Design of iodinated radioligands for SPECT imaging of central human 5-HT4R using a ligand lipophilicity efficiency approach.

Victor Babin, Benjamin B Tournier, Audrey Davis, Emmanuelle Dubost, Gilbert Pigrée, Jean-François Lohier, Vincent Reboul, Thomas Cailly, Jean-Philippe Bouillon, Philippe Millet, Frédéric Fabis

Bioorganic chemistry 2020 Mar

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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. Copyright © 2020 Elsevier Inc. All rights reserved.

Citation

Victor Babin, Benjamin B Tournier, Audrey Davis, Emmanuelle Dubost, Gilbert Pigrée, Jean-François Lohier, Vincent Reboul, Thomas Cailly, Jean-Philippe Bouillon, Philippe Millet, Frédéric Fabis. Design of iodinated radioligands for SPECT imaging of central human 5-HT4R using a ligand lipophilicity efficiency approach. Bioorganic chemistry. 2020 Mar;96:103582