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Record Information
Version3.6
Creation Date2006-05-22 15:12:25 UTC
Update Date2016-02-11 01:07:01 UTC
HMDB IDHMDB05011
Secondary Accession NumbersNone
Metabolite Identification
Common NameClopidogrel
DescriptionClopidogrel is a potent oral antiplatelet agent often used in the treatment of coronary artery disease, peripheral vascular disease, and cerebrovascular disease. It is marketed by Bristol-Myers Squibb and Sanofi-Aventis under the trade name Plavix. -- Wikipedia; Clopidogrel is a potent oral antiplatelet agent often used in the treatment of coronary artery disease, peripheral vascular disease, and cerebrovascular disease. It is marketed by Bristol-Myers Squibb and Sanofi-Aventis under the trade name Plavix. It is also marketed in the generic form by Apotex, a large Canadian generic pharmaceutical company, though an injunction to withhold further shipments of their form is in effect while patent issues are dealt with. In 2005 it was the world's second highest selling pharmaceutical with sales of US$5.9 billion.
Structure
Thumb
Synonyms
ValueSource
(+)-ClopidogrelChEBI
ClopidogrelumChEBI
(+)-(S)-ClopidogrelHMDB
(S)-ClopidogrelHMDB
Clopidogrel bisulfateHMDB
Clopidogrel bisulphateHMDB
IsocoverHMDB
PlavixHMDB
Chemical FormulaC16H16ClNO2S
Average Molecular Weight321.822
Monoisotopic Molecular Weight321.059027158
IUPAC Namemethyl (2S)-2-(2-chlorophenyl)-2-{4H,5H,6H,7H-thieno[3,2-c]pyridin-5-yl}acetate
Traditional Nameclopidogrel
CAS Registry Number113665-84-2
SMILES
COC(=O)[C@@H](N1CCC2=C(C1)C=CS2)C1=CC=CC=C1Cl
InChI Identifier
InChI=1S/C16H16ClNO2S/c1-20-16(19)15(12-4-2-3-5-13(12)17)18-8-6-14-11(10-18)7-9-21-14/h2-5,7,9,15H,6,8,10H2,1H3/t15-/m0/s1
InChI KeyInChIKey=GKTWGGQPFAXNFI-HNNXBMFYSA-N
Chemical Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as alpha amino acid esters. These are ester derivatives of alpha amino acids.
KingdomOrganic compounds
Super ClassOrganic acids and derivatives
ClassCarboxylic acids and derivatives
Sub ClassAmino acids, peptides, and analogues
Direct ParentAlpha amino acid esters
Alternative Parents
Substituents
  • Alpha-amino acid ester
  • Phenylacetate
  • Thienopyridine
  • Aralkylamine
  • Halobenzene
  • Chlorobenzene
  • Benzenoid
  • Pyridine
  • Monocyclic benzene moiety
  • Aryl halide
  • Aryl chloride
  • Heteroaromatic compound
  • Methyl ester
  • Thiophene
  • Tertiary aliphatic amine
  • Tertiary amine
  • Carboxylic acid ester
  • Azacycle
  • Organoheterocyclic compound
  • Monocarboxylic acid or derivatives
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organonitrogen compound
  • Organochloride
  • Organohalogen compound
  • Carbonyl group
  • Amine
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors
Ontology
StatusExpected but not Quantified
Origin
  • Drug
BiofunctionNot Available
ApplicationNot Available
Cellular locations
  • Membrane (predicted from logP)
Physical Properties
StateSolid
Experimental Properties
PropertyValueReference
Melting PointNot AvailableNot Available
Boiling PointNot AvailableNot Available
Water SolubilityNot AvailableNot Available
LogPNot AvailableNot Available
Predicted Properties
PropertyValueSource
Water Solubility0.012 mg/mLALOGPS
logP3.84ALOGPS
logP4.03ChemAxon
logS-4.4ALOGPS
pKa (Strongest Basic)5.14ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area29.54 Å2ChemAxon
Rotatable Bond Count4ChemAxon
Refractivity84.93 m3·mol-1ChemAxon
Polarizability33.19 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash Key
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, PositiveNot Available
Biological Properties
