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Synthesis, crystal and molecular structure, vibrational spectroscopic, DFT study and activity evaluation of 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
  • +5
  • Qingmei Wu,
  • Wenjun Ye,
  • Qian Guo,
  • Tianhui Liao,
  • Weike Liao,
  • chunshen Zhao,
  • Huifang Chai,
  • Zhixu Zhou
Qingmei Wu
Guizhou University

Corresponding Author:[email protected]

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Wenjun Ye
Guizhou University
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Qian Guo
Guizhou University
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Tianhui Liao
Guizhou University
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Weike Liao
Guizhou Medical University
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chunshen Zhao
Guizhou University
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Huifang Chai
Guizhou University Of Traditional Chinese Medicine
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Zhixu Zhou
Guizhou University
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Abstract

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) by ring-opening, cyclization, substitution, doamine condensation and Mannich reactions. The structural properties of the title compound 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/6-311G (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/6-311G (2d, p) method. Molecular docking has shown favorable interaction between the title compound 1 and SHP2 protein. The inhibitory activity of target compound 1 on SHP2 protein at 10 μM is better than the reference compound (SHP244).