四氢吡啶并[4,3-d]二氢嘧啶酮衍生物的合成及其初步抗癌活性测定.pdfVIP

DOI: 10.6023/cjoc201206006 研究简报 有机化学 Chinese Journal of Organic Chemistry NOTE 四氢吡啶并[4,3-d]二氢嘧啶酮衍生物的合成及其初步抗癌活性测定 王 晶 丁 丽 肖 笛 薛思佳* (a 上海师范大学生命与环境科学学院化学系 上海 200234) 摘要 为寻找新型抗癌药物的先导化合物, 设计合成了16种未见文献报道的四氢吡啶并[4,3-d]二氢嘧啶酮衍生物2a～ 2p, 结构经1H NMR, IR, MS, 元素分析确证. 初步的生物活性测试结果表明, 在100 μg/mL 浓度下, 目标化合物对白血 病K562 细胞的增殖表现出显著的抑制活性, 对卵巢癌HO-8910 和肝癌 SMMC-7721 细胞系的增殖也表现出一定的抑 制活性. 关键词 四氢吡啶并[4,3-d]二氢嘧啶酮; 衍生物; 合成; 白血病K562; 抗癌活性 Synthesis and Preliminary Anticancer Activity Evaluation of Tetrahydropyrido[4,3-d]dihydropyrimidine-2-one Derivatives Wang, Jing Ding, Li Xiao, Di Xue, Sijia* (a College of Life and Environment Sciences, Shanghai Normal University, Shanghai 200234) Abstract In search of more effective anticancer agents, sixteen novel tetrahydropyrido[4,3-d]dihydropyrimidine-2-one de- rivatives 2a ～2p were synthesized by reacting N-(4-substituted benzyl)-3,5-bisbenzylidene-4-piperidone with urea in EtONa/EtOH under reflux condition. The structures were confirmed by 1H NMR, IR, MS and elemental analysis. The pre- liminary bioassay indicated that some title compounds exhibited good antiproliferative activities against K562 cells, certain antiproliferative activities against ovarian cancer HO-8910 cells and liver cancer SMMC-7721 cells. Keywords tetrahydropyrido[4,3-d]dihydropyrimidine-2-one; derivative; synthesis; leukemic K562 cells; anticancer activi- ties 癌症是当今世界上死亡率最高的疾病之一, 它对人 制多种癌细胞的生物活性, 在新药创制领域具有重要的 类的健康造成了极严重的危害. 据世界卫生组织(WHO) 研究价值. 前期[5]研究表明, N-取代苄基-3,5-二苄亚甲 统计资料表明, 每年全世界癌症发病约1000万人, 死