Abstract
β-Amyloid (Aβ) 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 Aβ1-40 and a novel in vitro fluorescence-based assay using APP/PS1 transgenic mouse brain sections. Bisstyrylbenzenes with a tetrafluorophenyl core had increased Aβ binding affinities compared to their monofluorophenyl or phenyl counterparts. Bis-styrylbenzenes with carboxylic acid functional groups had lower Aβ 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 Aβ binding and provide direction for the development of a noninvasive probe for early detection of Alzheimer's disease using 19F MRI.
Original language | English (US) |
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Pages (from-to) | 4986-4992 |
Number of pages | 7 |
Journal | Journal of Medicinal Chemistry |
Volume | 50 |
Issue number | 20 |
DOIs | |
State | Published - Oct 20 2007 |
ASJC Scopus subject areas
- Molecular Medicine
- Drug Discovery