Synthesis of Biologically Active Piperidine Metabolites of Clopidogrel: Determination of Structure and Analyte Development
Synthesis of Biologically Active Piperidine Metabolites of Clopidogrel: Determination of Structure and Analyte Development
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DOI：
10.1021/acs.joc.5b00632
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发表时间：
2015-07-17
影响因子：
3.6
通讯作者：
Baran, Phil S.
中科院分区：
文献类型：
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作者：
Shaw, Scott A.;Balasubramanian, Balu;Baran, Phil S.
氯吡格雷是一种前体药物抗凝剂，其活性代谢产物可不可逆地抑制血小板表面GPCR P2Y（12），从而抑制血小板活化。然而，由于对代谢物活性和立体化学的不精确理解，以及缺乏可接受的用于定量体内代谢物形成的分析物，因此对患者反应的理解受到限制。公开了通过三种概念上正交的途径生产氯吡格雷的所有生物活性代谢物、它们的立体化学分配和开发稳定分析物的方法。
Clopidogrel is a pro drug anticoagulant with active metabolites that irreversibly inhibit the platelet surface GPCR P2Y(12) 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.