69857-33-6Relevant articles and documents
Flexible multidentate benzyldiamine derivatives with high affinity for β-amyloid in cerebral amyloid angiopathy
He, Yujia,Fu, Tingting,Li, Yuying,Xue, Weiwei,Cui, Mengchao,Wang, Liang,Niu, Mengda,Peng, Zhiping,Jia, Jianhua
, p. 525 - 533 (2020/05/25)
Abstract: Cerebral amyloid angiopathy (CAA) commonly found in the aged is pathologically characterized by β-amyloid (Aβ) deposition in the walls of arteries and capillaries of brain. In this study, four flexible multidentate benzyldiamine derivatives as potential probes for cerebrovascular Aβ deposition were designed and synthesized. In in vitro inhibition assays, the ligands 18–21 displayed high affinities for Aβ aggregates with Ki values of 1.45 ± 0.53?nM, 1.68 ± 0.35?nM, 1.16 ± 0.23?nM and 1.72 ± 0.19?nM, respectively. A significant improvement in the binding affinity over the monomer, compounds 9–12 or benzyldiamine derivatives, demonstrated the applicability of the multidentate approach. The underlying mechanism of these novel Aβ agents was explored by molecular docking technique, which theoretically verified the high affinities of the multidentate benzyldiamine derivatives for Aβ aggregates. Moreover, the molecular masses of the ligands 18–21 are more than 700 Dalton, which are believed to be hardly capable of penetrating blood brain barrier. In this regard, these ligands could be used to distinguish CAA from Alzheimer’s disease which is another Aβ-related disorder disease. To convert these ligands to positron emission tomography imaging agents, we attempted to radiosynthesize [18F]18. Though the radiolabeling was not very successful, the preliminary results suggested that these newly proposed multidentate benzyldiamine derivatives may be used as potential Aβ imaging agents in cerebral amyloid angiopathy. Graphic abstract: [Figure not available: see fulltext.].
Polyfluorinated bis-styrylbenzene β-amyloid plaque binding ligands
Flaherty, Daniel P.,Walsh, Shannon M.,Kiyota, Tomomi,Dong, Yuxiang,Ikezu, Tsuneya,Vennerstrom, Jonathan L.
, p. 4986 - 4992 (2008/03/12)
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.
