As Alzheimer disease (AD) is a multifactorial condition, it should be tackled with drugs targeting multiple key pathways. A series of aliphatic (2–8) and aromatic (9–15) edaravone derivatives were synthesized, characterized, and evaluated as antioxidant agents using 1,1-diphenyl-2-picrylhydrazyl (DPPH) and 2-2’-azino-bis-(3-ethylbenzothiazoline-6-sulfonate) (ABTS·⁺) assays, as well as acetylcholinesterase (AChE) inhibitors. In both antioxidant assays, even though the starting compound edaravone was more active, the best derivative was 5 with 50% effective concentration (EC₅₀) of 0.0301 and 0.8106 mM respectively, followed by 3 (EC₅₀ of 0.1920 mM and 3.5311 mM). In the AChE inhibition assay, the derivatives were not as active as the positive control galantamine, but a general better activity was shown from the aromatic compounds. The best results were for 10, with 41.9% of inhibition (concentration of 150 μg/mL), and 9 with 31.6%. Docking analysis of compound 10 showed hydrogen bonds with residues Ser200 and His440 in the AChE catalytic gorge. All synthesized derivatives 2–15 presented drug-like properties and are capable of crossing the blood–brain barrier and not be pumped out of it. These results indicate edaravone derivatives can function as scaffolds for AD drugs, though further derivatizations should be conducted to improve their antioxidant and AChE inhibition profiles.

由于阿尔茨海默氏病（AD）是多因素疾病，因此应使用针对多种关键途径的药物来解决。一系列脂族（的2 - 8）和芳族（9 - 15）依达拉奉衍生物的合成，其特征在于，并用1,1-二苯基-2-苦基苯肼（DPPH）和2,2'-连氮基-双作为抗氧化剂评价-（3-乙基苯并噻唑啉-6-磺酸盐）（ABTS· ⁺）测定法，以及乙酰胆碱酯酶（AChE）抑制剂。在两种抗氧化剂测定中，即使起始化合物依达拉奉具有更高的活性，最佳衍生物为5，其50％有效浓度（EC ₅₀）分别为0.0301和0.8106 mM，然后为3（EC0.1920 mM和3.5311 mM中的₅₀）。在AChE抑制试验中，衍生物的活性不如阳性对照加兰他敏，但芳香族化合物的活性通常更高。最佳结果为10，抑制率为41.9％（浓度为150μg/ mL），9为31.6％。化合物10的对接分析显示AChE催化峡谷中的残基Ser200和His440具有氢键。所有合成衍生物2 – 15具有类似药物的特性，能够穿过血脑屏障并且不会被泵出。这些结果表明依达拉奉衍生物可以用作AD药物的支架，尽管应该进一步衍生化以改善其抗氧化剂和AChE抑制作用。