110193-90-3Relevant articles and documents
Discovery of Diphenoxy Derivatives with Flexible Linkers as Ligands for β-Amyloid Plaques
Jia, Jianhua,Zhang, Longfei,Song, Jia,Dai, Jiapei,Cui, Mengchao
, p. 4089 - 4100 (2020/12/13)
The highly rigid and planar scaffolds with π-conjugated systems have been widely considered to be indispensable for β-amyloid (Aβ) binding ligands. In this study, a library of diphenoxy compounds with different types of more flexible linkers as Aβ ligands were synthesized and evaluated. Most of them displayed good affinity (Ki1-42aggregates, and some ligands even showed values of Kiless than 10 nM. Structure-activity relationship analysis revealed that modification on the linkers or substituents tolerated great flexibility, which challenged the long-held belief that rigid and planar structures are exclusively favored for Aβ binding. Three ligands were labeled by iodine-125, and they exhibited good properties in vitro and in vivo, which further supported that this flexible scaffold was potential and promising for the development of Aβ imaging agents.
