A series of 4-(pyridin-4-yloxy)benzamide derivatives bearing a 5-methylpyridazin-3(2H)-one fragment were designed, synthesized, and evaluated for their biological activity. Most compounds showed effective inhibitory activity against cancer cell lines of A549, HeLa and MCF-7. Among them, the most promising compound 40 showed excellent activity against A549, HeLa and MCF-7 cell lines with IC₅₀ values of 1.03, 1.15 and 2.59 μM, respectively, which was 2.60-6.95 times more active than that of Golvatinib. The structure-activity relationships (SARs) showed that the introduction of 5-methylpyridazin-3(2H)-one to “5-atom linker” and the modification of the amide with morpholine group were beneficial for enhancing the inhibitory activity of compounds. In addition, the further research on compound 40 mainly include c-Met kinase activity, concentration dependence, apoptosis (acridine orange staining), and molecular docking.

设计，合成，评估一系列带有5-甲基吡啶并嗪-3（2 H）一个片段的4-（吡啶-4-基氧基）苯甲酰胺衍生物。大多数化合物显示出对A549，HeLa和MCF-7癌细胞系的有效抑制活性。其中，最有前途的化合物40对A549，HeLa和MCF-7细胞系表现出优异的活性，其IC ₅₀值分别为1.03、1.15和2.59μM，比Golvatinib的活性高2.60-6.95倍。构效关系（SARs）表明5-甲基哒嗪-3（2 H一个至“ 5-原子的连接基”和用吗啉基团修饰酰胺有助于增强化合物的抑制活性。此外，对化合物40的进一步研究主要包括c-Met激酶活性，浓度依赖性，细胞凋亡（ac啶橙染色）和分子对接。