Novel third-generation pyrimidines-based EGFR tyrosine kinase inhibitors targeting EGFR T790M mutation in advanced non-small cell lung cancer

•A series of pyrimidine derivatives containing thiophene fragment were designed and synthesized.•Compound 6a exhibited potent antiproliferative activity (2.2 nM) against H1975 cells.•Compound 6a strongly affected EGFR-mediated signaling pathways.•Compound 6a displayed acceptable pharmacokinetics (PK) parameters and exhibits promising antitumor efficacy.