Synthesis of Biologically Active Piperidine Metabolites of Clopidogrel: Determination of Structure and Analyte Development.
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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.
author list (cited authors)
Shaw, S. A., Balasubramanian, B., Bonacorsi, S., Cortes, J. C., Cao, K., Chen, B., ... Baran, P. S
complete list of authors
Shaw, Scott A||Balasubramanian, Balu||Bonacorsi, Samuel||Cortes, Janet Caceres||Cao, Kevin||Chen, Bang-Chi||Dai, Jun||Decicco, Carl||Goswami, Animesh||Guo, Zhiwei||Hanson, Ronald||Humphreys, W Griffith||Lam, Patrick YS||Li, Wenying||Mathur, Arvind||Maxwell, Brad D||Michaudel, Quentin||Peng, Li||Pudzianowski, Andrew||Qiu, Feng||Su, Shun||Sun, Dawn||Tymiak, Adrienne A||Vokits, Benjamin P||Wang, Bei||Wexler, Ruth||Wu, Dauh-Rurng||Zhang, Yingru||Zhao, Rulin||Baran, Phil S