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

Abstract

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 (EGFR^wt) 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.

Keywords:

• Design
• synthesis
• EGFR
• inhibitor
• antitumor

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This work was financially supported by GZU (Guizhou University) Found for Newly Enrolled Talent ([2019]15), GZU (Guizhou University) Found for Cultivation ([2019]65), and the State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Medical University [Grant number FAMP202005K]; Guizhou Science and Technology Platform Talents [QKHRCPT [2019]5106].