113665-84-2 Usage
Description
Clopidogrel, also known as methyl (+)-(S)-α-(2-chlorophenyl)-6,7-dihydrothieno[3,2-c]pyridine-5(4H)-acetate sulfate (Plavix), is a potent inhibitor of platelet aggregation used for the preventive management of secondary ischemic events, such as myocardial infarction, stroke, and vascular deaths. It belongs to the thienopyridine class of compounds and acts as an adenosine diphosphate (ADP) antagonist at the purinergic P2Y receptor, inhibiting platelet aggregation and reducing the risk of thrombotic events.
Uses
Used in Pharmaceutical Industry:
Clopidogrel is used as an antithrombotic agent for the prevention of secondary ischemic events, such as myocardial infarction, stroke, and vascular deaths. It works by inhibiting the purinergic P2Y receptor on platelets, reducing platelet aggregation and adhesion to the vascular subendothelium, and decreasing myointimal thickening after endothelial injury.
Used in Clinical Trials:
Clopidogrel is used as a test subject in clinical trials, such as the CAPRIE trial (Clopidogrel versus Aspirin in patients at risk of ischemic events), to evaluate its effectiveness and safety compared to other antithrombotic agents like aspirin. The results of these trials have demonstrated that clopidogrel is well-tolerated and more effective than aspirin in preventing ischemic events.
Brand Names:
Clopidogrel is marketed under the brand names Plavix (Sanofi Aventis) and Iscover.
Originator
Sanofi (France)
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 derivativeClopidogrel 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.
Check Digit Verification of cas no
The CAS Registry Mumber 113665-84-2 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 1,1,3,6,6 and 5 respectively; the second part has 2 digits, 8 and 4 respectively.
Calculate Digit Verification of CAS Registry Number 113665-84:
(8*1)+(7*1)+(6*3)+(5*6)+(4*6)+(3*5)+(2*8)+(1*4)=122
122 % 10 = 2
So 113665-84-2 is a valid CAS Registry Number.
113665-84-2Relevant articles and documents
Modified asymmetric strecker reaction of aldehyde with secondary amine: A protocol for the synthesis of S-clopidogrel (an antiplatelet agent)
Sadhukhan, Arghya,Saravanan,Khan, Noor-Ul H.,Kureshy, Rukhsana I.,Abdi, Sayed H. R.,Bajaj, Hari C.
, p. 7076 - 7080 (2012)
A first approach for catalytic asymmetric Strecker reaction of aldehydes with a secondary amine in the presence of sodium fluoride using hydroquinine as chiral catalyst was developed. The catalytic system gave α-aminonitriles in excellent yields (up to 95
Synthetic improvements in the preparation of clopidogrel
Wang, Lixin,Shen, Jianfen,Tang, Yi,Chen, Yi,Wang, Wen,Cai, Zegui,Du, Zhenjun
, p. 487 - 489 (2007)
Synthetic improvements in the preparation of clopidogrel are described. The synthesis was accomplished in four steps or one-pot in above 70% overall yield. The process featured PTC catalyzed alkaline hydrolysis of the key intermediate 2-(2-chlorophenyl)-2-(6,7-dihydrothieno[3,2-c]pyridin-5(4H)-yl)acetonitrile and highly effective kinetic resolution of racemic clopidogrel using L-camphorsulphonic acid in toluene and has been successfully used in a 50-kg pilot test.
Copper (II) bromide catalysed one pot bromination and amination for the green, cost-effective synthesis of clopidogrel
Kumar, K. Naveen,Mhate, Mouzma,Panchami, Hirave,Ravichandiran, V.,Swain, Sharada Prasanna
, (2022/03/15)
Copper (II) bromide catalyzed one pot α-bromination and followed by amination of a benzylic ester is reported. The α-bromination of ester by copper (II) bromide generates copper (I) bromide and HBr. The copper (I) bromide is oxidized to copper (II) bromide by N-Methylmorpholine-N-Oxide (NMO) in presence of HBr. The amines undergo nucleophilic substitution reaction with α-brominated ester compound. This methodology was applied for the synthesis of the familiar antiplatelet drug clopidogrel. This green process is an alternate to classical methods for the synthesis of clopidogrel, which requires, generates stochiometric amount of brominating agents and HBr, respectively.
Preparation method of sulfonic clopidogrel impurity
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Paragraph 0012; 0037-0038, (2020/08/02)
The invention discloses a preparation method of a sulfonic clopidogrel impurity. The preparation method comprises the following steps: reacting thiophene-2-ethanol with toluenesulfonyl chloride to generate p-toluenesulfonic acid-2-thienylethyl ester; carrying out esterification on o-chlorophenylglycine and methanol to generate o-chlorophenylglycine methyl ester; resolving the o-chlorophenylglycinemethyl ester by using L(+) tartaric acid; converting into free S-(+)-o-chlorophenylglycine methyl ester in dichloromethane; carrying out a condensation reaction on the p-toluenesulfonic acid-2-thienylethyl ester and the S-(+)-o-chlorophenylglycine methyl ester under an alkaline condition; acidifying the obtained product to generate (S)-2-(2-thienylethylamino)(2-chlorphenyl)methyl acetate, carrying out a condensation reaction on the (S)-2-(2-thienylethylamino)(2-chlorphenyl)methyl acetate and formaldehyde to obtain clopidogrel, and carrying out a reaction on the clopidogrel and chlorosulfonicacid to generate sulfonic clopidogrel impurity. The preparation method of the sulfonic clopidogrel impurity has the advantages of mild reaction conditions, accessible raw materials, low cost and highyield and purity.