Exploring 1-adamantanamine as an alternative amine moiety for metabolically labile azepane ring in newly synthesized benzo[]thiazol-2(3)one σ receptor ligands.

In this work we report the structure-activity relationships, binding properties, and metabolic stability studies of a series of benzo[]thiazol-2(3)one as sigma receptors (σRs) ligands. Specifically, to improve the metabolic stability of the cyclic amine fragment of our lead compound (), the metabolically unstable azepane ring was replaced with a 1-adatamantamine moiety. Within the synthesized analogs, compound had low nanomolar affinity for the σR ( = 7.2 nM) and moderate preference (61-fold) over the σR. metabolic stability studies showed a slight improvement of the metabolic stability for -, even though an extensive metabolism in rat liver microsomes is being observed. Furthermore, metabolic soft spot identification of suggested that the -methyl group of the adamantyl moiety is a major site of metabolism.