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Showing metabocard for Ximelagatran (HMDB0015603)

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IdentificationTaxonomyOntologyPhysical propertiesSpectraBiological propertiesConcentrationsLinksReferencesenzymes (1) Show 1 proteinXML
enzymes (1) Show 1 protein
Record Information
Version4.0
StatusExpected but not Quantified
Creation Date2012-09-06 15:16:52 UTC
Update Date2020-02-26 21:41:55 UTC
HMDB IDHMDB0015603
Secondary Accession Numbers
  • HMDB15603
Metabolite Identification
Common NameXimelagatran
DescriptionXimelagatran, also known as exanta or H 376-95, belongs to the class of organic compounds known as dipeptides. These are organic compounds containing a sequence of exactly two alpha-amino acids joined by a peptide bond. Ximelagatran (Ximelagatran or Exarta, H 376/95) is an anticoagulant that has been investigated extensively as a replacement for warfarin that would overcome the problematic dietary, drug interaction, and monitoring issues associated with warfarin therapy. Ximelagatran is a drug which is used for the treatment of acute deep vein thrombosis. Ximelagatran is a very strong basic compound (based on its pKa). In humans, ximelagatran is involved in ximelagatran action pathway. Ximelagatran is a prodrug, and hence, it requires in vivo conversion to the active agent, melagatran. The activation of ximelagatran is produced in the liver and many other tissues mainly by reactions of dealkylation and dehydroxylation. Ximelagatran is an anticoagulant intended to become a replacement for warfarin by overcoming the dietary restrictions, drug interaction, and monitoring issues associated with the former. Its effect is solely related to the inhibition of thrombin. Ximelagatran was the first member of the drug class of direct thrombin inhibitors that can be taken orally.
Structure
Data?1582753315
MOLSDFPDBSMILESInChI
Synonyms
ValueSource
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
Ximelagatran (oxime form)ChEBI
XimelagatranumChEBI
Ethyl 2-[[(1R)-1-cyclohexyl-2- [(2S)-2-[[4-(n'-hydroxycarbamimidoyl) phenyl]methylcarbamoyl]azetidin-1-yl]- 2-oxo-ethyl]amino]acetic acidGenerator
XI-melagatranHMDB
Glycine, N-((1R)1-cyclohexyl-2-((2S)-((((4-(amino(hydroxyimino)methyl)phenyl)methyl)amino)carbonyl)-1-azetidinyl)2-oxoethyl)-ethyl esterHMDB
Glycine, N-((1)1-cyclohexyl-2-((2)-((((4-(amino(hydroxyimino)methyl)phenyl)methyl)amino)carbonyl)-1-azetidinyl)2-oxoethyl)-ethyl esterHMDB
Chemical FormulaC24H35N5O5
Average Molecular Weight473.5652
Monoisotopic Molecular Weight473.263819255
IUPAC Nameethyl 2-{[(1R)-1-cyclohexyl-2-[(2S)-2-[({4-[(Z)-N'-hydroxycarbamimidoyl]phenyl}methyl)carbamoyl]azetidin-1-yl]-2-oxoethyl]amino}acetate
Traditional Nameximelagatran
CAS Registry Number192939-46-1
SMILES
CCOC(=O)CN[C@@H](C(=O)N1CC[C@H]1C(=O)NCC1=CC=C(C=C1)C(\N)=N\O)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 KeyZXIBCJHYVWYIKI-PZJWPPBQSA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as dipeptides. These are organic compounds containing a sequence of exactly two alpha-amino acids joined by a peptide bond.
KingdomOrganic compounds
Super ClassOrganic acids and derivatives
ClassCarboxylic acids and derivatives
Sub ClassAmino acids, peptides, and analogues
Direct ParentDipeptides
Alternative Parents
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
Molecular FrameworkAromatic heteromonocyclic compounds
External Descriptors
Ontology
Disposition

Biological location:

Process

Naturally occurring process:

Role

Industrial application:

Physical Properties
StateSolid
Experimental Properties
PropertyValueReference
Melting PointNot AvailableNot Available
Boiling PointNot AvailableNot Available
Water Solubility0.084 g/LNot Available
LogPNot AvailableNot Available
Predicted Properties
PropertyValueSource
Water Solubility0.084 g/LALOGPS
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 ŲChemAxon
Rotatable Bond Count11ChemAxon
Refractivity126.57 m³·mol⁻¹ChemAxon
Polarizability52.15 ųChemAxon
Number of Rings3ChemAxon
BioavailabilityYesChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectrum TypeDescriptionSplash KeyView
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-004j-4982400000-32fe628a565ad95d34f7Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-03ka-0910600000-44563426df349abe783aSpectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-01ot-1900000000-993c6a2f4f07b4664b53Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0002-2900000000-7463f581ac8e0bfad363Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-010r-1091600000-caf9b25e0e59704abc3dSpectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0i6r-1390100000-fa8587138131e92bfa4bSpectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0f6t-9780000000-e48b26348d984d96c2caSpectrum
Biological Properties
Cellular Locations
  • Extracellular
  • Membrane
Biospecimen Locations
  • Blood
  • Urine
Tissue LocationsNot Available
Pathways
Normal Concentrations
BiospecimenStatusValueAgeSexConditionReferenceDetails
BloodExpected but not QuantifiedNot QuantifiedNot AvailableNot AvailableTaking drug identified by DrugBank entry DB04898 details
UrineExpected but not QuantifiedNot QuantifiedNot AvailableNot AvailableTaking drug identified by DrugBank entry DB04898 details
Abnormal Concentrations
Not Available
Associated Disorders and Diseases
Disease ReferencesNone
Associated OMIM IDsNone
DrugBank IDDB04898
Phenol Explorer Compound IDNot Available
FooDB IDNot Available
KNApSAcK IDNot Available
Chemspider ID7848559
KEGG Compound IDNot Available
BioCyc IDNot Available
BiGG IDNot Available
Wikipedia LinkXimelagatran
METLIN IDNot Available
PubChem Compound656635
PDB IDNot Available
ChEBI ID65172
Food Biomarker OntologyNot Available
VMH IDNot Available
MarkerDB ID
References
Synthesis ReferenceNot 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

Enzyme Details
1. Cytochrome P450 2C9
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 ]