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Dabigatran etexilate

July 24, 2017
Common Name

Dabigatran etexilate Description

Dabigatran etexilate is an oral prodrug that is metabolized by a serum esterase to dabigatran. It is a synthetic, competitive and reversible direct thrombin inhibitor. Inhibition of thrombin disrupts the coagliation cascade and inhibits the formation of clots. Dabigatran etexilate may be used to decrease the risk of venous thromboembolic events in patients who have undergone total hip or knee replacement surgery, or to prevent stroke and systemic embolism in patients with atrial fibrillation, in whom anticoagliation therapy is indicated. Structure

MOLSDFPDBSMILESInChI

Synonyms

Value Source PradaxaKegg Dabigatran etexilic acidGenerator DabigatranHMDB Ethyl 3-[[[4-[[[(hexyloxyl)carbonyl]amino]iminomethyl]phenyl]amino]methyl]-1-methyl-1H-benzimidazol-5-yl]carbonyl](pyridin-2-yl)amino] propanoateHMDB Etexilate mesylate, dabigatranMeSH Etexilate, dabigatranMeSH BIBR 1048MeSH Mesylate, dabigatran etexilateMeSH N-((2-(((4-(Aminoiminomethyl)phenyl)amino)methyl)-1-methyl-1H-benzimidazol-5-yl)carbonyl)-N-2-pyridinyl-beta-alanineMeSH Dabigatran etexilate mesylateMeSH

Chemical Formlia

C34H41N7O5 Average Molecliar Weight

627.7332 Monoisotopic Molecliar Weight

627.316917457 IUPAC Name

ethyl 3-(1-{2-[({4-[amino({[(hexyloxy)carbonyl]imino})methyl]phenyl}amino)methyl]-1-methyl-1H-1,3-benzodiazol-5-yl}-N-(pyridin-2-yl)formamido)propanoate Traditional Name

dabigatran etexilate CAS Registry Number

211915-06-9 SMILES

CCCCCCOC(=O)N=C(N)C1=CC=C(NCC2=NC3=C(C=CC(=C3)C(=O)N(CCC(=O)OCC)C3=CC=CC=N3)N2C)C=C1

InChI Identifier

InChI=1S/C34H41N7O5/c1-4-6-7-10-21-46-34(44)39-32(35)24-12-15-26(16-13-24)37-23-30-38-27-22-25(14-17-28(27)40(30)3)33(43)41(20-18-31(42)45-5-2)29-11-8-9-19-36-29/h8-9,11-17,19,22,37H,4-7,10,18,20-21,23H2,1-3H3,(H2,35,39,44)

InChI Key

KSGXQBZTULBEEQ-UHFFFAOYSA-N Chemical Taxonomy Description

This compound belongs to the class of chemical entities known as benzimidazoles. These are organic compounds containing a benzene ring fused to an imidazole ring (five member ring containing a nitrogen atom, 4 carbon atoms, and two double bonds). Kingdom

Chemical entities Super Class

Organic compounds Class

Organoheterocyclic compounds Sub Class

Benzimidazoles Direct Parent

Benzimidazoles Alternative Parents

  • Phenylalkylamines
  • Aniline and substituted anilines
  • Secondary alkylarylamines
  • Pyridines and derivatives
  • N-substituted imidazoles
  • Imidolactams
  • Tertiary carboxylic acid amides
  • Heteroaromatic compounds
  • Amino acids and derivatives
  • Carboxylic acid esters
  • Organic carbonic acids and derivatives
  • Propargyl-type 1,3-dipolar organic compounds
  • Azacyclic compounds
  • Carboxamidines
  • Carboximidamides
  • Monocarboxylic acids and derivatives
  • Carbonyl compounds
  • Organic oxides
  • Organopnictogen compounds
  • Hydrocarbon derivatives

