Clopidogrel Property

alpha 

D20 +51.52° (c = 1.61 in methanol)

Boiling point:

423.7±45.0 °C(Predicted)

Density 

1.317±0.06 g/cm3(Predicted)

storage temp. 

2-8°C

solubility 

DMSO: 50mg/ml in DMSO

pka

4.56±0.20(Predicted)

InChI

InChI=1/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-/s3

InChIKey

GKTWGGQPFAXNFI-UJHUVDBMNA-N

SMILES

[C@@H](C1C=CC=CC=1Cl)(N1CCC2SC=CC=2C1)C(=O)OC |&1:0,r|

CAS DataBase Reference

113665-84-2(CAS DataBase Reference)

Safety

Hazard Codes 

Xn

Risk Statements 

22-36/37/38

Safety Statements 

26-36

Hazardous Substances Data

113665-84-2(Hazardous Substances Data)

Hazard and Precautionary Statements (GHS)

Symbol(GHS)

Signal word

Warning

Hazard statements

H302Harmful if swallowed

H315Causes skin irritation

H319Causes serious eye irritation

H335May cause respiratory irritation

Precautionary statements

P261Avoid breathing dust/fume/gas/mist/vapours/spray.

P305+P351+P338IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continuerinsing.

Clopidogrel Chemical Properties,Usage,Production

Description

Clopidogrel was launched in the US as a potent inhibitor of platelet aggregation for the preventive management of secondary ischemic events, including MI, stroke and vascular deaths. Clopidogrel can be synthesized in 4 steps (including an optical resolution to the S active enantiomer) from 2-(2- ch1orophenyl)-glycine, the key step being the cyclization to thienopyridine with formaldehyde and acetic acid. Clopidogrel belongs to the original chemical class of Ticlopidine, but shows fewer side effects (in particular, bone-marrowsuppressing effects) at the dosage generally used. Like Ticlopidine, it is an Adenosine diphosphate (ADP) antagonist acting at the purinergic P2y receptor. In in vivo experiments with rabbits, Clopidogrel shows a maximal antiaggregant effect at 20mg/kg po, reducing adhesion of platelets to the vascular subendothelium ; moreover, it reduces myointimal thickening occuring after endothelial injury of rat carotid artery. Clopigrel does not affect platelet aggregation in vitro ; actually, its in vivo activity is highly dependent on hepatic metabolism. The results of a CAPRIE trial (Clopidogrel versus Aspirin in patients at risk of ischemic events) demonstrated that Clopidogrel was well tolerated and more effective than aspirin.

Originator

Sanofi (France)

Uses

anthelmintic, antiparasitic, antimite

Uses

Sertraline metabolite

Definition

ChEBI: Clopidogrel is a thienopyridine that is 4,5,6,7-tetrahydrothieno[3,2-c]pyridine in which the hydrogen attached to the nitrogen is replaced by an o-chlorobenzyl group, the methylene hydrogen of which is replaced by a methoxycarbonyl group (the S enantiomer). A P2Y12 receptor antagonist, it is used to inhibit blood clots and prevent heart attacks. It has a role as a platelet aggregation inhibitor, an anticoagulant and a P2Y12 receptor antagonist. It is a thienopyridine, a member of monochlorobenzenes and a methyl ester. It is functionally related to a ticlopidine.

brand name

Plavix (Sanofi Aventis);Plavix, Iscover.

General Description

Clopidogrel, methyl (+)-(S)-α-(2-chlorophenyl)-6,7-dihydrothieno[3,2-c]pyridine-5(4H)-acetate sulfate (Plavix), is useful for the preventativemanagement of secondary ischemic events, including myocardialinfarction, stroke, and vascular deaths. It may beclassified as a thienopyridine because of its heterocyclicsystem. Several agents possessing this system have beenevaluated as potential antithrombotic agents. These agentshave a unique mechanism, in that they inhibit the purinergicreceptor located on platelets. Normally, nucleotides act asagonists on these receptors, which include the P2Y type.Two P2Y receptor subtypes (P2Y1 and P2Y2) found onplatelets, when stimulated by adenosine diphosphate (ADP),cause platelet aggregation.

Clinical Use

Clopidogrel acts as an antagonistto the P2Y2 receptor. It is probably a prodrug that requiresmetabolic activation, because in vitro studies do not interferewith platelet aggregation. Although platelet aggregationis not normally seen in the first 8 to 11 days after administrationto a patient, the effect lasts for several days after thedrug therapy is discontinued. Unlike other thienopyridinescurrently used, clopidogrel does not seriously reduce thenumber of white cells in the blood, and therefore, routinemonitoring of the white blood cell count is not necessaryduring treatment.

Drug interactions

Potentially hazardous interactions with other drugs
Antibacterials: antiplatelet effect possibly reduced by erythromycin.
Anticoagulants: enhanced anticoagulant effect with coumarins and phenindione; manufacturer advises to avoid with warfarin.
Heparin: increased risk of bleeding.
Antidepressants: antiplatelet effect possibly reduced by fluoxetine, fluvoxamine and moclobemide.
Anti-diabetics: avoid with repaglinide if possible due to increased repaglinide exposure.
Antiepileptics: antiplatelet effect possibly reduced by carbamazepine and oxcarbazepine.
Antifungals: antiplatelet effect possibly reduced by fluconazole, itraconazole, ketoconazole and voriconazole.
Antivirals: antiplatelet effect possibly reduced by etravirine.
Statins: concentration of rosuvastatin increased, maximum rosuvastatin dose is 20 mg.
Ulcer healing drugs: antiplatelet effect possibly reduced by cimetidine, lansoprazole, pantoprazole and rabeprazole; antiplatelet effect reduced by omeprazole and esomeprazole - avoid concomitant use if possible.

Metabolism

Clopidogrel is a prodrug and is extensively metabolised in the liver, mainly to the inactive carboxylic acid derivative; metabolism is mediated by cytochrome P450 isoenzymes including CYP3A4 and CYP2B6, CYP1A2, CYP1A1, and CYP2C19. The active metabolite appears to be a thiol derivative
Clopidogrel and its metabolites are excreted in urine and in faeces; about 50% of an oral dose is recovered from the urine and about 46% from the faeces.