A novel series of 4-(4-methoxynaphthalen-1-yl)-5-arylpyrimidin-2-amines were designed, synthesized, and evaluated for their anticancer activities. Most of the synthesized compounds exhibited moderate to high antiproliferative activity in comparison to the standard drug cisplatin. Among them, 5i bearing ethoxy at the 4-position of the phenyl was found to be the most active on MCF-7 and HepG2 cancer cell lines, with IC₅₀ values of 3.77 ± 0.36 and 3.83 ± 0.26 µM, respectively. Further mechanism study shown that 5i potently inhibited tubulin polymerization, induced cell cycle arrest at G2/M phase and cell apoptosis in MCF-7 cell line. Furthermore, molecular modeling study suggested that 5i probably binds to the colchicine site of tubulin.

设计，合成并评估了一系列新颖的4-（4-甲氧基萘-1-基）-5-芳基嘧啶-2-胺类化合物的抗癌活性。与标准药物顺铂相比，大多数合成的化合物均表现出中等至高的抗增殖活性。其中，发现在苯基的4位带有乙氧基的5i在MCF-7和HepG2癌细胞系中活性最高，IC ₅₀值分别为3.77±0.36和3.83±0.26 µM。进一步的机理研究表明，5i有效抑制微管蛋白聚合，诱导细胞周期停滞在G2 / M期以及MCF-7细胞株的细胞凋亡。此外，分子建模研究表明5i 可能与微管蛋白的秋水仙碱位点结合。