Key Laboratory of Radiopharmaceuticals, Beijing Normal University, Ministry of Education, Beijing 100875, PR China.
Bioorg Med Chem Lett. 2012 Jul 1;22(13):4303-6. doi: 10.1016/j.bmcl.2012.05.030. Epub 2012 May 15.
A novel series of tropane derivatives containing a fluorinated tertiary amino or amide at the 2β position was synthesized, labeled with the positron-emitter fluorine-18 (t(1/2)=109.8 min), and tested as potential in vivo dopamine transporter (DAT) imaging agents. The corresponding chlorinated analogs were prepared and employed as precursors for radiolabeling leading to the fluorine-18-labeled derivatives via a one-step nucleophilic aliphatic substitution reaction. In vitro binding results showed that the 2β-amino compounds 6b, 6d and 7b displayed moderately high affinities to DAT (K(i)<10nM). Biodistribution studies of [(18)F]6b and [(18)F]6d showed that the brain uptakes in rats were low. This is likely due to their low lipophilicities. Further structural modifications of these tropane derivatives will be needed to improve their in vivo properties as DAT imaging agents.
我们合成了一系列新型托烷衍生物，这些衍生物在 2β 位含有一个氟化的叔氨基或酰胺基，并被放射性核素氟-18（t(1/2)=109.8 min）标记，作为潜在的体内多巴胺转运体（DAT）成像剂进行了测试。还制备了相应的氯化类似物，并将其用作放射性标记的前体，通过一步亲核脂肪取代反应得到氟-18 标记的衍生物。体外结合结果表明，2β-氨基化合物 6b、6d 和 7b 对 DAT 显示出中等亲和力（K(i)<10nM）。[(18)F]6b 和 [(18)F]6d 的体内分布研究表明，这些托烷衍生物在大鼠中的脑摄取量较低。这可能是由于它们的低脂溶性。需要进一步对这些托烷衍生物进行结构修饰，以改善它们作为 DAT 成像剂的体内特性。
