Due to the complex pathogenesis of AD, the multitarget-directed ligands (MTDLs) strategy presented the best pharmacological option for AD treatment. Herein, a series of novel 2-acetylphenol-O-alkylhydroxyethylamine derivatives (5a–f and 6a–f) was rationally designed and synthesized. Of these derivatives, 5c was a good multifunctional agent (eeAChE IC₅₀ = 7.9 μM, MAO-B IC₅₀ = 9.9 μM, BACE1 IC₅₀ = 8.3 μM) in vitro and displayed a mixed-type AChE inhibition, which could bind to the CAS and PAS of AChE. Compound 5c also exhibited good antioxidant activity (ORAC = 2.5 eq) and neuroprotective effects. Furthermore, compound 5c was a selective metal ions chelator. And it could cross blood–brain barrier in vitro and complied with drug-like properties rule of 5. Therefore, compound 5c was a promising multifunctional agent for the treatment of AD.

由于 AD 的复杂发病机制，多靶点定向配体 (MTDL) 策略是 AD 治疗的最佳药理学选择。在此，合理设计并合成了一系列新型 2-乙酰苯酚-O-烷基羟乙胺衍生物（5a - f和6a - f）。在这些衍生物中，5c 在体外是一种很好的多功能药物（ee AChE IC ₅₀  = 7.9 μM，MAO-B IC ₅₀  = 9.9 μM，BACE1 IC ₅₀ = 8.3 μM）并表现出混合型 AChE 抑制作用，可与AChE 的 CAS 和 PAS。化合物5c还表现出良好的抗氧化活性（ORAC = 2.5 eq）和神经保护作用。此外，化合物5c是一种选择性金属离子螯合剂。并且它可以在体外穿过血脑屏障，符合类药性规则5。因此，化合物5c是一种很有前途的治疗AD的多功能药物。