In this study, a total of 18 new benzamide/ nicotinamide/ cinnamamide derivative compounds were designed and synthesized for the first time (except B1 and B5) by conventional and microwave irradiation methods. The chemical structures of the synthesized compounds were characterized by ¹H NMR, ¹³C NMR, and HRMS spectra. In vitro acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibition effects of the compounds were evaluated to find out new possible drug candidate molecule/s. According to the inhibition results, the IC50 values of the compounds synthesized were in the range of 10.66–83.03 nM towards AChE, while they were in the range of 32.74–66.68 nM towards BuChE. Tacrine was used as the reference drug and its IC50 values were 20.85 nM and 15.66 nM towards AChE and BuChE, respectively. The most active compounds B4 (IC50: 15.42 nM), N4 (IC50: 12.14 nM), and C4 (IC50: 10.67 nM) in each series towards AChE were docked at the binding site of AChE enzyme to explain the inhibitory activities of each series. On the other hand, the compounds B4, N4, and C4 showed satisfactory pharmacokinetic properties via the prediction of ADME profiles.

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中文翻译：

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新的苯甲酰胺衍生物及其烟酰胺/肉桂酰胺类似物作为胆碱酯酶抑制剂

本研究通过常规和微波辐照方法，首次设计合成了18个苯甲酰胺/烟酰胺/肉桂酰胺新衍生物化合物（B1和B5除外）。合成化合物的化学结构通过¹ H NMR、¹³C NMR和HRMS光谱。评估了化合物的体外乙酰胆碱酯酶 (AChE) 和丁酰胆碱酯酶 (BuChE) 抑制作用，以找出新的可能的候选药物分子。根据抑制结果，合成的化合物对AChE的IC50值在10.66-83.03 nM范围内，而对BuChE的IC50值在32.74-66.68 nM范围内。他克林用作参比药物，其对 AChE 和 BuChE 的 IC50 值分别为 20.85 nM 和 15.66 nM。各系列对乙酰胆碱酯酶活性最强的化合物B4（IC50：15.42 nM）、N4（IC50：12.14 nM）和C4（IC50：10.67 nM）对接在AChE酶的结合位点，解释各系列的抑制活性. 另一方面，化合物 B4、N4、

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