Development of Highly Affine and Selective Fluorinated Cannabinoid Type 2 Receptor Ligands.

Cannabinoid type 2 receptors (CB receptors) are involved in various pathological processes, and the visualization of their availability with positron emission tomography (PET) is of high interest. The study focuses on the introduction of fluorine into the structure of the highly affine and selective CB receptor ligand -(adamantan-1-yl)-5-ethyl-2-methyl-1-phenyl-1-imidazole-4-carboxamide (). A novel series of compounds was developed by modifying (i) the adamantane-3-position, (ii) the imidazole--phenyl ring, and (iii) the imidazole-2-position, and the impact on the CB binding affinity and selectivity toward cannabinoid type 1 receptors (CB) was evaluated. This study identified compound as one of the most potent ((CB) = 0.29 nM) and selective (CB/CB > 10000) CB receptor ligands discovered so far, eligible for the development of an F-labeled PET radiotracer.