Identification of hydrazone moiety-bearing aminopyrimidines as potent antitumor agents with selective inhibition of gefitinib-resistant H1975 cancer cells

Based on our previous work, a series of hydrazone moiety-bearing aminopyrimidines were synthesized. The compounds were evaluated for inhibitory activities against EGFR T790M/L858R and antiproliferative activities against H1975 and A549 NSCLC cell lines harboring different forms of EGFR. Compounds 7f and 7k exhibited potent and selective activity in inhibition of gefitinib-resistant H1975 cancer cells (IC₅₀; 0.45, 0.2 μmol/L) while were much less active on A549 cancer cells (IC₅₀; 52.83, >100 μmol/L). Both compounds could be served as promising lead compounds for further investigation.