Synthesis of C-14 labeled GABAA α2/α3 selective partial agonists and the investigation of late-occurring and long-circulating metabolites of GABAA receptor modulator AZD7325.

Abstract

Anxiolytic activity has been associated with GABAA 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 GABAA 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 [14C]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.