The inhibition of the members of aurora kinase family using ATP-competitive small molecules is an effective method for anticancer therapeutics. Based on our previous work, we synthesized 12 new N-trisubstituted pyrimidine derivatives and evaluated their biological activities and stabilities. Among them, compound 11j showed the best inhibition against aurora A kinase (IC₅₀ = 7.1 nM), human leukemia cell line U937 (IC₅₀ = 12.2 nM) and the growth of U937 xenograft tumors in vivo. By the flow cytometry and immunofluorescence analysis of U937, we found that compound 11j can induced polyploidy formation including (4N, 8N and 16N) and induce defects in both chromosome alignment and spindle formation. Furthermore, compound 11j exhibited good chemical, physical, and thermal stabilities. All these results suggested that 11j is a promising lead compound for further development of anticancer drugs.

使用ATP竞争性小分子抑制极光激酶家族成员是一种有效的抗癌治疗方法。根据我们以前的工作，我们合成了12种新的N-三取代的嘧啶衍生物，并评估了它们的生物学活性和稳定性。其中，化合物11j对Aurora A激酶（IC ₅₀  = 7.1 nM），人白血病细胞系U937（IC ₅₀  = 12.2 nM）和U937异种移植瘤的体内生长表现出最好的抑制作用。通过U937的流式细胞仪和免疫荧光分析，我们发现化合物11j可以诱导包括（4N，8N和16N）在内的多倍体形成，并诱导染色体排列和纺锤体形成方面的缺陷。此外，化合物11j表现出良好的化学，物理和热稳定性。所有这些结果表明，11j是抗癌药物进一步开发的有前途的先导化合物。