Abstract A series of novel pyridazinone derivatives containing the 1,3,4-thiadiazole moiety were synthesized and characterized by 1H NMR, 13C NMR, spectroscopies HRMS and IR. Among them, the structure of compound 5c (2-(Tert-butyl)−4-chloro-5-((5-((2-ethylphenyl)amino)−1,3,4-thiadiazol-2-yl)thio)pyridazin-3(2H)-One) was unambiguously confirmed via single crystal X-ray diffraction analysis. The inhibitory activity of all the target compounds against MGC-803 and Bcap-37 was determined by MTT assay, with doxorubicin (the inhibition rates were 95.5 ± 0.4% and 95.7 ± 1.0% respectively) as a control. The preliminary results showed that the inhibitory activity of compound 5n (2-(Tert-butyl)−4-chloro-5-((5-((3-fluorophenyl)amino)−1,3,4-thiadiazol-2-yl)thio)pyridazin-3(2H)-One) was superior to the others. The inhibition rates of MGC-803 and Bcap-37 cells were 86.3 ± 2.2% and 92.3 ± 0.6% at a concentration of 10 μmol/L, respectively. The preliminary structure-activity relationship showed that when the 2-position of the benzene ring was substituted by a methyl group, such as compound 5j (2-(Tert-butyl)−4-chloro-5-((5-((2,3-dimethylphenyl)amino)−1,3,4-thiadiazol-2-yl)thio)pyridazin-3(2H)-One), it exhibited good anticancer activity on MGC-803 cells. Besides, introducing fluorine, chlorine, or trifluoromethyl group onto the benzene ring, such as compound 5 m (2-(Tert-butyl)−4-chloro-5-((5-((4-(trifluoromethoxy)phenyl)amino)−1,3,4-thiadiazol-2-yl)thio)pyridazin-3(2H)-One), displayed good anticancer activity on MGC-803 and Bcap-37 cells. Graphical Abstract

中文翻译：

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含有1,3,4-噻二唑部分的新型哒嗪酮衍生物的合成及抗肿瘤活性

摘要 合成了一系列含有1,3,4-噻二唑部分的新型哒嗪酮衍生物，并通过1H NMR、13C NMR、HRMS和IR光谱表征。其中，化合物5c的结构(2-(叔丁基)-4-氯-5-((5-((2-乙基苯基)氨基)-1,3,4-噻二唑-2-基)硫基)通过单晶 X 射线衍射分析明确证实了哒嗪-3(2H)-One)。通过MTT法测定所有目标化合物对MGC-803和Bcap-37的抑制活性，以阿霉素（抑制率分别为95.5±0.4%和95.7±1.0%）为对照。初步结果表明化合物5n(2-(叔丁基)-4-氯-5-((5-((3-氟苯基)氨基)-1,3,4-噻二唑-2-基) )thio)pyridazin-3(2H)-One) 优于其他。MGC-803和Bcap-37细胞在10 μmol/L浓度下的抑制率分别为86.3±2.2%和92.3±0.6%。初步的构效关系表明，当苯环的2-位被甲基取代时，如化合物5j(2-(叔丁基)-4-氯-5-((5-((2 ,3-二甲基苯基)氨基)-1,3,4-噻二唑-2-基)硫代)哒嗪-3(2H)-One)，对MGC-803细胞表现出良好的抗癌活性。此外，在苯环上引入氟、氯或三氟甲基，如化合物5m(2-(叔丁基)-4-氯-5-((5-((4-(三氟甲氧基)苯基)氨基)) -1,3,4-噻二唑-2-基)硫代)哒嗪-3(2H)-One)，对MGC-803和Bcap-37细胞显示出良好的抗癌活性。图形概要 初步的构效关系表明，当苯环的2-位被甲基取代时，如化合物5j(2-(叔丁基)-4-氯-5-((5-((2 ,3-二甲基苯基)氨基)-1,3,4-噻二唑-2-基)硫代)哒嗪-3(2H)-One)，对MGC-803细胞表现出良好的抗癌活性。此外，在苯环上引入氟、氯或三氟甲基，如化合物5m(2-(叔丁基)-4-氯-5-((5-((4-(三氟甲氧基)苯基)氨基)) -1,3,4-噻二唑-2-基)硫代)哒嗪-3(2H)-One)，对MGC-803和Bcap-37细胞显示出良好的抗癌活性。图形概要 初步的构效关系表明，当苯环的2-位被甲基取代时，如化合物5j(2-(叔丁基)-4-氯-5-((5-((2 ,3-二甲基苯基)氨基)-1,3,4-噻二唑-2-基)硫代)哒嗪-3(2H)-One)，对MGC-803细胞表现出良好的抗癌活性。此外，在苯环上引入氟、氯或三氟甲基，如化合物5m(2-(叔丁基)-4-氯-5-((5-((4-(三氟甲氧基)苯基)氨基)) -1,3,4-噻二唑-2-基)硫代)哒嗪-3(2H)-One)，对MGC-803和Bcap-37细胞显示出良好的抗癌活性。图形概要 4-噻二唑-2-基)硫)哒嗪-3(2H)-One)，对MGC-803细胞表现出良好的抗癌活性。此外，在苯环上引入氟、氯或三氟甲基，如化合物5m(2-(叔丁基)-4-氯-5-((5-((4-(三氟甲氧基)苯基)氨基)) -1,3,4-噻二唑-2-基)硫代)哒嗪-3(2H)-One)，对MGC-803和Bcap-37细胞显示出良好的抗癌活性。图形概要 4-噻二唑-2-基)硫)哒嗪-3(2H)-One)，对MGC-803细胞表现出良好的抗癌活性。此外，在苯环上引入氟、氯或三氟甲基，如化合物5m(2-(叔丁基)-4-氯-5-((5-((4-(三氟甲氧基)苯基)氨基)) -1,3,4-噻二唑-2-基)硫代)哒嗪-3(2H)-One)，对MGC-803和Bcap-37细胞显示出良好的抗癌活性。图形概要