Design, synthesis and antiproliferative activity of novel 5-nitropyrimidine-2,4-diamine derivatives bearing alkyl acetate moiety

Abstract In order to discover new anticancer drug leads, a series of novel alkylamino pyrimidine derivatives were designed and synthesized based on our previous work via a ring-opening strategy. Biological evaluation with four human cancer cell lines (MDA-MB-231, A549, HepG2, and MCF-7) showed that most of these compounds possessed moderate to potent antiproliferative activities. The most promising compound 7w displayed a three-fold improvement compared with commercial anticancer drug fluorouracil in inhibiting HepG2 cell proliferation with IC 50 value of 10.37 μM. Moreover, flow-activated cell sorting analysis suggested that compound 7w mainly arrested HepG2 cells in G 2 /M stage. Hence, it could serve as a promising lead for the design of novel anticancer small-molecule drugs.