Polyfluorinated Bis-styrylbenzene -Amyloid Plaque Binding Ligands

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• 作者：Daniel P. Flaherty ; Shannon M. Walsh ; Tomomi Kiyota ; Yuxiang Dong ; Tsuneya Ikezu ; Jonathan L. Vennerstrom
• 刊名：Journal of Medicinal Chemistry
• 出版年：2007
• 出版时间：October 4, 2007
• 年：2007
• 卷：50
• 期：20
• 页码：4986 - 4992
• 全文大小：583K
• 年卷期：v.50,no.20(October 4, 2007)
• ISSN：1520-4804

文摘

-Amyloid (A) binding affinities and specificities for six bis-styrylbenzenes with multiple magneticallyequivalent fluorine atoms in the form of a tetrafluorophenyl core or symmetrical trifluoromethyl andtrifluoromethoxy groups were determined by means of fluorescence titrations with amyloid peptide A_1-40and a novel in vitro fluorescence-based assay using APP/PS1 transgenic mouse brain sections. Bis-styrylbenzenes with a tetrafluorophenyl core had increased A binding affinities compared to theirmonofluorophenyl or phenyl counterparts. Bis-styrylbenzenes with carboxylic acid functional groups hadlower A binding affinities than their neutral counterparts. Selected bis-styrylbenzenes were demonstratedto have good blood-brain barrier penetration capabilities. These data extend the SAR of bis-styrylbenzeneA binding and provide direction for the development of a noninvasive probe for early detection ofAlzheimer's disease using ¹⁹F MRI.