A series of iodinated ligands for the SPECT imaging of 5-HT4 receptors was designed starting from the previously reported hit MR-26132. We focused on the modulation of the piperidine-containing lateral chain by introducing hydrophilic groups in order to decrease the liphophilicity of the new ligands. All the synthesized compounds were tested for their binding affinities on 5-HT4Rs and based on the Ligand Lipophilicity Efficiency approach, compound 13 was further selected for radioiodination with iodine-125 and imaging experiments. Compound 13 showed its ability to displace the specific signal of the reference compound [125I]SB-207710 but no significant detection of [125I]13 was observed in vivo in SPECT experiments.

中文翻译：

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使用配体亲脂效率方法设计用于中枢人5-HT4R SPECT成像的碘化放射性配体。

从先前报道的命中MR-26132开始，设计了一系列用于5-HT4受体SPECT成像的碘化配体。我们致力于通过引入亲水基团来调节含哌啶的侧链，以降低新配体的亲脂性。测试所有合成的化合物在5-HT4Rs上的结合亲和力，并基于配体亲脂性效率方法，进一步选择化合物13用于碘125放射性碘化和成像实验。化合物13显示出取代参考化合物[125I] SB-207710的特定信号的能力，但是在SPECT实验中没有观察到体内对[125I] 13的显着检测。