204204-99-9

Upstream product

• 109904-27-0 (SR)-methyl 2-(2-chlorophenyl)-2-(2-oxo-7,7a-dihydrothieno-[3,2-c]pyridin-5(2H,4H,6H)-yl)acetate 
• 1118605-95-0 C₂₆H₃₃ClN₄O₁₀S₂ 
• 1147350-75-1 2-Oxoclopidogrel 

Relevant academic research and scientific papers

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.

MIXED DISULFIDE CONJUGATES OF THIENOPYRIDINE COMPOUNDS AND USES THEREOF

This invention is in the field of medicinal chemistry. In particular, the invention relates to mixed disulfide conjugates of thienopyridine compounds, and their use as therapeutics for the treatment, amelioration, and prevention of cardiovascular diseases

Formation, reactivity, and antiplatelet activity of mixed disulfide conjugates of clopidogrel

In this work, we investigated the formation, reactivity, and antiplatelet activity of various mixed disulfide conjugates of clopidogrel. Our results showed that the production of the active metabolite (AM) from 2-oxoclopidogrel by human liver microsomes (HLMs) is greatly affected by the thiol reductants used. Among the 10 thiol compounds tested, glutathione (GSH) is most efficient in producing the AM at a rate of 167 pmoles AM/ min/mg HLM. Interestingly, no AM but only the mixed disulfide conjugates were formed in the presence of 6-chloropyridazine- 3-thiol (CPT), 2,5-dimethylfuran-3-thiol, and 3-nitropyridine-2- thiol (NPT). The mass spectrometry (MS) and MS2 spectra of the conjugates of these thiol compounds confirmed the presence of a mixed disulfide bond linkage between the AM and the thiol reductants. Kinetic studies revealed that the mixed disulfide conjugates were capable of exchanging thiols with GSH to release the AM with second order rate constants ranging from 1.2 to 28 M21s21. The mixed disulfide conjugates of CPT and NPT showed potent inhibition of platelet aggregation after pretreatment with 1 mM GSH, confirming that the AM is responsible for the antiplatelet activity of clopidogrel. Collectively, our results provide strong support for a cytochrome P450 (P450)-mediated bioactivation mechanism involving the initial formation of a glutathionyl conjugate, followed by thiol-disulfide exchange with another GSH molecule to release the AM. Furthermore, the stable mixed disulfide conjugates identified in this study provide a platform to quantitatively generate the therapeutic AM without the need for P450- mediated bioactivation. This property can be further explored to overcome the interindividual variability in clopidogrel therapy. Copyright