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Article Dans Une Revue European Journal of Medicinal Chemistry Année : 2015

Design of a serotonin 4 receptor radiotracer with decreased lipophilicity for single photon emission computed tomography

Résumé

With the aim to develop a suitable radiotracer for the brain imaging of the serotonin 4 receptor subtype (5-HT4R) using single photon emission computed tomography (SPECT), we synthesized and evaluated a library of di- and triazaphenanthridines with lipophilicity values which were in the range expected to favour brain penetration, and which demonstrated specific binding to the target of interest. Adding additional nitrogen atoms to previously described phenanthridine ligands exhibiting a high unspecific binding, we were able to design a radioiodinated compound [125I]14. This compound exhibited a binding affinity value of 0.094 nM toward human 5-HT4R and a high selectivity over other serotonin receptor subtypes (5-HTR). In vivo SPECT imaging studies and competition experiments demonstrated that the decreased lipophilicity (in comparison with our previously reported compounds 4 and 5) allowed a more specific labelling of the 5-HT4R brain-containing regions.
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Dates et versions

hal-02011103 , version 1 (07-02-2019)

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Nathalie Fresneau, Noé Dumas, Benjamin B. Tournier, Christine Fossey, Céline Ballandonne, et al.. Design of a serotonin 4 receptor radiotracer with decreased lipophilicity for single photon emission computed tomography. European Journal of Medicinal Chemistry, 2015, 94, pp.386-396. ⟨10.1016/j.ejmech.2015.03.017⟩. ⟨hal-02011103⟩
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