Design, synthesis and biological evaluation of a series of dianilinopyrimidines as EGFR inhibitors

Journal of Enzyme Inhibition and Medicinal Chemistry

卷:37

Qin Wang¹  Li Liu¹  Longjia Yan¹  Yi Le¹ 

[1] School of Pharmaceutical Sciences, Guizhou University, Guiyang, China;

关键词: Design;    synthesis;    EGFR;    inhibitor;    antitumor;   

DOI  :  10.1080/14756366.2022.2046567

来源: DOAJ

【 摘 要 】

This paper described our efforts to develop dianilinopyrimidines as novel EGFR inhibitors. All the target compounds were tested for inhibitory effects against wild type EGFR (EGFRwt) and three tumour cells, including A549, PC-3, and HepG2. Some of the compounds performed well in antitumor activities. Especially, compound 4c 2-((2-((4-(3-fluorobenzamido)phenyl)amino)-5-(trifluoromethyl) pyrimidin-4-yl)amino)-N-methylthiophene-3-carboxamide showed higher anti-tumour activities than Gefitinib. The IC50 values of compound 4c against A549, PC-3, and HepG2. reached 0.56 μM, 2.46 μM, and 2.21 μM, respectively. In addition, further studies indicated that compound 4c could induce apoptosis against A549 cells and arrest A549 cells in the G2/M phase. Molecular docking studies showed that compound 4c could closely interact with EGFR. Generally, compound 4c was the potential for developing into an anti-tumour drug.

【 授权许可】

Unknown