Cellular Locations
  • Membrane (predicted from logP)
Biofluid LocationsNot Available
Tissue Location
  • Liver
  • Platelet
Pathways
NameSMPDB LinkKEGG Link
Clopidogrel Metabolism PathwaySMP00610Not Available
Clopidogrel PathwaySMP00260Not Available
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
Associated Disorders and Diseases
Disease ReferencesNone
Associated OMIM IDsNone
DrugBank IDNot Available
DrugBank Metabolite IDNot Available
Phenol Explorer Compound IDNot Available
Phenol Explorer Metabolite IDNot Available
FoodDB IDFDB023584
KNApSAcK IDNot Available
Chemspider ID54632
KEGG Compound IDNot Available
BioCyc IDNot Available
BiGG IDNot Available
Wikipedia LinkClopidogrel
NuGOwiki LinkHMDB05011
Metagene LinkHMDB05011
METLIN ID3965
PubChem Compound60606
PDB IDCGE
ChEBI ID37941
References
Synthesis ReferenceBousquet, Andre; Musolino, Andree. Hydroxyacetic ester derivatives, namely (R)-methyl 2-(sulfonyloxy)-2-(chlorophenyl)acetates, preparation method, and use as synthesis intermediates for clopidogrel. PCT Int. Appl. (1999), 35 p
Material Safety Data Sheet (MSDS)Not Available
General References
  1. Eikelboom JW, Hankey GJ, Thom J, Claxton A, Yi Q, Gilmore G, Staton J, Barden A, Norman PE: Enhanced antiplatelet effect of clopidogrel in patients whose platelets are least inhibited by aspirin: a randomized crossover trial. J Thromb Haemost. 2005 Dec;3(12):2649-55. [16359503 ]
  2. Contreres JO, Dupuy E, Job B, Habib A, Bryckaert M, Rosa JP, Simoneau G, Herbert JM, Savi P, Levy-Toledano S: Effect of clopidogrel administration to healthy volunteers on platelet phosphorylation events triggered by ADP. Br J Haematol. 2003 Feb;120(4):633-42. [12588350 ]
  3. Lev EI, Patel RT, Maresh KJ, Guthikonda S, Granada J, DeLao T, Bray PF, Kleiman NS: Aspirin and clopidogrel drug response in patients undergoing percutaneous coronary intervention: the role of dual drug resistance. J Am Coll Cardiol. 2006 Jan 3;47(1):27-33. Epub 2005 Dec 9. [16386660 ]
  4. Savion N, Varon D: Impact--the cone and plate(let) analyzer: testing platelet function and anti-platelet drug response. Pathophysiol Haemost Thromb. 2006;35(1-2):83-8. [16855351 ]
  5. van Hecken A, Depre M, Wynants K, Vanbilloen H, Verbruggen A, Arnout J, Vanhove P, Cariou R, De Schepper PJ: Effect of clopidogrel on naproxen-induced gastrointestinal blood loss in healthy volunteers. Drug Metabol Drug Interact. 1998;14(3):193-205. [10366994 ]
  6. Craft RM, Chavez JJ, Snider CC, Muenchen RA, Carroll RC: Comparison of modified Thrombelastograph and Plateletworks whole blood assays to optical platelet aggregation for monitoring reversal of clopidogrel inhibition in elective surgery patients. J Lab Clin Med. 2005 Jun;145(6):309-15. [15976759 ]
  7. Chen YG, Xu F, Zhang Y, Ji QS, Sun Y, Lu RJ, Li RJ: Effect of aspirin plus clopidogrel on inflammatory markers in patients with non-ST-segment elevation acute coronary syndrome. Chin Med J (Engl). 2006 Jan 5;119(1):32-6. [16454979 ]
  8. Hulot JS, Bura A, Villard E, Azizi M, Remones V, Goyenvalle C, Aiach M, Lechat P, Gaussem P: Cytochrome P450 2C19 loss-of-function polymorphism is a major determinant of clopidogrel responsiveness in healthy subjects. Blood. 2006 Oct 1;108(7):2244-7. Epub 2006 Jun 13. [16772608 ]
  9. Gansera B, Schmidtler F, Spiliopoulos K, Angelis I, Neumaier-Prauser P, Kemkes BM: Urgent or emergent coronary revascularization using bilateral internal thoracic artery after previous clopidogrel antiplatelet therapy. Thorac Cardiovasc Surg. 2003 Aug;51(4):185-9. [14502454 ]
