Labeling of benzodioxin piperazines with fluorine‐18 as prospective radioligands for selective imaging of dopamine D4 receptors

The D₄ 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 D₄ 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 D₄ 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 ¹⁸F‐labeling and build‐up synthesis were compared. All derivatives of 6‐(4‐[4‐fluorobenzyl]‐piperazin‐1‐yl)benzodioxin were successfully synthesized in ¹⁸F‐labeled form with radiochemical yields of 9–35% and molar activities of 30–60 GBq/µmol using one‐pot procedures. Copyright © 2013 John Wiley & Sons, Ltd.