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

Victor Babin (1) , Benjamin B. Tournier (2) , Audrey Davis (1) , Emmanuelle Dubost (1) , Gilbert Pigrée (3) , Jean-François Lohier (4) , Vincent Reboul (4) , Thomas Cailly (1) , J.-P. Bouillon (5) , Philippe Millet (2) , Frédéric Fabis (1)

1 CERMN - Centre d'Etudes et de Recherche sur le Médicament de Normandie
2 HUG - Geneva University Hospital
3 IMOGERE - Installations de Mise en Oeuvre et de GEstion des Radioéléments [Caen]
4 LCMT - Laboratoire de chimie moléculaire et thioorganique
5 COBRA - Chimie Organique et Bioorganique : Réactivité et Analyse

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.

Domains: Chemical Sciences

Victor Babin, Benjamin B. Tournier, Audrey Davis, Emmanuelle Dubost, Gilbert Pigrée, et al.. Design of iodinated radioligands for SPECT imaging of central human 5-HT4R using a ligand lipophilicity efficiency approach. Bioorganic Chemistry, 2020, 96, pp.103582. ⟨10.1016/j.bioorg.2020.103582⟩. ⟨hal-02466870⟩