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新型2-取代苄基硫代嘧啶衍生物的合成及其细胞毒性

Synthesis and Cytotoxicity of Novel 2-Substituted Benzyl Sulfo-pyrimidine Derivatives
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摘要 以乙酰乙酸乙酯和硫脲为起始原料,经环合、取代、氯代和亲核取代反应合成了16个新型的2-取代苄基硫代嘧啶衍生物(7a^7p),其结构经1H NMR,13C NMR和HR-MS表征。细胞毒性测试结果表明:6-甲基-4-对氯苯胺-2-苄基硫代嘧啶(7b)和6-甲基-4-对溴苯胺-2-苄基硫代嘧啶(7c)对MGC-803(人胃癌细胞)具有较好的抑制活性,其IC50分别为3.126μg·m L-1和2.197μg·m L-1,优于5-氟尿嘧啶(IC503.208μg·m L-1)。 Sixteen novel 2-substituted benzyl sulfo-pyrimidine derivatives（ 7a - 7p） were synthesized by a four-step reactions of cyclization,substitution,chlorination and nucleophilic substitution,using ethyl acetoacetate and thiourea as raw materials. The structures were characterized by1 H NMR,13 C NMR and HR-MS. Cytotoxicity in vitro tests indicated that 6-methyl-4-parachloroaniline-2-benzyl sulfo-pyrimidine（ 7b） and 6-methyl-4-parabromoaniline-2-benzyl sulfo-pyrimidine（ 7c） exhibited the best activities against MGC-803（ human gastric cancer cell line） with 3. 126 μg·m L- 1and 2. 197μg·m L^- 1of IC50,respectively,which were better than 5-FU（ IC503. 208 μg·m L^- 1）
作者 顾一飞 王超杰 曹钦坡 张孝松 陈鹏举 蒋腾飞 邵坤鹏 李博 可钰 张秋荣 刘宏民
机构地区 郑州大学药学院新药创制与药物安全新评价河南省协同创新中心
出处 《合成化学》 CAS CSCD 2015年第6期461-465,475,共6页 Chinese Journal of Synthetic Chemistry
基金 国家自然科学基金资助项目(81172937)
关键词 嘧啶 硫脲嘧啶衍生物 合成 细胞毒性 pyrimidine thiouracil derivative synthesis cytotoxicity
分类号 O626.41 [理学—有机化学] O625.52 [理学—有机化学]
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参考文献19

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