Small molecule inhibitors of biphenyl structure as core backbone have shown a significant effect on PD-1/PD-L1 axis, and 2-amino-pyrimidine structure is a promising privileged scaffold in medicinal chemistry and drug discovery. We designed by combination principles and synthesized 27 novel compounds with N-((2-methyl-[1,1′-biphenyl]-3-yl)methyl)pyrimidin-2-amine as a basic skeletal structure, and their anti-cancer activity was evaluated. Among compounds, 15a-d and 16b displayed strong anti-cancer effects on 9 tested cancer cell lines, in particular, the 16b did the highest inhibitive activity, but against HepG2 cells, and possessed the lowest IC₅₀ value of 2.08 μΜ towards HT-29 cells.

以联苯结构为核心骨架的小分子抑制剂已对PD-1 / PD-L1轴显示出显著作用，而2-氨基-嘧啶结构是药物化学和药物开发中有希望的特权支架。我们根据结合原理设计并合成了以N -（（2-甲基-[1,1'-联苯] -3-基）甲基）嘧啶-2-胺为基本骨架结构的27种新化合物及其抗癌作用活动进行了评估。在化合物中，15a-d和16b对9种经过测试的癌细胞系表现出强大的抗癌作用，特别是16b的抑制活性最高，但对HepG2细胞的抑制作用最低，对HT-的IC ₅₀值为2.08μM。 29个单元格。