Design of a serotonin 4 receptor radiotracer with decreased lipophilicity for single photon emission computed tomography
| Autor: | Céline Ballandonne, Frédéric Fabis, Noé Dumas, Philippe Millet, Aurélien Lesnard, Christine Fossey, Jean-Philippe Bouillon, Benjamin B. Tournier, Yves Charnay, Nathalie Fresneau, Thomas Cailly |
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| Přispěvatelé: | Chimie Organique et Bioorganique : Réactivité et Analyse (COBRA), Institut Normand de Chimie Moléculaire Médicinale et Macromoléculaire (INC3M), Institut de Chimie du CNRS (INC)-École Nationale Supérieure d'Ingénieurs de Caen (ENSICAEN), Normandie Université (NU)-Normandie Université (NU)-Institut national des sciences appliquées Rouen Normandie (INSA Rouen Normandie), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Université Le Havre Normandie (ULH), Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS)-Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Institut de Chimie du CNRS (INC)-École Nationale Supérieure d'Ingénieurs de Caen (ENSICAEN), Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie Organique Fine (IRCOF), Université de Rouen Normandie (UNIROUEN), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Hôpitaux Universitaires de Genève (HUG), Centre d'Etudes et de Recherche sur le Médicament de Normandie (CERMN), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU) |
| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
Serotonin
Stereochemistry 5-HT Molecular imaging [CHIM.THER]Chemical Sciences/Medicinal Chemistry Single-photon emission computed tomography Ligands Iodine Radioisotopes 03 medical and health sciences chemistry.chemical_compound Structure-Activity Relationship ddc:616.89 0302 clinical medicine In vivo Spect imaging Drug Discovery medicine Humans 5-HT receptor 030304 developmental biology Pharmacology Tomography Emission-Computed Single-Photon 0303 health sciences Phenanthridine medicine.diagnostic_test Dose-Response Relationship Drug Molecular Structure Organic Chemistry Brain General Medicine 3. Good health Phenanthridines chemistry Drug Design SPECT Lipophilicity Biophysics Receptors Serotonin 5-HT4 Radiopharmaceuticals 030217 neurology & neurosurgery Radiolabeling Iodine |
| Zdroj: | European Journal of Medicinal Chemistry European Journal of Medicinal Chemistry, Elsevier, 2015, 94, pp.386-396. ⟨10.1016/j.ejmech.2015.03.017⟩ European Journal of Medicinal Chemistry, Vol. 94 (2015) pp. 386-96 |
| ISSN: | 0223-5234 1768-3254 |
| DOI: | 10.1016/j.ejmech.2015.03.017⟩ |
| Popis: | International audience; 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. |
| Databáze: | OpenAIRE |
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