Three series of novel 4-phenoxypyridine derivatives containing 4-methyl-6-oxo-1,6-dihydropyridazine- 3-carboxamide, 5-methyl-4-oxo-1,4-dihydropyridazine-3-carboxamide and 4-methyl-3,5-dioxo-2,3,4,5- tetrahydro-1,2,4-triazine-6-carboxamide moieties were synthesized and evaluated for their in vitro inhibitory activitives against c-Met kinase and cytotoxic activitives against A549, H460, HT-29 cancer cell lines. The results indicated that most of the compounds showed moderate to good antitumor activitives. The most promising compound 26a (with c-Met IC₅₀ value of 0.016 μM) showed remarkable cytotoxicity against A549, H460, and HT-29 cell lines with IC₅₀ values of 1.59 μM, 0.72 μM and 0.56 μM, respectively. Their preliminary structure-activity relationships (SARs) studies indicate that 4-methyl-3,5-dioxo-2,3,4,5-tetrahydro-1,2,4-triazine-6-carboxamide was more preferred as linker part, and electron-withdrawing groups on the terminal phenyl rings are beneficial for improving the antitumor activitives. Furthermore, the colony formation, acridine orange/ethidium bromide (AO/EB) staining, apoptosis, and wound-healing assay of 26a were performed on HT-29 and/or A549 cell lines.

包含4-甲基-6-氧代-1,6-二氢哒嗪-3-羧酰胺，5-甲基-4-氧代-1,4-二氢哒嗪-3-羧酰胺和4-甲基-3的三个系列的新型4-苯氧基吡啶衍生物合成了5-5-二氧代-2,3,4,5-四氢-1,2,4-三嗪-6-羧酰胺基团，并评估了其对c-Met激酶的体外抑制活性和对A549，H460， HT-29癌细胞系。结果表明，大多数化合物显示出中等至良好的抗肿瘤活性。最有前途的化合物26a（c-Met IC ₅₀值为0.016μM）对具有IC _50的A549，H460和HT-29细胞系表现出显着的细胞毒性分别为1.59μM，0.72μM和0.56μM。他们的初步结构-活性关系（SAR）研究表明，4-甲基-3,5-二氧杂-2,3,4,5-四氢-1,2,4-三嗪-6-羧酰胺更优选用作连接基，末端苯环上的吸电子基团对于改善抗肿瘤活性剂是有利的。此外，在HT-29和/或A549细胞系上进行了26a的集落形成，a啶橙/溴化乙锭（AO / EB）染色，凋亡和伤口愈合分析。