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

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• 作者：Scott A. Shaw ; Balu Balasubramanian ; Samuel Bonacorsi ; Janet Caceres Cortes ; Kevin Cao ; Bang-Chi Chen ; Jun Dai ; Carl Decicco ; Animesh Goswami ; Zhiwei Guo ; Ronald Hanson ; W. Griffith Humphreys ; Patrick Y. S. Lam ; Wenying Li ; Arvind Mathur ; Brad D. Maxwell ; Quentin Michaudel ; Li Peng ; Andrew Pudzianowski ; Feng Qiu ; Shun Su ; Dawn Sun ; Adrienne A. Tymiak ; Benjamin P. Vokits ; Bei Wang ; Ruth Wexler ; Dauh-Rurng Wu ; Yingru Zhang ; Rulin Zhao ; Phil S. Baran
• 刊名：Journal of Organic Chemistry
• 出版年：2015
• 出版时间：July 17, 2015
• 年：2015
• 卷：80
• 期：14
• 页码：7019-7032
• 全文大小：735K
• ISSN：1520-6904

文摘

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.