Synthesis and evaluation of novel tropane derivatives as potential PET imaging agents for the dopamine transporter

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

卷:22

Article

Qiao, Hongwen^1,2  Zhu, Lin^1,2  Lieberman, Brian P.²  Zha, Zhihao²  Ploessl, Karl²  Kung, Hank F.^1,2,3 

[1] Beijing Normal Univ, Minist Educ, Key Lab Radiopharmaceut, Beijing 100875, Peoples R China

[2] Univ Penn, Dept Radiol, Philadelphia, PA 19104 USA

[3] Univ Penn, Dept Pharmacol, Philadelphia, PA 19104 USA

关键词: Dopamine transporter;    Tropane;    Fluorine-18;    Imaging tracers;    PET;   

DOI  :  10.1016/j.bmcl.2012.05.030

来源: Elsevier

【 摘 要 】

A novel series of tropane derivatives containing a fluorinated tertiary amino or amide at the 2 beta 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 2 beta-amino compounds 6b, 6d and 7b displayed moderately high affinities to DAT (K-i < 10 nM). Biodistribution studies of [F-18]6b and [F-18]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. (C) 2012 Published by Elsevier Ltd.

【 授权许可】

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