Synthesis, crystal and molecular structure, vibrational spectroscopic, DFT and molecular docking 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

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 (H-1 NMR, C-13 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 mu M is better than the reference compound (SHP244). (C) 2021 Elsevier B.V. All rights reserved.

Automated summary

In this study, a new compound was synthesized and characterized using spectroscopy, X-ray crystallography, and computational chemistry methods. The results demonstrated potential inhibitory activity of the compound on the SHP2 protein, suggesting promising applications in drug development.