- Synthesis, crystal structure, and density functional theory study of a new compound 4-(2-chlorobenzyl)-1-(5-fluoro-2-hydroxy-3-(thiomorpholinomethyl)phenyl [1,2,4]triazolo[4,3-a]quinazolin-5(4H)-one
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In this paper, a novel SHP244 derivative 4-(2-chlorobenzyl)-1- (5-fluoro-2-hydroxy-3- [thiomorph-olinomethyl] phenyl)- [1,2,4]triazolo [4,3-a] quinazolin-5(4H)-one was synthesized through five steps. The single crystals were grown in a suitable solvent system (dichloromethane and methanol). Its structure was confirmed by 1H NMR, 13C NMR spectroscopy, ESI-MS, m/z: 534.12[M-H] (MS), FT-IR, and X-ray single crystal diffraction. The crystal structure of the title compound was optimized by density functional theory (DFT) calculation. The crystal structure after X-ray single crystal diffraction was compared with the structure optimized by DFT calculation, and the result shows that the two structures are consistent. In order to explore certain physical and chemical properties, the frontier molecular orbital and molecular electrostatic potential of the title compound were analyzed. In addition, the docking of the title compound to the target protein was studied to understand the docking effect of the compound with the target protein.
- Hu, Weiyin,Liao, Tianhui,Deng, Liyuan,Sun, Hong,Zhou, Zhixu,Chai, Huifang,Zhao, Chunshen
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- 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
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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 (1/sup
- Chai, Huifang,Guo, Qian,Liao, Tianhui,Liao, Weike,Wu, Qingmei,Yang, Di,Ye, Wenjun,Zhao, Chunshen,Zheng, Zhaopeng,Zhou, Zhixu
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- SYNTHESIS, CRYSTAL STRUCTURE, AND DFT STUDY OF 4-(2-CHLOROBENZYL)-1-(5-NITRO-2-(PYRROLIDIN-1-YL)PHENYL)- [1,2,4]TRIAZOLO[4,3-a]QUINAZOLIN-5(4H)-ONE
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Abstract: 4-(2-Chlorobenzyl)-1-(5-nitro-2-(pyrrolidin-1-yl)phenyl)-[1,2,4]triazolo[4,3-a]quinazo-lin-5(4H)-one is a derivative of quinazolinones with antitumor, antibacterial, anti-inflammatory, and antimicrobial effects. Using diabetic jujube as a raw material, the title compound is synthesized by substitution and cyclization steps. The structure of the target compound is confirmed by FTIR, 1H and 13C NMR, and MS spectroscopies. The precise structure of the 4-(2-chlorobenzyl)-1-(5-nitro-2-(pyrrolidin-1-yl)phenyl)-[1,2,4]triazolo[4,3-a]quinazolin-5(4H)-one compound is analyzed by single crystal X-ray diffraction (XRD). The molecular structure is further calculated using density functional theory (DFT) and the result is compared with the XRD value. The molecular electrostatic potential and frontier molecular orbitals of the title compound are investigated using DFT. In addition, the obtained atomic coordinates for the single crystal of the compound are then applied in a molecular docking simulation, and the title compound is found to participate in a number of important binding interactions in the SHP2 binding sites.
- Huang, P.-Y.,Liao, W.-K.,Liu, Y.,Ren, Q.,Zhao, C.-S.,Zhou, Z.-X.
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p. 1472 - 1482
(2021/11/03)
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- Design, synthesis, and biological evaluation of novel triazoloquinazolinone derivatives as SHP2 protein inhibitors
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A novel series of triazoloquinazolinone derivatives were designed, synthesised, and evaluated for their in vitro biological activities against the SHP2 protein. Moreover, some compounds were evaluated against A375 cells. The results revealed that target compounds possessed moderate to excellent inhibitory activity against SHP2 protein, whereas compounds 12f, 12l, 12j, 17e, and 17f have strong antiproliferative activity on A375 cells. The compound 12l showed remarkable cytotoxicity against A375 cells and a strong inhibitory effect against SHP2 protein when compared with SHP244. The structure-activity relationships (SARs) indicated that electron-donating groups (EDGs) on phenyl rings are beneficial for improving the antitumor activity; compounds with a hydroxyl substituent at the 2-position of phenyl ring exhibited superior activities than compounds with a substituent at the 4-position. In addition, compound 12l displayed improved physicochemical properties as well as metabolic stability compared to SHP244. Our efforts identified 12l as a promising SHP2 protein inhibitor, warranting its further investigation.
