Abstract In this research article we report a simple protocol for the synthesis of series novel of substituted (Z)-3-benzylidine-5-aza-2-oxindole derivatives (5a-f) by employing optimized reaction condition of Knoevenagel condensation. Among the reaction conditions attempted, the reaction in ethanol and piperidine at 80 °C afforded the desired products (5a-f) in satisfactory yields and enhanced purity via trituration and recrystallization. The physicochemical as well as spectroscopic evidences established the assigned structures of the compounds without any ambiguity. The anti-inflammatory proficiency assessment for the synthesized compounds has been carried out on the basis of Prediction of Activity Spectra for Substances (PASS) technique and compared with standard tenidap. Furthermore, to validate the results of PASS prediction, molecular docking studies of the synthesized compounds (5a-f) were carried out on the TNF-α target protein (PDB ID: 2AZ5 ). The compounds displayed less docking energies in the range of -6.9 to -7.5 Kcal/mol than tenidap (-8.8 Kcal/mol). Additionally, in silico ADME analysis was carried out to check drug ability and toxicity issues.

中文翻译：

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取代-(Z)-3-benzylidine-5-aza-2-oxindole 衍生物的设计、合成、PASS 预测、In-silico ADME 和分子对接研究（第 1 部分）

摘要 在这篇研究文章中，我们报告了通过采用优化的 Knoevenagel 缩合反应条件合成系列新型取代 (Z)-3-benzylidine-5-aza-2-oxindole 衍生物 (5a-f) 的简单方案。在尝试的反应条件中，乙醇和哌啶在 80°C 下的反应以令人满意的收率和通过研磨和重结晶提高纯度提供了所需的产物 (5a-f)。物理化学和光谱证据确定了化合物的指定结构，没有任何歧义。基于物质活性谱预测（PASS）技术并与标准替尼达进行了比较，对合成化合物的抗炎能力进行了评估。此外，为了验证 PASS 预测的结果，在 TNF-α 靶蛋白（PDB ID：2AZ5）上进行了合成化合物（5a-f）的分子对接研究。与tenidap (-8.8 Kcal/mol) 相比，这些化合物在-6.9 至-7.5 Kcal/mol 的范围内显示出更少的对接能量。此外，还进行了计算机 ADME 分析以检查药物能力和毒性问题。