Moldovan Rareş-Petru, Hausmann Kristin, Deuther-Conrad Winnie, Brust Peter
Helmholtz-Zentrum Dresden-Rossendorf e.V., Institute of Radiopharmaceutical Cancer Research, Permoserstraße 15, Leipzig 04318, Germany.
ACS Med Chem Lett. 2017 Apr 28;8(5):566-571. doi: 10.1021/acsmedchemlett.7b00129. eCollection 2017 May 11.
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.
2型大麻素受体（CB受体）参与多种病理过程，利用正电子发射断层扫描（PET）对其可用性进行可视化研究备受关注。该研究重点在于将氟引入高亲和力和选择性的CB受体配体 -（金刚烷-1-基）-5-乙基-2-甲基-1-苯基-1-咪唑-4-甲酰胺（）的结构中。通过修饰（i）金刚烷的3-位、（ii）咪唑-苯环和（iii）咪唑的2-位，开发了一系列新化合物，并评估了其对CB结合亲和力以及对1型大麻素受体（CB）选择性的影响。该研究确定化合物是迄今为止发现的最有效（（CB）= 0.29 nM）且选择性最高（CB/CB > 10000）的CB受体配体之一，有资格用于开发F标记的PET放射性示踪剂。
