109904-27-0

Basic information

• Product Name: 2-Oxo Clopidogrel Hydrochloride (Mixture of diastereomers)
• Synonyms: a-(2-Chlorophenyl)-2,6,7,7a-tetrahydro-2-oxo-thieno[3,2-c]pyridine-5(4H)-acetic Acid Methyl Ester Hydrochloride;2-OXO CLOPIDOGREL HYDROCHLORIDE;2-Oxo-Clopidogrel-d4 (Mixture of DiastereoMers);2-Oxo Clopidogrel (Mixture of IsoMers);methyl 2-(2-chlorophenyl)-2-(2-oxo-7,7a-dihydrothieno[3,2-c]pyridin-5(2H,4H,6H)-yl)acetate;Methyl (2-Chlorophenyl)(2-Oxo-2,6,7,7alpha-Tetrahydrothieno[3,2-c]Pyridin-5(4H)-Yl)Acetate;2-Oxo Clopidogrel Hydrochloride (Mixture of diastereomers);a-(2-Chlorophenyl)-2,6,7,7a-tetrahydro-2-oxo-thieno[3,2-c]pyridine-5(4H)-acetic Acid Methyl Ester Hydrochlorid
• CAS NO: 109904-27-0
• Molecular Formula: C16H17Cl2NO3S
• Molecular Weight: 374.28208
• Product Categories: Intermediates & Fine Chemicals;Metabolites & Impurities;Pharmaceuticals;Heterocycles;Various Metabolites and Impurities
• Mol File: 109904-27-0.mol

Chemical Properties

• Melting Point: 133-1350C
• Boiling Point: 488.1±45.0 °C(Predicted)
• Appearance: /
• Density: 1.39±0.1 g/cm3(Predicted)
• Storage Temp.: -20°C Freezer
• Solubility: DMSO (Slightly), Methanol (Slightly)
• PKA: 3.41±0.20(Predicted)
• CAS DataBase Reference: 2-Oxo Clopidogrel Hydrochloride (Mixture of diastereomers)(CAS DataBase Reference)
• NIST Chemistry Reference: 2-Oxo Clopidogrel Hydrochloride (Mixture of diastereomers)(109904-27-0)
• EPA Substance Registry System: 2-Oxo Clopidogrel Hydrochloride (Mixture of diastereomers)(109904-27-0)

Safety Data

• Hazardous Substances Data: 109904-27-0(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
2-Oxo Clopidogrel Hydrochloride (Mixture of diastereomers) is used as an intermediate metabolite for the synthesis of the active metabolite of Clopidogrel, which is an antiplatelet drug. This application is crucial in the treatment and prevention of various cardiovascular conditions, such as myocardial infarction, stroke, and peripheral arterial disease, by inhibiting platelet aggregation and reducing the risk of blood clot formation.

Upstream product

• 113665-84-2 (S)-(+)-clopidogrel 
• 10421-85-9 (R)-2-chloromandelic acid 
• 115473-15-9 5,6,7,7a-tetrahydro-thieno[3,2-c]pyridin-2(4H)-one hydrochloride 
• 85259-19-4 methyl 2-bromo-2-(2-chlorophenyl)acetate 
• 32345-59-8 methyl (R)-2-chloromandelate 
• 109904-37-2 5,6,7,7a-tetrahydrothieno[3,2-c]pyridine-2(4H)-one monohydrochloride 
• 32345-60-1 methyl (S)-2-hydroxy-2-(2-chlorophenyl)acetate 
• 156276-21-0 rac-methyl 2-chloromandelate 
• 90055-47-3 methyl 2-chloro-2-(2-chlorophenyl)acetate 

Downstream Products

• 204204-99-9 Clopidogrel active metabolite 
• 1118605-95-0 C₂₆H₃₃ClN₄O₁₀S₂ 
• 1416696-48-4 methyl (7aR,2'S)-2-(2-chlorophenyl)-2-(2,4,5,6,7,7a-hexahydrothieno[3,2-c]-5-pyridin-2-one)acetate 
• 1416696-44-0 methyl (7aS,2'S)-2-(2-chlorophenyl)-2-(2,4,5,6,7,7a-hexahydrothieno[3,2-c]-5-pyridin-2-one)acetate 

