A series of LX2343 derivatives were designed, synthesized and evaluated as neuroprotective agents for Alzheimer's disease (AD) in vitro. Most of the compounds displayed potent neuroprotective activities. Especially for compound A6, exhibited a remarkable EC₅₀ value of 0.22 μM. Further investigation demonstrated that compound A6 can significantly reduce Aβ production and increase Aβ clearance, and alleviate Tau hyperphosphorylation. Most importantly, compound A6 could ameliorate learning and memory impairments in APP/PS1 transgenic mice. The present study evidently showed that compound A6 is a potent neuroprotective agent and might serve as a promising lead candidate for the treatment of Alzheimer's disease.

设计，合成和评估了一系列LX2343衍生物作为体外阿尔茨海默氏病（AD）的神经保护剂。大多数化合物显示出有效的神经保护活性。特别是对于化合物A6，其EC ₅₀值显着为0.22μM。进一步的研究表明，化合物A6可以显着降低Aβ的产生并增加Aβ的清除，并减轻Tau的过度磷酸化。最重要的是，化合物A6可以改善APP / PS1转基因小鼠的学习和记忆障碍。本研究显然表明化合物A6 是有效的神经保护剂，可以作为治疗阿尔茨海默氏病的有希望的主要候选药物。