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.