    • Substituents

  • Benzimidazole
  • Aniline or substituted anilines
  • Phenylalkylamine
  • Secondary aliphatic/aromatic amine
  • Aralkylamine
  • Monocyclic benzene moiety
  • N-substituted imidazole
  • Pyridine
  • Benzenoid
  • Imidolactam
  • Azole
  • Imidazole
  • Tertiary carboxylic acid amide
  • Heteroaromatic compound
  • Carboxylic acid ester
  • Carboxamide group
  • Carbonic acid derivative
  • Amino acid or derivatives
  • Monocarboxylic acid or derivatives
  • Amidine
  • Carboxylic acid amidine
  • Organic 1,3-dipolar compound
  • Carboxylic acid derivative
  • Azacycle
  • Secondary amine
  • Propargyl-type 1,3-dipolar organic compound
  • Carboximidamide
  • Organic oxygen compound
  • Amine
  • Organonitrogen compound
  • Carbonyl group
  • Organic nitrogen compound
  • Organooxygen compound
  • Organopnictogen compound
  • Organic oxide
  • Hydrocarbon derivative
  • Aromatic heteropolycyclic compound

    • Molecliar Framework

    Aromatic heteropolycyclic compounds External Descriptors

  • carboxylic ester (CHEBI:70746 )
  • carboxamidine (CHEBI:70746 )
  • beta-alanine derivative (CHEBI:70746 )
  • pyridines (CHEBI:70746 )
  • aromatic amide (CHEBI:70746 )
  • benzimidazoles (CHEBI:70746 )

    • Ontology Status

    Expected but not Quantified Origin

  • Drug

    • Biofunction

  • Anticoagliants
  • Antithrombotic Agents
  • Antithrombotics

    • Application

  • Pharmaceutical

    • Cellliar locations

  • Extracellliar
  • Membrane

    • Physical Properties State

    Solid Experimental Properties

    Property Value Reference Melting Point180 °CNot Available Boiling PointNot AvailableNot Available Water SolubilityNot AvailableNot Available LogP3.8Not Available

    Predicted Properties

    Property Value Source Water Solubility0.0047 mg/mLALOGPS logP5.17ALOGPS logP4.59ChemAxon logS-5.1ALOGPS pKa (Strongest Acidic)17.89ChemAxon pKa (Strongest Basic)3.87ChemAxon Physiological Charge0ChemAxon Hydrogen Acceptor Count8ChemAxon Hydrogen Donor Count2ChemAxon Polar Surface Area154.03 Å2ChemAxon Rotatable Bond Count17ChemAxon Refractivity176.43 m3·mol-1ChemAxon Polarizability71.11 Å3ChemAxon Number of Rings4ChemAxon Bioavailability0ChemAxon Rlie of FiveYesChemAxon Ghose FilterYesChemAxon Vebers RlieYesChemAxon MDDR-like RlieYesChemAxon

    Spectra Spectra

    Spectrum Type Description Splash Key LC-MS/MS

    LC-MS/MS Spectrum – , positivesplash10-00kk-0981100000-78856b63936cf67ebce2View in MoNA LC-MS/MS

    LC-MS/MS Spectrum – , positivesplash10-004r-0292116000-55b368cbe92da888e681View in MoNA 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

    Not Available Normal Concentrations

    Biofluid Status Value Age Sex Condition Reference Details BloodExpected but not Quantified Not AvailableNot AvailableTaking drug identified by DrugBank entry DB06695

  • 21059682

    • details UrineExpected but not Quantified Not AvailableNot AvailableTaking drug identified by DrugBank entry DB06695

