N-2-(4-N-(4-[18F]Fluorobenzamido)phenyl)-propyl-2-propanesulphonamide: synthesis and radiofluorination of a putative AMPA receptor ligand

Arylpropylsulphonamides are in the focus of research as α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolpropionic acid (AMPA) receptor ligands. A new fluorine‐18‐labelled potentiator of AMPA receptors was synthesized as a potential radiotracer for cerebral imaging with positron emission tomography. Using N‐2‐(4‐N‐(4‐nitrobenzamido)phenyl)‐propyl‐2‐propanesulphonamide (7) as labelling precursor for a Kryptofix 2.2.2®/K2CO3‐activated nucleophilic radiofluorination, the putative AMPA receptor ligand N‐2‐(4‐N‐(4‐[18F]fluorobenzamido)phenyl)‐propyl‐2‐propanesulphonamide [18F]8 was obtained in one step. Optimization of the reaction parameters time, temperature, solvent and concentration gave a radiochemical yield of 38±8% at 180°C in dimethylsulphoxide within 30‐min reaction time. After a solid‐phase extraction followed by a high‐performance liquid chromatography separation, the product could be obtained in radiochemical yields of 5±1.5%. Radiochemical purity was higher than 95% and the specific activity amounted to 77±40 GBq/µmol. First in vitro assays with rat brain slices revealed a high non‐specific binding and a uniform distribution of [18F]8 not lending it for in vivo imaging purposes. Copyright © 2007 John Wiley & Sons, Ltd. Synthesis of a benzamide as precursor for labelling with fluorine‐18. Radiofluorination achieved by [18F]fluoride‐for‐nitro exchange and reaction conditions were optimized. Copyright © 2007 John Wiley & Sons, Ltd.