Central nervous system disorders related to neuroinflammation and neurodegeneration like the Alzheimer’s disease (AD) are often multifactorial and thus difficult to treat. One promising target is the human cannabinoid receptor subtype 2 (hCB2R), which is rapidly upregulated in neuroinflammatory processes, like in microglia that surround amyloid beta plaques in AD. For this reason, selective activation of hCB2R is of interest in AD research. In order to understand the activation mechanism, to gain partial agonism and to avoid undesirable side effects, like off-target binding, we applied the dualsteric targeting strategy. Therefore, ligands are produced which simultaneously bind the orthosteric and an allosteric binding site of a receptor. Herein we present the synthesis of two sets of potential dualsteric ligands, which were evaluated in several in vitro assays and show novel and interesting pharmacological profiles.

Dualsteric targeting of the cannabinoid CB2 receptor

ACS Spring 2022

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.