113665-84-2 Usage
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
Different sources of media describe the Uses of 113665-84-2 differently. You can refer to the following data:
1. anthelmintic, antiparasitic, antimite
2. Sertraline metabolite
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 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 clopidogrel hydrogen sulfate crystal form II
-
Paragraph 0044; 0054; 0058; 0070; 0073, (2020/02/29)
The invention discloses a preparation method of a clopidogrel hydrogen sulfate crystal form II. The method includes: preparation of (+)o-chlorophenylglycine methyl ester; preparation of (+)alpha-(2-thiophene ethylamino)-alpha-(2-chlorphenyl)methyl acetate hydrochloride; preparation of (+)clopidogrel free alkali; preparation of (+)clopidogrel camphorsulfonic acid double salt; hydrolysis of (+)clopidogrel camphorsulfonic acid double salt; and preparation of clopidogrel hydrogen sulfate. The preparation method of the clopidogrel hydrogen sulfate crystal form II provided by the invention optimizesthe synthesis process of clopidogrel hydrogen sulfate, selects cheap and easily available materials, adopts mild reaction conditions, and can achieve safe and environment-friendly production of a high-purity product.
