11C-Labeling of N-[4-[4-(2,3-Dichlorophenyl)piperazin-1-yl]butyl]arylcarboxamide Derivatives and Evaluation as Potential Radioligands for PET Imaging of Dopamine D3 Receptors
| Autor: | Francesco Berardi, Mario Matarrese, Marzia Galli Kienle, Fulvio Magni, Sara Belloli, Rosa Mafia Moresco, Pasquale Simonelli, Enza Lacivita, Ferruccio Fazio, Nicola Antonio Colabufo, Roberto Perrone, Marcello Leopoldo, E. Turolla, Sergio Todde |
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| Přispěvatelé: | Turolla, E, Matarrese, M, Belloli, S, Moresco, R, Simonelli, P, Todde, S, Fazio, F, Magni, F, Kienle, M, Leopoldo, M, Berardi, F, Colabufo, N, Lacivita, E, Perrone, R |
| Rok vydání: | 2005 |
| Předmět: |
Male
Biodistribution Carbonio-11 Stereochemistry autoradiografia Ligands Chemical synthesis Piperazines Structure-Activity Relationship chemistry.chemical_compound Dopamine receptor D3 In vivo Drug Discovery Radioligand Animals Tissue Distribution Carbon Radioisotopes Dopamine D3 Receptors radiochemistry Bicyclic molecule Dopamina D3 Radiochemistry Radiosynthesis Receptors Dopamine D3 Brain Amides neurodegenerazione Rats PET chemistry Blood-Brain Barrier Positron-Emission Tomography Autoradiography Molecular Medicine Radiopharmaceuticals Methyl iodide |
| Zdroj: | Journal of medicinal chemistry 48 (2005): 7018–7023. doi:10.1021/jm050171k info:cnr-pdr/source/autori:Turolla E.A 1., Matarrese M. 1, Belloli S. 1, Moresco R.M. 1, Simonelli P. 1, Todde S. 1, Fazio F. 1, Magni F. 2, Galli Kienle M. 2, Leopoldo M. 3, Berardi F. 3, Colabufo N.A. 3, Lacivita E. 3, Perrone R. 3/titolo:11C-Labelling of N-[4-[4-(2,3-dichlorophenyl)piperazin-1-yl]butyl]arylcarboxamide derivatives and evaluation as potential radioligands for PET imaging of dopamine D3 receptors/doi:10.1021%2Fjm050171k/rivista:Journal of medicinal chemistry/anno:2005/pagina_da:7018/pagina_a:7023/intervallo_pagine:7018–7023/volume:48 |
| ISSN: | 1520-4804 0022-2623 |
| Popis: | The selective dopamine D(3) receptor ligands N-4-[4-[(2,3-dichlorophenyl)piperazin-1-yl]butyl]1-methoxy-2-naphthalencarboxamide (1) and N-4-[4-[(2,3-dichlorophenyl)piperazin-1-yl]butyl]-7-methoxy-2-benzofurancarboxamide (2) were labeled with (11)C (t(1/2) = 20.4 min) as potential radioligands for the noninvasive assessment of the dopamine D(3) neurotransmission system in vivo with positron emission tomography (PET). The radiosynthesis consisted in an O-methylation of the des-methyl precursors N-[4-[4-(2,3-dichlorophenyl)piperazin-1-yl]butyl]-1-hydroxy-2-naphthalenecarboxamide (3) and N-[4-[4-(2,3-dichlorophenyl)piperazin-1-yl]butyl]-7-hydroxy-2-benzofurancarboxamide (4) with [(11)C]methyl iodide using tBuOK/HMPA and KOH/DMSO, respectively. The radiotracers [(11)C]1 and [(11)C]2 were obtained in 35 min with over 99% radiochemical purity, 74 +/- 37 GBq/mumol of specific radioactivity, 13% and 26% radiochemical yield (EOB, decay-corrected). Distribution studies in rats demonstrated that the new tracers [(11)C]1 and [(11)C]2 cross the blood-brain barrier and localize in the brain. However, the kinetics of cerebral uptake did not reflect the regional expression of the D(3) receptors. Despite their in vitro pharmacological profile, [(11)C]1 and [(11)C]2 do not display an in vivo behavior suitable to image D(3) receptor expression using PET. |
| Databáze: | OpenAIRE |
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