Novel N-phenethyl-2-(1H-1,2,3-triazol-1-yl)acetamide derivatives were synthesized via Copper(I)-catalyzed 1,3-dipolar azide-alkyne cycloaddition, commonly known as CuAAC. These triazoles were then characterized using Nuclear Magnetic Resonance (NMR), Fourier Transform Infrared Spectroscopy (FTIR), and Mass Spectrometry (MS). The crystal structures of ten compounds were elucidated through single-crystal X-ray diffraction (SCXRD). Computational calculations, based on Density Functional Theory (DFT), were employed to optimize the molecular structures. The energy levels of the highest occupied molecular orbital (HOMO) and the lowest unoccupied molecular orbital (LUMO) were also determined. Additionally, molecular docking studies revealed the binding interactions of the most potent triazole with the active sites of key molecular targets. The findings indicated that the newly synthesized triazoles exhibit promising inhibitory activity against SARS-CoV-2 proteases 3-chymotrypsin-like protease (3CLpro), papain-like protease (PLpro), and helicase, outperforming the co-crystallized ligand.

中文翻译：

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N-苯乙基-2-（1H-1,2,3-三唑-1-基）乙酰胺衍生物：针对 SARS-CoV-2 的合成、晶体结构和分子对接研究


新型 N-苯乙基-2-（1H-1,2,3-三唑-1-基）乙酰胺衍生物是通过铜 （I） 催化的 1,3-偶极叠氮化物-炔烃环加成反应（俗称 CuAAC）合成的。然后使用核磁共振 （NMR）、傅里叶变换红外光谱 （FTIR） 和质谱 （MS） 对这些三唑进行表征。通过单晶 X 射线衍射 （SCXRD） 阐明了 10 种化合物的晶体结构。基于密度泛函理论 （DFT） 的计算计算用于优化分子结构。还测定了最高占据分子轨道 （HOMO） 和最低未占据分子轨道 （LUMO） 的能级。此外，分子对接研究揭示了最有效的三唑与关键分子靶标活性位点的结合相互作用。结果表明，新合成的三唑类药物对 SARS-CoV-2 蛋白酶 3-胰凝乳蛋白酶样蛋白酶 （3CLpro）、木瓜蛋白酶样蛋白酶 （PLpro） 和解旋酶表现出有希望的抑制活性，优于共结晶配体。