Relevant articles and documents

In Vitro Assessment of Potential for CYP-Inhibition-Based Drug–Drug Interaction Between Vonoprazan and Clopidogrel

Background and Objectives: It was recently proposed that CYP-mediated drug–drug interactions (DDIs) of vonoprazan with clopidogrel and prasugrel can attenuate the antiplatelet actions of the latter two drugs. Clopidogrel is metabolized to the pharmacologically active metabolite H4 and its isomers by multiple CYPs, including CYP2C19 and CYP3A4. Therefore, to investigate the possibility of CYP-based DDIs, in vitro metabolic inhibition studies using CYP probe substrates or radiolabeled clopidogrel and human liver microsomes (HLMs) were conducted in this work. Methods: Reversible inhibition studies focusing on the effects of vonoprazan on CYP marker activities and the formation of the [14C]clopidogrel metabolite H4 were conducted with and without pre-incubation using HLMs. Time-dependent inhibition (TDI) kinetics were also measured. Results: It was found that vonoprazan is not a significant direct inhibitor of any CYP isoforms (IC50 ≥ 16?μM), but shows the potential for TDI of CYP2B6, CYP2C19, and CYP3A4/5. This TDI was weaker than the inhibition induced by the corresponding reference inhibitors ticlopidine, esomeprazole, and verapamil, based on the measured potencies (kinact/KI ratio and the R2 value). In a more direct in vitro experiment, vonoprazan levels of up to 10?μM (a 100-fold higher concentration than the plasma Cmax of 75.9?nM after taking 20?mg once daily for 7?days) did not suppress the formation of the active metabolite H4 or other oxidative metabolites of [14C]clopidogrel in a reversible or time-dependent manner. Additionally, an assessment of clinical trials and post-marketing data suggested no evidence of a DDI between vonoprazan and clopidogrel. Conclusions: The body of evidence shows that the pharmacodynamic DDI reported between vonoprazan and clopidogrel is unlikely to be caused by the inhibition of CYP2B6, CYP2C19, or CYP3A4/5 by vonoprazan.

Synthesis of a novel series of amino acid prodrugs based on thienopyridine scaffolds and evaluation of their antiplatelet activity

The thienopyridines class of drugs used as P2Y12 receptor antagonists plays a vital role in antiplatelet therapy. To further optimized this compound class, we designed and synthesized a series of amino acid prodrugs of 2-hydroxytetrahydrothienopyridine. All compounds were then evaluated for their inhibitory effect on ADP-induced platelet aggregation in rats and then ED50 and bleeding time of the most potent compounds were compared with commercial drugs. The results showed compound 5c could be a potent and safe candidate for further research.

STABLE COMPOSITIONS OF (7AS,2'S)-2-OXOCLOPIDOGREL AND ITS PHARMACEUTICAL SALTS

The present invention discloses stable oral pharmaceutical composition containing therapeutically effective amount of (7aS,2'S)-2-oxoclopidogrel and/or its salts or derivatives, in combination with pharmaceutically acceptable adjuvants or carriers. More particularly, the present invention discloses highly pure (7aS,2'S)-2-oxoclopidogrel and/or its salts, processes for manufacturing pure and stable (7aS,2'S)-2-oxoclopidogrel and stable compositions having a shelf-life of at least one year or more.

THIENOPYRIDINE DERIVATIVES CONTAINING UNSATURATED ALIPHATIC OLEFINIC BOND, PREPARATION METHOD AND USE THEREOF

The present invention provides a compound having a structure of formula (I), a preparation method and use thereof, and a pharmaceutical composition containing the compound, wherein R is methyl, ethyl, propyl, vinyl or propenyl. The present invention also

Thiopheneglyoxylic pyridine derivative and its preparation method and medical use

The invention belongs to the field of pharmaceutical chemistry technology, and particularly discloses thienopyridine derivatives, and preparation methods and a medical use thereof. Through structural modification of clopidogrel and prasugrel, a series of new thienopyridine derivative compounds are synthesized and mainly include derivatives esterified with ligustrazine formic acid and shikimic acid; the compounds go into a body, then are rapidly metabolized into effective metabolites and ligustrazine formic acid or shikimic acid, successfully keep away from metabolism of CYP2C19 enzyme, can be directly metabolized into active compounds to play a pharmacological function, thereby solving the clopidogrel resistance problem, effectively improving the compound antithrombotic activity, and also having no significant effect on hemorrhage risk; and the compounds have relatively ideal protective function on liver and kidney, and also have potential therapeutic significance for other cardiovascular diseases.

