Key Laboratory of Radiopharmaceuticals (Beijing Normal University), Ministry of Education, Beijing 100875, PR China.
Bioorg Med Chem Lett. 2011 May 15;21(10):2962-5. doi: 10.1016/j.bmcl.2011.03.051. Epub 2011 Mar 21.
A series of novel N-fluoropyridyl-containing tropane derivatives were synthesized and their binding affinities for the dopamine transporter (DAT), serotonin transporter (SERT) and norepinephrine (NET) were determined via competitive radioligand binding assays. Among these derivatives, compound 6d showed the highest binding affinity to DAT (K(i)=4.1 nM), and selectivity for DAT over SERT (5-fold) and NET (16-fold). Compound 6d was radiolabeled with Fluorine-18 in two steps. Regional brain distribution and ex vivo autoradiography studies of [(18)F]6d demonstrated that the ligand was selectively localized in the striatum region, where DAT binding sites are highly expressed. [(18)F]6d may be useful as a potential radioligand for imaging DATs with PET.
一系列新型含 N-氟吡啶的托烷衍生物被合成出来，并通过竞争性放射性配体结合实验测定了它们对多巴胺转运体（DAT）、5-羟色胺转运体（SERT）和去甲肾上腺素（NET）的结合亲和力。在这些衍生物中，化合物 6d 对 DAT 的亲和力最高（Ki=4.1 nM），对 DAT 的选择性是 SERT 的 5 倍，NET 的 16 倍。化合物 6d 经两步法用氟-18 进行放射性标记。[(18)F]6d 的脑区分布和离体放射性自显影研究表明，该配体选择性地定位于纹状体区域，该区域 DAT 结合位点高表达。[(18)F]6d 可能是一种用于 PET 成像 DAT 的潜在放射性配体。
