Polycyclic Maleimide-based Scaffold as New Privileged Structure for Navigating the Cannabinoid System Opportunities

The discovery of the relevant role played by a dysregulation of the endogenous cannabinoid system in several pathological conditions has prompted an extensive research in this field. In this Letter, a series of cannabinoid receptor ligands bearing a previously unexplored polycyclic scaffold was designed and synthesized, in order to evaluate the potential of a new easily affordable privileged structure. The new compounds showed an appreciable affinity and a significant selectivity for the CB2 receptor and are endowed with an intriguing noncompetitive antagonist behavior. Due to the ability of the polycyclic structure to be easily modified in different ways, these compounds could represent convenient chemical tools to be exploited in order to better understand the endocannabinoid system impact on physiopathological conditions.