Polyfluorinated bis-styrylbenzene β-Amyloid plaque binding ligands

ss-Amyloid (A ss) binding affinities and specificities for six bis-styrylbenzenes with multiple magnetically equivalent fluorine atoms in the form of a tetrafluorophenyl core or symmetrical trifluoromethyl and trifluoromethoxy groups were determined by means of fluorescence titrations with amyloid peptide A ss(1-40) and a novel in vitro fluorescence-based assay using APP/PS1 transgenic mouse brain sections. Bis-styrylbenzenes with a tetrafluorophenyl core had increased A ss binding affinities compared to their monofluorophenyl or phenyl counterparts. Bis-styrylbenzenes with carboxylic acid functional groups had lower A ss binding affinities than their neutral counterparts. Selected bis-styrylbenzenes were demonstrated to have good blood-brain barrier penetration capabilities. These data extend the SAR of bis-styrylbenzene A ss binding and provide direction for the development of a noninvasive probe for early detection of Alzheimer's disease using F-19 MRI.