1192150-15-4Relevant articles and documents
Efficient Synthesis and Biological Evaluation of 6-Trifluoroethoxy Functionalized Pteridine Derivatives as EGFR Inhibitors
Chen, Zhendong,Li, Zhulai,Lin, Jin,Lin, Xiongqiang,Lu, Tian,Wang, Jian,Xu, Xiuzhi,Zha, Daijun,Zhang, Zemin
, p. 353 - 363 (2022/03/09)
Background: Pteridine-based scaffolds have been widely prevalent in pharmaceuticals, such as kinase inhibitors targeting EGFR, FLT3 and PI3K/mTOR which are attractive targets for the anticancer therapy. Objective: This work aimed at designing and synthesizing 6-2,2,2-trifluoroethoxy functionalized pteridine-based derivatives for investigation of their anti-cancer activities as EGFR inhibitor. Methods: Pteridine-based derivatives were synthesized in 6 steps involving amination, bromination, cyclization, alkoxylation, chlorination and coupling reactions. Cellular anti-proliferative activities and inhibition activities on EGFR signaling of these pteridine derivatives in vitro were determined by the MTT assay and western blot analysis, respectively. Molecular docking simulation studies were carried out by the crystallographic structure of the erlotinib/EGFR kinase domain [Protein Data Bank (PDB) code: 1M17]. Results: The compound 7m, with IC50 values of 27.40 μM on A549 cell line, exhibited comparable anti-proliferative activity relative to the positive control. Besides, western blots showed its obvious down-regulation of p-EGFR and p-ERK expression at 0.8 μM. The molecular docking model displayed a hydrogen bond between Met-769 amide nitrogen and N-1 in pteridine motif of 7m which lied at the ATP binding site of EGFR kinase domain. Conclusion: The inhibition of 7m on cellular growth was comparable to that of the positive control. The inhibitory activities of 7m on EGFR phosphorylation and ERK phosphorylation in A549 cell line were relatively superior to that of the positive control. Both results suggested that the antiproliferative activity of 7m against A549 cell line was caused by inhibition of EGFR signaling pathway, providing a new perspective for the modification of pteridine-based derivatives as EGFR inhibitor.
Method for photocatalytic synthesis of quinazolinone compound in aqueous phase (by machine translation)
-
Paragraph 0030; 0031; 0032; 0033; 0060; 0061, (2020/11/22)
The method comprises the following steps: taking the compound of the formula (I) and the compound of the formula (II) as a solvent, adding a photocatalyst and a phase transfer catalyst to obtain the quinazolinone compound (III) under the condition of alkali and visible light. Compared with the prior art, the method not only can be applied to a large amount of functional groups, has high yield, few byproducts, and is simple and safe to operate, low in cost and environment-friendly. Wherein R is hydrogen or R1 Is H, C1 - C4 alkoxy, halogen or nitro; R2 Is H, substituted or unsubstituted phenyl, 2 - pyridyl or 2 - thienyl; the substituted phenyl is phenyl substituted by amino, nitro, C1 - C4 alkyl or C1 - C4 alkoxy. (by machine translation)
Efficient and selective microwave-assisted copper-catalyzed synthesis of quinazolinone derivatives in aqueous
Ke, Fang,Liu, Caiqin,Zhang, Peng,Xu, Jianhua,Chen, Xiaole
supporting information, p. 3089 - 3098 (2018/12/04)
Microwave-assisted copper-catalyzed cascade reactions between 2-halobenzoic acids and amidines to synthesize quinazolinone derivatives in water are reported. A variety of target products were obtained in good to excellent yields up to 94%. Its application was performed by the synthesis of 4-(1H-benzo[d]imidazol-2-ylthio)-6-methoxypteridine, which displayed significant anti-proliferation effect.
