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

Abstract

Cannabinoid type 2 receptors (CB2 receptors) are involved in various pathological processes, and the visualization of their in vivo 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 CB2 receptor ligand N-(adamantan-1-yl)-5-ethyl-2-methyl-1-phenyl-1H-imidazole-4-carboxamide (5). A novel series of compounds was developed by modifying (i) the adamantane-3-position, (ii) the imidazole-N-phenyl ring, and (iii) the imidazole-2-position, and the impact on the CB2 binding affinity and selectivity toward cannabinoid type 1 receptors (CB1) was evaluated. This study identified compound 15 as one of the most potent (Ki(CB2) = 0.29 nM) and selective (CB1/CB2 > 10000) CB2 receptor ligands discovered so far, eligible for the development of an 18F-labeled PET radiotracer.

• Authors: Rareş-Petru Moldovan, Kristin Hausmann, Winnie Deuther-Conrad, Peter Brust
• Journal: ACS medicinal chemistry letters (ACS Med Chem Lett) Vol. 8 Issue 5 Pg. 566-571 (May 11 2017) ISSN: 1948-5875 [Print] United States
• PMID: 28523112 (Publication Type: Journal Article)