32587-10-3Relevant 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.
Preparation method for pyrazine derivative
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Paragraph 0023; 0024, (2018/03/24)
The invention discloses a preparation method for a pyrazine derivative 3-amino-6-(3-chloro-5-methylphenyl)pyrazine-2-carboxamide. The method comprises the following steps: 3-aminopyrazine-2-carboxylic acid is used as a starting raw material, an esterification reaction is performed, an amidation reaction is performed, a bromination reaction is performed, a coupling reaction is performed, and therefore the objective product is obtained. The compound is an important pharmaceutical intermediate.
FUSED PYRAZINE COMPOUNDS AS THEIR SALTS, USEFUL FOR THE TREATMENT OF DEGENERATIVE AND INFLAMMATORY DISEASES
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Page/Page column 13, (2011/06/10)
Novel salts of a [1.2.4]triazolo[1,5-a]pyrazine compound according to Formula I: The salts may be prepared as pharmaceutical compositions, and may be used for the prevention and treatment of a variety of conditions in mammals including humans, including by way of non-limiting example, inflammation, and others.
