To analyze the N‐methyl‐d‐aspartate (NMDA) receptor distribution in the central nervous system, fluorinated ligands that selectively address the ifenprodil binding site of GluN2B‐subunit‐containing NMDA receptors were developed. Various strategies to introduce a fluorine atom into the potent GluN2B ligand 2 (3‐(4‐phenylbutyl)‐2,3,4,5‐tetrahydro‐1H‐3‐benzazepin‐1,7‐diol) were pursued, including replacement of the benzylic OH moiety with a fluorine atom (13) and introduction of fluoroethoxy moieties at various positions (14 (7‐position), 17 (9‐position), 18a–c (1‐position)). With respect to GluN2B affinity and selectivity over related receptors, the fluoroethoxy derivatives 14 and 18a are the most promising ligands. Radiosynthesis of fluoroethoxy derivative [¹⁸F]14 was performed by nucleophilic substitution of the phenol 2 with 2‐[¹⁸F]fluoroethyl tosylate. On rat brain slices the fluorinated PET tracer [¹⁸F]14 accumulated in regions with high density of NMDA receptors containing GluN2B subunits. The bound radioactivity could not be replaced by (S)‐glutamate. However, the GluN2B ligands eliprodil, Ro 25‐6981, and the non‐labeled 3‐benzazepine 14 were able to abolish the specific binding of [¹⁸F]14.

中文翻译：

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氟化GluN2B受体拮抗剂与3-Benzazepine支架设计用于PET研究

为了分析Ñ甲基d天冬氨酸（NMDA）受体在中枢神经系统中的分布，氟化的配体选择性地解决艾芬地尔结合含GluN2B亚基-NMDA受体的位点被开发出来。采取了各种方法将氟原子引入有效的GluN2B配体2（3-（4-苯基丁基）-2,3,4,5-四氢-1 H -3-苯并ze庚因-1,7-二醇），包括取代含氟原子的苄基OH部分（13）以及在不同位置引入氟乙氧基部分（14（7位），17（9位），18a – c（1位））。关于GluN2B对相关受体的亲和力和选择性，氟乙氧基衍生物14和18a是最有前途的配体。氟乙氧基衍生物[ ¹⁸ F] 14的放射性合成是通过苯酚2被2- [ ¹⁸ F]氟乙基甲苯磺酸酯的亲核取代而进行的。在大鼠脑片上，氟化PET示踪剂[ ¹⁸ F] 14积累在含有GluN2B亚基的NMDA受体高密度区域中。结合的放射性不能被（S）-谷氨酸替代。但是，GluN2B配体依洛替尼，Ro 25‐6981和未标记的3-benzazepine 14能够取消[ ¹⁸ F] 14的特异性结合。