Ding, Shi; Dong, Xiaoyong; Gao, Ziye; Zheng, Xiangshan; Ji, Jingchao; Zhang, Mingjuan; Liu, Fang; Wu, Shuang; Li, Min; Song, Wenshan; Shen, Jiwei; Duan, Wenwen; Liu, Ju; Chen, Ye published an article in 2022. The article was titled 《Design, synthesis and biological evaluation of novel N-(3-amino-4-methoxyphenyl)acrylamide derivatives as selective EGFRL858R/T790M kinase inhibitors》, and you may find the article in Bioorganic Chemistry.Reference of 2,4-Dichloropyrimidine The information in the text is summarized as follows:
On the basis of N-(3-amino-4-methoxyphenyl)acrylamide scaffold, a series of novel compounds containing 3-substitutional-1-methyl-1H-indole, 2-substitutional pyrrole or thiophene moieties were synthesized and their in vitro antiproliferation activities against A549 and H1975 cell lines were evaluated. The results indicated that most of the compounds showed moderate to excellent antitumor activities. Especially, compounds 9a (A549 IC50 = 1.96 μM, H1975 IC50 = 0.095 μM), 17i (A549 IC50 = 4.17 μM, H1975 IC50 = 0.052 μM), 17j (A549 IC50 = 1.67 μM, H1975 IC50 = 0.061 μM) exhibited comparable antitumor activities and selectivity ratios compared to the pos. control osimertinib (A549 IC50 = 2.91 μM, H1975 IC50 = 0.064 μM). In vitro inhibitory activities against EGFR kinases containing different mutations were also tested. Compound 17i showed remarkable inhibitory activity (with IC50 value of 1.7 nM) to EGFRL858R/T790M kinase and selectivity (22-folds compared to EGFRWT kinase). Furthermore, acridine orange/ethidium bromide (AO/EB) staining assay, cell apoptosis assay, cell cycle distribution assay and wound-healing assay of the compounds 9a and 17i were performed on H1975 cell line. The results showed dose-dependent activities of the induction of apoptosis, G0/G1-phase arrestation and inhibition of migration, which were similar to the pos. control osimertinib. Addnl., mol. docking analaysis was performed to seek the possible binding mode between the selected compounds (9a, 17i-17j) and EGFRL858R/T790M kinase. The results demonstrated that compound 17i is a promising candidate and worth further study. In the experimental materials used by the author, we found 2,4-Dichloropyrimidine(cas: 3934-20-1Reference of 2,4-Dichloropyrimidine)
2,4-Dichloropyrimidine(cas: 3934-20-1) is a member of organic chlorides. Almost all organochlorine compounds are synthesized. It is widely used as intermediates, solvents and pesticides of chemical synthetic products.Reference of 2,4-Dichloropyrimidine
Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia