An efficient synthesis of the 3‐(6‐methoxy‐2‐naphtyl) 3‐methyl‐1,4‐diaryl‐2‐azetanone through changes on the main functional group of 2‐(6‐methoxy‐2‐naphthyl) propanoic acid is described. Formally, this transformation can be regarded as a [2+2]‐cycloaddition of aromatic imines with methyl naphthylketene generated in situ. To confirm ketene formation, the stable free radical TEMPO (TO•, 2,2,6,6‐Tetramethylpiperidinyloxy) was added to the reaction medium and the corresponding additive product was obtained, indicating the presence of this active intermediate in the reaction medium. This efficient method provides fast access to a variety of structurally diverse β‐lactam derivatives. Also, some new β‐lactam derivatives were evaluated for their anticonvulsant activity, as well as the impact of geometrical isomerism on their ability to interact with key residue of GABA_A receptor binding pocket in molecular docking studies. Experimental results revealed that between all, cis‐14 a seizure inhibition was done in a longer time in vivo especially in compare to diazepam. Also, in molecular docking studies, cis‐14 a matched with the shape of the GABA_A binding pocket which led to give the best position and lowest binding energy.

中文翻译：

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通过原位生成的酮酮进入拥挤的β-内酰胺萘普生环系统：合成，分子对接和抗惊厥活性评估

通过改变2-（6-甲氧基-2-萘基）丙酸的主要官能团，有效合成3-（6-甲氧基-2-萘基）3-甲基-1,4-二芳基-2-氮杂环丁酮描述。形式上，这变换可被认为是具有甲基naphthylketene生成芳香亚胺的[2 + 2] -环在 原位。为了确认烯酮的形成，将稳定的自由基TEMPO（TO•，2,2,6,6-四甲基哌啶基氧基）添加到反应介质中，并获得了相应的添加剂产物，表明该活性中间体存在于反应介质中。这种有效的方法可快速访问各种结构多样的β-内酰胺衍生物。此外，在分子对接研究中，评估了一些新的β-内酰胺衍生物的抗惊厥活性，以及​​几何异构对它们与GABA _A受体结合口袋的关键残基相互作用的能力的影响。实验结果表明，所有之间，顺式-14 一个发作抑制作用在更长的时间内完成在 体内特别是与地西epa相比。另外，在分子对接研究中，顺式‐ 14  a与GABA _A结合口袋的形状匹配，从而给出了最佳位置和最低结合能。