Synthesis of Biologically Active Piperidine Metabolites of Clopidogrel: Determination of Structure and Analyte Development

Clopidogrel is a prodrug anticoagulant with active metabolites that irreversibly inhibit the platelet surface GPCR P2Y12 and thus inhibit platelet activation. However, gaining an understanding of patient response has been limited due to imprecise understanding of metabolite activity and stereochemistry, and a lack of acceptable analytes for quantifying in vivo metabolite formation. Methods for the production of all bioactive metabolites of clopidogrel, their stereochemical assignment, and the development of stable analytes via three conceptually orthogonal routes are disclosed. (Chemical Equation Presented).

Bioactivation of Clopidogrel and Prasugrel: Factors Determining the Stereochemistry of the Thiol Metabolite Double Bond

The antithrombotics of the tetrahydrothienopyridine series, clopidogrel and prasugrel, are prodrugs that must be metabolized in two steps to become pharmacologically active. The first step is the formation of a thiolactone metabolite. The second step is a further oxidation with the formation of a thiolactone sulfoxide whose hydrolytic opening leads to a sulfenic acid that is eventually reduced into the corresponding active cis thiol. Very few data were available on the formation of the isomer of the active cis thiol having a trans configuration of the double bond, the most striking result in that regard being that both cis and trans thiols were formed upon the metabolism of clopidogrel by human liver microsomes in the presence of glutathione (GSH), whereas only the cis thiol was detected in the sera of patients treated with this drug. This article shows that trans thiols are also formed upon the microsomal metabolism of prasugrel or its thiolactone metabolite in the presence of GSH and that metabolites having the trans configuration of the double bond are only formed when microsomal incubations are done in the presence of thiols, such as GSH, N-acetyl-cysteine, and mercaptoethanol. Intermediate formation of thioesters resulting from the reaction of GSH with the thiolactone sulfoxide metabolite appears to be responsible for trans thiol formation. Addition of human liver cytosol to the microsomal incubations led to a dramatic decrease of the formation of the trans thiol metabolites. These data suggest that cytosolic esterases would accelerate the hydrolytic opening of thiolactone sulfoxide intermediates and disfavor the formation of thioesters resulting from the reaction of these intermediates with GSH that is responsible for trans isomer formation. This would explain why trans thiols have not been detected in the sera of patients treated with clopidogrel.

ANTI-THROMBOTIC COMPOUNDS

New compounds, namely, (7aS,2'S)-2-oxoclopidogrel and its pharmaceutically acceptable salts thereof are disclosed for treatment or prophylaxis of thrombo-embolism and/or cardiovascular diseases.

OPTICALLY ACTIVE 2-HYDROXY TETRAHYDROTHIENOPYRIDINE DERIVATIVES, PREPARATION METHOD AND USE IN MANUFACTURE OF MEDICAMENT THEREOF

Optically active 2-hydroxytetrahydrothienopyridine derivatives represented by Formula I and pharmaceutically acceptable salts, preparation method and use in the manufacture of a medicament thereof are disclosed. The pharmacodynamic experiment results show that the present compounds of Formula I are useful for inhibiting platelet aggregation. The pharmacokinetic experiment results show that the present compound of Formula I can be converted in vivo into pharmacologically active metabolites and are therefore useful for inhibiting platelet aggregation. Therefore, the present compounds are useful for the manufacture of a medicament for preventing or treating thrombosis and embolism related diseases.

ANTI-THROMBOTIC COMPOUNDS

New compounds, namely, (7aS,2′S)-2-oxoclopidogrel and its pharmaceutically acceptable salts thereof are disclosed for treatment or prophylaxis of thrombo-embolism and/or cardiovascular diseases.