  • 21059682

    • details

    Abnormal Concentrations

    Not Available Associated Disorders and Diseases Disease References

    None Associated OMIM IDs

    None External Links DrugBank ID

    DB06695 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

    4948999 KEGG Compound ID

    Not Available BioCyc ID

    Not Available BiGG ID

    Not Available Wikipedia Link

    Dabigatran NuGOwiki Link

    HMDB15641 Metagene Link

    HMDB15641 METLIN ID

    Not Available PubChem Compound

    213023 PDB ID

    Not Available ChEBI ID

    661520

    Product: Procaine

    References Synthesis Reference Not Available Material Safety Data Sheet (MSDS) Not Available General References
    1. Di Nisio M, Middeldorp S, Buller HR: Direct thrombin inhibitors. N Engl J Med. 2005 Sep 8;353(10):1028-40. [PubMed:16148288 ]
    2. Eriksson BI, Dahl OE, Buller HR, Hettiarachchi R, Rosencher N, Bravo ML, Ahnfelt L, Piovella F, Stangier J, Kalebo P, Reilly P: A new oral direct thrombin inhibitor, dabigatran etexilate, compared with enoxaparin for prevention of thromboembolic events following total hip or knee replacement: the BISTRO II randomized trial. J Thromb Haemost. 2005 Jan;3(1):103-11. [PubMed:15634273 ]
    3. Stangier J, Eriksson BI, Dahl OE, Ahnfelt L, Nehmiz G, Stahle H, Rathgen K, Svard R: Pharmacokinetic profile of the oral direct thrombin inhibitor dabigatran etexilate in healthy volunteers and patients undergoing total hip replacement. J Clin Pharmacol. 2005 May;45(5):555-63. [PubMed:15831779 ]
    4. Eriksson BI, Dahl OE, Rosencher N, Kurth AA, van Dijk CN, Frostick SP, Kalebo P, Christiansen AV, Hantel S, Hettiarachchi R, Schnee J, Buller HR: Oral dabigatran etexilate vs. subcutaneous enoxaparin for the prevention of venous thromboembolism after total knee replacement: the RE-MODEL randomized trial. J Thromb Haemost. 2007 Nov;5(11):2178-85. [PubMed:17764540 ]
    5. Eriksson BI, Dahl OE, Rosencher N, Kurth AA, van Dijk CN, Frostick SP, Prins MH, Hettiarachchi R, Hantel S, Schnee J, Buller HR: Dabigatran etexilate versus enoxaparin for prevention of venous thromboembolism after total hip replacement: a randomised, double-blind, non-inferiority trial. Lancet. 2007 Sep 15;370(9591):949-56. [PubMed:17869635 ]
    6. Ezekowitz MD, Reilly PA, Nehmiz G, Simmers TA, Nagarakanti R, Parcham-Azad K, Pedersen KE, Lionetti DA, Stangier J, Wallentin L: Dabigatran with or without concomitant aspirin compared with warfarin alone in patients with nonvalvular atrial fibrillation (PETRO Study). Am J Cardiol. 2007 Nov 1;100(9):1419-26. Epub 2007 Aug 17. [PubMed:17950801 ]
    7. Ginsberg JS, Davidson BL, Comp PC, Francis CW, Friedman RJ, Huo MH, Lieberman JR, Muntz JE, Raskob GE, Clements ML, Hantel S, Schnee JM, Caprini JA: Oral thrombin inhibitor dabigatran etexilate vs North American enoxaparin regimen for prevention of venous thromboembolism after knee arthroplasty surgery. J Arthroplasty. 2009 Jan;24(1):1-9. doi: 10.1016/j.arth.2008.01.132. Epub 2008 Apr 14. [PubMed:18534438 ]
    8. Wolowacz SE, Roskell NS, Plumb JM, Caprini JA, Eriksson BI: Efficacy and safety of dabigatran etexilate for the prevention of venous thromboembolism following total hip or knee arthroplasty. A meta-analysis. Thromb Haemost. 2009 Jan;101(1):77-85. [PubMed:19132192 ]
    9. Connolly SJ, Ezekowitz MD, Yusuf S, Eikelboom J, Oldgren J, Parekh A, Pogue J, Reilly PA, Themeles E, Varrone J, Wang S, Alings M, Xavier D, Zhu J, Diaz R, Lewis BS, Darius H, Diener HC, Joyner CD, Wallentin L: Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med. 2009 Sep 17;361(12):1139-51. doi: 10.1056/NEJMoa0905561. Epub 2009 Aug 30. [PubMed:19717844 ]
    10. Bauer KA: New oral anticoagulants in development: potential for improved safety profiles. Rev Neurol Dis. 2010;7(1):1-8. [PubMed:20410856 ]
    11. Scaglione F: New oral anticoagulants: comparative pharmacology with vitamin K antagonists. Clin Pharmacokinet. 2013 Feb;52(2):69-82. doi: 10.1007/s40262-012-0030-9. [PubMed:23292752 ]
    12. European Medicines Agency [Link]
    13. Abrams P and Marzella N: Dabigatran (Rendix): A Promising New Oral Direct Thrombin Inhibitor. Drug Forecast. 2007;32(5):271-5. [Link]

    Transporters

    General function:
    Involved in ATP binding
    Specific function:
    Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells
    Gene Name:
    ABCB1
    Uniprot ID:
    P08183
    Molecular weight:
    141477.3
    References
    1. Galanis T, Thomson L, Palladino M, Merli GJ: New oral anticoagulants. J Thromb Thrombolysis. 2011 Apr;31(3):310-20. doi: 10.1007/s11239-011-0559-8. [PubMed:21327511 ]

    PMID: 15788769

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