期刊
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
卷 246, 期 -, 页码 -出版社
ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
DOI: 10.1016/j.ejmech.2022.114991
关键词
Alzheimer?s disease; Tau tangles; Radiotracer; Autoradiography
In this study, a series of new aza-fused tricyclic derivatives were designed and synthesized. The imidazonaphthyridine scaffold was screened and reported for the first time, which has the potential to detect Tau aggregates. Probe [125I]5 showed exceptional binding affinity to neurofibrillary tangles in the AD brain, high selectivity over A beta plaques, clean off-target profile to MAO-A/B, and suitable pharmacokinetics.
For various neurodegenerative diseases, including Alzheimer's disease (AD), the abnormal aggregation of Tau is not only the predominant contributing factor but also a major biomarker for disease diagnosis. In this study, a series of aza-fused tricyclic derivatives were designed and synthesized. By changing the position and number of nitrogen atoms on the fused tricyclic core, the imidazonaphthyridine scaffold was screened and reported for the first time which could potentially detect Tau aggregates. Through a series of in vitro and in vivo biological evaluations, probe [125I]5 possessed exceptional binding affinity (IC50 = 1.63 nM) to neurofibrillary tangles in the AD brain, high selectivity over A beta plaques (23.4-fold), clean off-target profile to monoamine oxidase A/B (MAO-A/B), and suitable pharmacokinetics (initial brain uptake = 3.22% ID/g).
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据