  10. Bauriedel G, Skowasch D, Schneider M, Andrie R, Jabs A, Luderitz B: Antiplatelet effects of angiotensin-converting enzyme inhibitors compared with aspirin and clopidogrel: a pilot study with whole-blood aggregometry. Am Heart J. 2003 Feb;145(2):343-8. [12595854 ]
  11. Geiger J, Brich J, Honig-Liedl P, Eigenthaler M, Schanzenbacher P, Herbert JM, Walter U: Specific impairment of human platelet P2Y(AC) ADP receptor-mediated signaling by the antiplatelet drug clopidogrel. Arterioscler Thromb Vasc Biol. 1999 Aug;19(8):2007-11. [10446085 ]
  12. Xiao Z, Theroux P: Clopidogrel inhibits platelet-leukocyte interactions and thrombin receptor agonist peptide-induced platelet activation in patients with an acute coronary syndrome. J Am Coll Cardiol. 2004 Jun 2;43(11):1982-8. [15172401 ]
  13. Graff J, Harder S, Wahl O, Scheuermann EH, Gossmann J: Anti-inflammatory effects of clopidogrel intake in renal transplant patients: effects on platelet-leukocyte interactions, platelet CD40 ligand expression, and proinflammatory biomarkers. Clin Pharmacol Ther. 2005 Nov;78(5):468-76. Epub 2005 Sep 26. [16321613 ]
  14. Evangelista V, Manarini S, Dell'Elba G, Martelli N, Napoleone E, Di Santo A, Lorenzet PS: Clopidogrel inhibits platelet-leukocyte adhesion and platelet-dependent leukocyte activation. Thromb Haemost. 2005 Sep;94(3):568-77. [16268474 ]
  15. Ley SJ: Quality care outcomes in cardiac surgery: the role of evidence-based practice. AACN Clin Issues. 2001 Nov;12(4):606-17; quiz 633-5. [11759432 ]
  16. Samara WM, Bliden KP, Tantry US, Gurbel PA: The difference between clopidogrel responsiveness and posttreatment platelet reactivity. Thromb Res. 2005;115(1-2):89-94. [15567458 ]
  17. Cassar K, Bachoo P, Ford I, Greaves M, Brittenden J: Variability in responsiveness to clopidogrel in patients with intermittent claudication. Eur J Vasc Endovasc Surg. 2006 Jul;32(1):71-5. Epub 2006 Mar 23. [16549375 ]
  18. Yende S, Wunderink RG: Effect of clopidogrel on bleeding after coronary artery bypass surgery. Crit Care Med. 2001 Dec;29(12):2271-5. [11801823 ]
  19. Malinin A, Pokov A, Swaim L, Kotob M, Serebruany V: Validation of a VerifyNow-P2Y12 cartridge for monitoring platelet inhibition with clopidogrel. Methods Find Exp Clin Pharmacol. 2006 Jun;28(5):315-22. [16845449 ]
  20. Quinn MJ, Bhatt DL, Zidar F, Vivekananthan D, Chew DP, Ellis SG, Plow E, Topol EJ: Effect of clopidogrel pretreatment on inflammatory marker expression in patients undergoing percutaneous coronary intervention. Am J Cardiol. 2004 Mar 15;93(6):679-84. [15019868 ]

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
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. Acts as a 1,4-cineole 2-exo-monooxygenase.
Gene Name:
CYP2B6
Uniprot ID:
P20813
Molecular weight:
56277.81
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.
Gene Name:
CYP3A5
Uniprot ID:
P20815
Molecular weight:
57108.065
General function:
Involved in binding
Specific function:
Ca(2+)-dependent receptor for myeloid cells that binds to carbohydrates on neutrophils and monocytes. Mediates the interaction of activated endothelial cells or platelets with leukocytes. The ligand recognized is sialyl-Lewis X. Mediates rapid rolling of leukocyte rolling over vascular surfaces during the initial steps in inflammation through interaction with PSGL1
Gene Name:
SELP
Uniprot ID:
P16109
Molecular weight:
90833.1
General function:
Involved in G-protein coupled receptor protein signaling pathway
Specific function:
Receptor for ADP and ATP coupled to G-proteins that inhibit the adenylyl cyclase second messenger system. Not activated by UDP and UTP. Involved in platelets aggregation
Gene Name:
P2RY12
Uniprot ID:
Q9H244
Molecular weight:
39438.4