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Synthesis of C‐14 labeled GABA A α2/α3 selective partial agonists and the investigation of late‐occurring and long‐circulating metabolites of GABA A receptor modulator AZD7325
Author(s) -
Artelsmair Markus,
Gu Chungang,
Lewis Richard J.,
Elmore Charles S.
Publication year - 2018
Publication title -
journal of labelled compounds and radiopharmaceuticals
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.432
H-Index - 47
eISSN - 1099-1344
pISSN - 0362-4803
DOI - 10.1002/jlcr.3602
Subject(s) - anxiolytic , pharmacology , chemistry , in vivo , metabolite , gabaa receptor , oxidative metabolism , pharmacokinetics , partial agonist , agonist , tricyclic , receptor , metabolism , biochemistry , stereochemistry , biology , microbiology and biotechnology
Abstract Anxiolytic activity has been associated with GABA A α2 and α3 subunits. Several target compounds were identified and required in C‐14 labeled form to enable a better understanding of their drug metabolism and pharmacokinetic properties. AZD7325 is a selective GABA A α2 and α3 receptor modulator intended for the treatment of anxiety through oral administration. A great number of AZD7325 metabolites were observed across species in vivo , whose identification was aided by [ 14 C] AZD7325 . An interesting metabolic cyclization and aromatization pathway leading to the tricyclic core of M9 and the oxidative pathways to M10 and M42 are presented.