A new series of derivatives of 3-(1,4-diazabicyclo[3.2.2]nonan-4-yl)dibenzo[b,d]thiophene 5,5-dioxide with high binding affinities and selectivity for α7-nicotinic acetylcholine receptors (α7-nAChRs) (K_i = 0.4–20 nM) has been synthesized for positron emission tomography (PET) imaging of α7-nAChRs. Two radiolabeled members of the series [¹⁸F]7a (K_i = 0.4 nM) and [¹⁸F]7c (K_i = 1.3 nM) were synthesized. [¹⁸F]7a and [¹⁸F]7c readily entered the mouse brain and specifically labeled α7-nAChRs. The α7-nAChR selective ligand 1 (SSR180711) blocked the binding of [¹⁸F]7a in the mouse brain in a dose-dependent manner. The mouse blocking studies with non-α7-nAChR central nervous system drugs demonstrated that [¹⁸F]7a is highly α7-nAChR selective. In agreement with its binding affinity the binding potential of [¹⁸F]7a (BP_ND = 5.3–8.0) in control mice is superior to previous α7-nAChR PET radioligands. Thus, [¹⁸F]7a displays excellent imaging properties in mice and has been chosen for further evaluation as a potential PET radioligand for imaging of α7-nAChR in non-human primates.

中文翻译：

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二苯并噻吩衍生物用于 α7-烟碱乙酰胆碱受体的正电子发射断层扫描成像

3-(1,4-二氮杂双环[3.2.2]壬烷-4-基)二苯并[ b , d ]噻吩5,5-二氧化物的一系列新衍生物，对α7-烟碱乙酰胆碱受体具有高结合亲和力和选择性（ α7-nAChRs) ( K _i = 0.4–20 nM) 已被合成用于 α7-nAChRs 的正电子发射断层扫描 (PET) 成像。合成了[ ¹⁸ F] 7a ( K _i = 0.4 nM) 和[ ¹⁸ F] 7c ( K _i = 1.3 nM)系列的两个放射性标记成员。[ ¹⁸ F] 7a和 [ ¹⁸ F] 7c很容易进入小鼠大脑并专门标记了 α7-nAChR。α7-nAChR 选择性配体1 (SSR180711)以剂量依赖性方式阻断小鼠脑中[ ¹⁸ F] 7a的结合。使用非 α7-nAChR 中枢神经系统药物进行的小鼠阻断研究表明 [ ¹⁸ F] 7a具有高度的 α7-nAChR 选择性。与其结合亲和力一致，[ ¹⁸ F] 7a (BP _ND = 5.3–8.0) 在对照小鼠中的结合潜力优于之前的 α7-nAChR PET 放射性配体。因此，[ ¹⁸ F] 7a 在小鼠中显示出优异的成像特性，并已被选作进一步评估作为潜在的 PET 放射性配体，用于在非人类灵长类动物中对 α7-nAChR 进行成像。