- Huang, Zhuyan,Lu, Tian,Luo, Dali,Luo, Rongshuang,Qin, Yumei,Wang, Zhongyuan,Yang, Di,Zhao, Chunshen,Zhou, Zhixu
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p. 2170 - 2182
(2021/11/17)
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- Synthesis, crystal structure, DFT, molecular docking and antitumor activity of 4-(2-chlorobenzyl)-1-(5-fluoro-2-hydroxy-3-((4-methylpiperidin-1-yl)methyl)phenyl)-[1,2,4]triazolo[4,3-a]quinazolin-5(4H)-one
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In this study, the compound 4-(2-chlorobenzyl)-1-(5-fluoro-2-hydroxy-3-((4-methylpiperidin -1-yl)methyl)phenyl)-[1,2,4]triazolo[4,3-a]quinazolin-5(4H)-one (1) was synthesized for the first time, and its structure was characterized by 1H NMR, 13C NMR, MS and FT-IR spectra. Single crystals of compound 1 were grown in acetonitrile and the structure was confirmed by X-ray diffraction. The DFT-optimized structure was consistent with that determined by X-ray diffraction. Geometrical parameter, molecular electrostatic potential and frontier molecular orbital analyses were performed using the DFT/B3LYP/6-311G (2d, p) method. The vibrational assignment was based on the characteristic vibrational absorption band of compound 1. The theoretical and experimental 13C NMR chemical shifts exhibited good correlation. Molecular docking suggests favorable interactions between compound 1 and SHP2 protein. The SHP2 enzyme inhibition rate of compound 1 was 12.40% at 10?μM. The antitumor activity of 1 was better than that of the reference compound in human hepatoma cells SMMC7721 (IC50 = 757?μM) and human melanoma cells A375 (IC50 = 70.19?μM). Graphic abstract: [Figure not available: see fulltext.].
- Zhou, Zhi-xu,Wu, Qing-mei,Huang, Zhu-yan,Yu, De-hou,Lu, Hong-guang
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p. 3609 - 3627
(2021/06/09)
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- Synthesis, crystal structure and DFT study of a new compound (E)-3-(2-chlorobenzyl)-2-(propan-2-ylidenehydrazineylidene)-2,3-dihydroquinazolin-4(1H)-one
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(E)-3-(2-chlorobenzyl)-2-(propan-2-ylidenehydrazineylidene)-2,3-dihydroquinazolin-4(1H)-one is an organic intermediate. The structure of the target compound was confirmed using 1H NMR, 13C NMR, HRMS and FT-IR spectroscopy. The precise structure of (E)-3-(2-chlorobenzyl)-2-(propan-2-ylidenehydrazineylidene)-2,3-dihydroquinazolin-4(1H)-one was analyzed using single-crystal X-ray diffraction. Furthermore, the crystal structure of the title compound was optimized via DFT calculations, and the optimized structure was compared with the crystal structure after single-crystal X-ray diffraction. The results showed that the crystal structures determined via single crystal X-ray diffraction and DFT calculations were consistent with each other. Additionally, the molecular electrostatic potential and frontier molecular orbitals of the title compound were further studied using DFT calculations.
- Deng, Liyuan,Hu, Weiyin,Liao, Tianhui,Pan, Hongyan,Sun, Hong,Zhao, Chunshen,Zhou, Zhixu
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- CuBr-catalysed one-pot multicomponent synthesis of 3-substituted 2-thioxo-2,3-dihydroquinazolin-4(1H)-one derivatives
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A novel methodology is presented for the synthesis of 3-substituted 2-thioxo-2,3-dihydroquinazolin-4(1H)-one derivatives based on an efficient tandem multicomponent reaction using copper bromide as catalyst. This methodology is based on the multicomponent one-pot reaction of methyl 2-bromobenzoate, phenylisothiocyanate derivatives and sodium azide in the presence of copper bromide and l-proline under basic conditions. To show the generality of the method, various phenylisothiocyanates bearing electron-donating or electron-withdrawing functionalities were used and the desired products were obtained in high isolated yields.
- Sayahi, Mohammad Hosein,Saghanezhad, Seyyed Jafar,Bahadorikhalili, Saeed,Mahdavi, Mohammad
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- A green and efficient synthesis of 2-thioxoquinazolinone derivatives in water using potassium thiocyanate
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Green chemistry is one of the most important routes for the synthesis of heterocyclic compounds. In this regard, the synthesis of 2-thioxoquinazolinone derivatives was achieved by condensation of versatile materials including isatoic anhydride, amine and potassium thiocyanate in the green medium of water. This convenient and ef?cient method affords the desired products with good to excellent yields.
- Rezanejade Bardajee, Ghasem,Ghaedi, Aseyeh,Hekmat, Shohreh,Abarashi, Ghazale,Mahdavi, Mohammad,Akbarzadeh, Tahmineh
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p. 519 - 529
(2017/09/27)
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- Convenient and sequential one-pot route for synthesis of 2-thioxoquinazolinone and quinazolinobenzothiazinedione derivatives
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A new and efficient synthetic process has been developed for preparation of 2-thioxoquinazolinone and quinazolinobenzothiazinedione derivatives. The related products were synthesized through reaction of isatoic anhydride, amines/anthranilic acids, and carbon disulfide (CS2) in the presence of potassium hydroxide in ethanol at reflux. Graphical abstract: [Figure not available: see fulltext.]
- Asadi, Mehdi,Masoomi, Shiva,Ebrahimi, Seyed Mostafa,Mahdavi, Mohammad,Saeedi, Mina,Shafiee, Abbas,Foroumadi, Alireza
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p. 497 - 504
(2014/03/21)
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