI ID

    65172

    Product: Mc-MMAE

    References Synthesis Reference Not Available Material Safety Data Sheet (MSDS) Not Available General References
    1. Eriksson H, Wahlander K, Gustafsson D, Welin LT, Frison L, Schulman S: A randomized, controlled, dose-guiding study of the oral direct thrombin inhibitor ximelagatran compared with standard therapy for the treatment of acute deep vein thrombosis: THRIVE I. J Thromb Haemost. 2003 Jan;1(1):41-7. [PubMed:12871538 ]
    2. Francis CW, Berkowitz SD, Comp PC, Lieberman JR, Ginsberg JS, Paiement G, Peters GR, Roth AW, McElhattan J, Colwell CW Jr: Comparison of ximelagatran with warfarin for the prevention of venous thromboembolism after total knee replacement. N Engl J Med. 2003 Oct 30;349(18):1703-12. [PubMed:14585938 ]
    3. Weitz JI: New anticoagulants for treatment of venous thromboembolism. Circulation. 2004 Aug 31;110(9 Suppl 1):I19-26. [PubMed:15339877 ]
    4. Bergqvist D, Solhaug JH, Holmdahl L, Eriksson UG, Andersson M, Boberg B, Ogren M: Pharmacokinetics, preliminary efficacy and safety of subcutaneous melagatran and oral ximelagatran : a multicentre study of thromboprophylaxis in elective abdominal surgery. Clin Drug Investig. 2004;24(3):127-36. [PubMed:17516699 ]
    5. Koscielny J, Kiesewetter H, Jorg I, Harenberg J: Ximelagatran for treatment and prophylaxis of recurrent events in deep vein thrombosis. Clin Appl Thromb Hemost. 2007 Jul;13(3):299-307. [PubMed:17636192 ]

    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 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. 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 ]

    PMID: 11934585

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