In current work, we have firstly synthesized 4-(2-chlorobenzyl)-1-(4‑hydroxy-3- ((4-hydroxypiperidin-1-yl)methyl)-5-methoxyphenyl)-[1,2,4]triazolo[4,3-a]quinazolin-5(4H)-one (1). The structural properties of 1 were explored using spectroscopy (¹H NMR, ¹³C NMR, MS and FT-IR) and X-ray crystallography method. The single-crystal structure confirmed by X-ray diffraction was consistent with the molecular structure optimized by density functional theory (DFT) calculation at B3LYP/6–311 G (2d, p) level of theory. The geometrical parameters, molecular electrostatic potential (MEP) and frontier molecular orbital (FMO) analysis were performed by DFT using the B3LYP/6–311 G (2d, p) method. Molecular docking may suggest a favorable interaction between 1 and SHP2 protein. The molecular dynamics (MD) simulation results shown that there are hydrogen bonds, electrostatic interactions and Pi interactions between compound 1 and SHP2 proteins. The inhibitory activity of 1 on SHP2 protein at 10 μM is better than the reference compound (SHP244).

在目前的工作中，我们首先合成了4-（2-氯苄基）-1-（4-羟基-3-（（4-羟基哌啶-1-基）甲基）-5-甲氧基苯基）-[1,2,4]三唑并[4,3 - a ]quinazolin-5(4 H )-one ( 1 )。的结构性质1使用光谱（进行了探索¹ H NMR，¹³C NMR、MS 和 FT-IR) 和 X 射线晶体学方法。通过 X 射线衍射证实的单晶结构与在 B3LYP/6-311 G (2d, p) 理论水平下通过密度泛函理论 (DFT) 计算优化的分子结构一致。几何参数、分子静电势 (MEP) 和前沿分子轨道 (FMO) 分析通过 DFT 使用 B3LYP/6-311 G (2d, p) 方法进行。分子对接可能表明1和 SHP2 蛋白之间存在有利的相互作用。分子动力学(MD)模拟结果表明，化合物1与SHP2蛋白之间存在氢键、静电相互作用和Pi相互作用。1的抑制活性10 μM 对 SHP2 蛋白的影响优于参考化合物 ( SHP244 )。