Li, Yingxue; Chang, Yaoyao; Fu, Jianfang; Ding, Rongcai; Zhang, Lingyun; Liang, Tian; Liu, Yajing; Liu, Yue; Hu, Jinxing published their research in European Journal of Medicinal Chemistry in 2021. The article was titled 《Design, synthesis and biological evaluation of aminopyrimidine derivatives bearing a 4,5,6,7-tetrahydrothieno [3,2-c]pyridine as potent EGFR inhibitors》.Formula: C4H2Cl2N2 The article contains the following contents:
To resolve the problem of drug resistance caused by epidermal growth factor receptor (EGFR) mutations in non-small cell lung cancer, the principle of collocation was used to design and synthesize a series of aminopyrimidine derivatives with 4,5,6,7-tetrahydrothieno [3,2-c]pyridine side chains (according to the binding mode of AZD9291 to EGFRT790M) for use as EGFRL858R/T790M kinase inhibitors. The most promising compound N-(5-((5-chloro-4-(6,7-dihydrothieno [3,2-c]pyridin-5(4H)-yl)pyrimidin-2-yl) amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)propionamide, a non-covalently bound reversible inhibitor, showed excellent kinase inhibitory activity against EGFRL858R/T790M, with an IC50 value of 4.0 nM and more than 42-fold selectivity for EGFRWT (IC50 = 170.0 nM). Moreover, the above compound showed strong anti-proliferative activity against H1975 cells, with IC50 value of 0.086μΜ. Addnl., the effective inhibition of cell migration and the promotion of apoptosis by the above compound verified its mechanism of action, as a selective inhibitor of EGFRL858R/T790M. The experimental process involved the reaction of 2,4-Dichloropyrimidine(cas: 3934-20-1Formula: C4H2Cl2N2)
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.Formula: C4H2Cl2N2
Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia