title: Labeling of benzodioxin piperazines with fluorine-18 as prospective radioligands for selective imaging of dopamine D4 receptors.
abstract: The D(4) receptor is of high interest for research and clinical application but puts high demands on appropriate radioligands to be useful tools for investigation. Search for adequate radioligands suitable for in vivo imaging is therefore still in progress. The potential neuroleptic drug 6-(4-[4-fluorobenzyl]piperazin-1-yl)benzodioxin shows high affinity and selectivity to the D(4) receptor. Derivatization of this lead structure by adding hydrophilic moieties was carried out in order to lower its lipophilicity what led to three new putative dopamine receptor D(4) ligands. A comprehensive description of the syntheses of standard compounds and corresponding labeling precursors is given which were obtained in satisfactory yields. Furthermore, the radiosyntheses by direct (18) F-labeling and build-up synthesis were compared. All derivatives of 6-(4-[4-fluorobenzyl]-piperazin-1-yl)benzodioxin were successfully synthesized in (18) F-labeled form with radiochemical yields of 9-35% and molar activities of 30-60 GBq/µmol using one-pot procedures.
authors.affiliation: Institute of Neurosciences and Medicine, INM-5: Nuclear Chemistry, Forschungszentrum Jülich GmbH, Jülich, Germany; Present address: Nuklearmedizinische Klinik und Poliklinik, Technische Universität München, Ismaninger Straße 22, D-81675, München, Germany.
authors.forename: Fabian
authors.initials: F
authors.lastname: Kügler
authors.forename: Johannes
authors.initials: J
authors.lastname: Ermert
authors.forename: Heinz H
authors.initials: HH
authors.lastname: Coenen
mesh_terms: D015259:Dopamine Agents / Q000138:chemical synthesis*; D005462:Fluorine Radioisotopes / Q000737:chemistry*; D007553:Isotope Labeling; D008024:Ligands; D010879:Piperazines / Q000138:chemical synthesis*; D019275:Radiopharmaceuticals / Q000138:chemical synthesis*; D050638:Receptors, Dopamine D4 / Q000032:analysis
chemical_list: D015259:Dopamine Agents; D005462:Fluorine Radioisotopes; D008024:Ligands; D010879:Piperazines; D019275:Radiopharmaceuticals; D050638:Receptors, Dopamine D4
keywords: dopamine D4 receptor; n.c.a. [18F]fluoride; one-pot radiosynthesis; positron emission tomography; radioligand