In order to find more effective antitumor drugs, a series of novel 2,4-substituted pyrimidine derivatives containing trifluoromethyl were designed, synthesized, and evaluated for antitumor activity aganist EC-109 (human esophageal cancer cell), MGC-803 (human gastric cancer cell), PC-3 (human prostate cancer cell) and HepG-2 (human liver cancer cell). The results showed that some compounds displayed moderate to potent antitumor activity against PC-3. Among them, 2-(((4-((1methyl-1H-tetrazol-5-yl)thio)-6-(trifluoromethyl)pyrimidin-2-yl)thio)methyl)benzo[d]thiazole (13w) possesses strong antitumor activity against PC-3 with IC 50 value of 1.76 µmol•L-1 , and the antitumor activity is significantly better than the positive control drug of 5-fluorouracil.

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With the aim of obtaining potential antitumor candidates with more efficiency and more economic value. 40 2,4,6-trisubstituted pyrimidine derivatives bearing chalcone moiety were synthesized via cyclization, chlorination, substitution with benzoylacetate and ethylacetoacetate as the starting materials. The structures of target products were confirmed by 1 H NMR, I3 C NMR and HRMS. 2,4,6-Trisubstituted pyrimidine derivatives bearing chalcone moiety were evaluated for anticancer activity on four human cancer cell lines including EC-109, MGC-803, HepG-2 and MDA-MB-231 by CCK-8 (cell counting Kit-8) assay. Among them, (E)-1-(4-((2-(((1H-benzo[d]imidazol-2-yl)methyl)thio)-6-methylpyrimidin-4-yl)amino)phenyl)-3-(3,4,5-trimethoxyphenyl)prop-2-en-1-one (13u) were more cytotoxic against MGC-803 and MDA-MB-231 cell lines, with IC 50 values of 0.99 and 1.77 μmol•L-1 , respectively.

a 郑州大学药学院 郑州 450001) (b 新药创制与药物安全性评价河南省协同创新中心 郑州 450001) (c 河南省药物质量评价重点实验室 郑州 450001) (d 教育部药物制备关键技术重点实验室 郑州 450001) 摘要 为了寻找新的具有靶向治疗作用的抗肿瘤药物, 设计并合成了一系列新型的含脲砌块的 4-氨基喹唑啉类衍生物, 并采用噻唑蓝(MTT)法测定目标化合物对 MCF-7(人乳腺癌细胞)、MGC-803(人胃癌细胞)、SW620(人结肠癌细胞)、 A549(人肺癌细胞)四种肿瘤细胞的抗肿瘤活性. 结果显示大部分化合物具有较好的抗肿瘤活性, 其中 2-((4-((3,4,5-三甲 氧基苯基)-氨基)喹唑啉-2-基)-硫代)-N-((3,4,5-三甲氧基苯基)氨基甲酰基)乙酰胺(10p)对 MGC-803、SW620 和 A549 三 种细胞显示出最好的抗肿瘤活性, IC 50 值分别为(7.02±0.46)、(6.00±0.78)和(7.04±1.11) µmol•L-1 , 其抗肿瘤活性和阳 性对照品吉非替尼相当. 分子对接结果显示, 化合物 10p 能与 EGFR 很好地结合, 有可能成为潜在的抗肿瘤药物.