56341-41-4Relevant articles and documents
Design, synthesis, and in vitro and in vivo anti-angiogenesis study of a novel vascular endothelial growth factor receptor-2 (VEGFR-2) inhibitor based on 1,2,3-triazole scaffold
Wang, De-pu,Liu, Kai-li,Li, Xin-yang,Lu, Guo-qing,Xue, Wen-han,Qian, Xin-hua,Mohamed O, Kamara,Meng, Fan-hao
, (2020/12/21)
In the past five years, our team had been committed to click chemistry research, exploring the biological activity of 1,2,3-triazole by synthesizing different target inhibitors. In this study, a series of novel indole-2-one derivatives based on 1,2,3-triazole scaffolds were synthesized for the first time, and their inhibitory activity on vascular endothelial growth factor receptor-2 (VEGFR-2) was tested. Most of the compounds had shown promising activity in the VEGFR-2 kinase assay and had low toxicity to human umbilical vein endothelial cells (HUVECs). The compound 13d (IC50 = 26.38 nM) had better kinase activity inhibition ability than sunitinib (IC50 = 83.20 nM) and was less toxic to HUVECs. Moreover, it had an excellent inhibitory effect on HT-29 and MKN-45 cells. On the one hand, by tube formation assay, transwell, and Western blot analysis, compound 13d could inhibit VEGFR-2 protein phosphorylate on HUVECs, thereby inhibiting HUVECs migration and tube formation. In vivo study, the zebrafish model with VEGFR-2 labeling also verified that compound 13d had more anti-angiogenesis ability than sunitinib. On the other hand, molecular docking and molecular dynamics (MD) simulation results showed that compound 13d could stably bind to the active site of VEGFR-2. Based on the above findings, compound 13d could be considered an effective anti-angiogenesis drug and has more development value than sunitinib.
A novel methodology for the efficient synthesis of 3-monohalooxindoles by acidolysis of 3-phosphate-substituted oxindoles with haloid acids
Huang, Tiao,Kong, Dulin,Li, Yue,Liu, Li,Wu, Mingshu
, p. 2321 - 2328 (2021/09/22)
A novel method for the synthesis of 3-monohalooxindoles by acidolysis of isatin-derived 3-phosphate-substituted oxindoles with haloid acids was developed. This synthetic strategy involved the preparation of 3-phosphate-substituted oxindole intermediates and SN1 reactions with haloid acids. This new procedure features mild reaction conditions, simple operation, good yield, readily available and inexpensive starting materials, and gram-scalability.
Preparation method for 5-fluoroindole-2-ketone
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, (2018/12/13)
The invention discloses a preparation method for 5-fluoroindole-2-ketone. The preparation method comprises the following steps: taking 2,4-difluoronitrobenzene as a raw material, enabling the 2,4-difluoronitrobenzene to perform condensation reaction with dimethyl malonate in an aprotic polar solvent under an inorganic alkaline condition, and performing post-treatment to obtain 4-fluoro-2-(dimehtylmalonate) nitrobenzene; in the presence of the aprotic polar solvent and lithium chloride, enabling the 4-fluoro-2-(dimehtyl malonate) nitrobenzene to generate 5-fluoro-2- nitrobenzene methyl acetate; mixing the 5-fluoro-2- nitrobenzene methyl acetate, a catalyst and alcohol solvents to perform hydrogenation cyclization reaction to obtain a 5-fluoroindole-ketone crude product; taking water as thesolvent by the crude product, filtering active carbon while hot, and re-crystallizing to obtain high-purity 5-fluoro-indole-2-ketone. The method adopts easily available raw materials, is simple in process; and a Raney nickel catalyst and a recrystallization aqueous solution can be used for many times, the raw material cost is relatively low, industrialization is easily realized, and the application prospect is relatively great.