Bivalent multifunctional ligands targeting Aβ oligomers as treatment for Alzheimer's disease
申请人:Zhang Shujin
公开号:US09260473B2
公开(公告)日:2016-02-16
Bivalent multifunctional Aβ oligomerization inhibitors (BMAOIs) that target multiple risk factors involved in Alzheimer's disease are provided. The BMAOIs are useful for the treatment and/or prevention of Alzheimer's disease, as well as for diagnostic imaging of Aβ plaques in brain tissue. The BMAOIs comprise i) an Aβ oligomer (ApO)-inhibitor moiety which may have antioxidant activity (e.g. curcumin, curcumin derivatives, curcumin hybrids, resveratrol, etc.); ii) a cell membrane/lipid raft (CM/LR) anchoring moiety (e.g. cholesterol, cholesterylamine, a steroid, etc.); and iii) a spacer or linker moiety that stably links i) and ii) together.
提供了针对多种涉及阿尔茨海默病的风险因素的双价多功能Aβ寡聚体化抑制剂(BMAOIs)。这些BMAOIs对于阿尔茨海默病的治疗和/或预防以及脑组织中Aβ斑块的诊断成像非常有用。这些BMAOIs包括i)一种Aβ寡聚体(ApO)抑制剂基团,可能具有抗氧化活性(例如姜黄素、姜黄素衍生物、姜黄素杂合物、白藜芦醇等);ii)一个细胞膜/脂质浮游(CM/LR)锚定基团(例如胆固醇、胆固醇胺、类固醇等);和iii)一个稳定连接i)和ii)的间隔或连接基团。