In this study, a series of pyrrolo [2,3-d]pyrimidine derivatives containing 1,8-naphthyridine-4-one fragment were synthesized and their biological activity were tested. Most of the target compounds displayed moderate to excellent activity against one or more cancer cell lines and low activity against human normal cell LO2 in vitro. The most promising compound 51, of which the IC₅₀ values were 0.66 μM, 0.38 μM and 0.44 μM against cell lines A549, Hela and MCF-7, shown more remarkable activity and better apoptosis effect than the positive control Cabozantinib. The structure-activity relationships (SARs) indicated that double-EWGs (such as R₃ = 2-Cl-4-CF₃) on the terminal phenyl rings was a key factor in improving the biological activity. In addition, the further research on compound 51 mainly included c-Met kinase activity and selectivity, concentration dependence, and molecular docking.

在这项研究中，合成了一系列含有1,8-萘啶-4-酮片段的吡咯并[2,3- d ]嘧啶衍生物，并对其生物学活性进行了测试。多数目标化合物在体外对一种或多种癌细胞系表现出中度至优异的活性，而对人正常细胞LO2的活性低。最有前途的化合物51对细胞系A549，Hela和MCF-7的IC ₅₀值为0.66μM，0.38μM和0.44μM，与阳性对照Cabozantinib相比，显示出更出色的活性和更好的凋亡作用。构效关系（SAR）表示双EWG（例如R ₃  = 2-Cl-4-CF ₃末端苯环上的）是提高生物活性的关键因素。此外，对化合物51的进一步研究主要包括c-Met激酶的活性和选择性，浓度依赖性和分子对接。