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有机化学
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有机化学 ›› 2010, Vol. 30 ›› Issue (11): 1721-1725. 上一篇    下一篇

研究论文

N8-去氮-N5-取代四氢叶酸类似物的设计合成及生物活性研究

闫汝锋，田超，郭莹，张志丽，王孝伟，刘俊义*   

  1. (北京大学药学院化学生物学系 北京100191)
  • 收稿日期:2010-03-06 修回日期:2010-06-10 发布日期:2010-06-24
  • 通讯作者: 闫汝锋 E-mail:yanrf031@163.com

Studies on Synthesis and Bioactivity of N8-Deaza-N5-tetrahydrofolate Analogues

YAN Ru-Feng, TIAN Chao, GUO Ying, ZHANG Zhi-Li, WANG Xiao-Wei, LIU Jun-Yi   

  1. (Department of Chemical Biology, School of Pharmaceutical Sciences, Peking University, Beijing 100191)
  • Received:2010-03-06 Revised:2010-06-10 Published:2010-06-24

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以2,4-二氨基-6-羟甲基吡啶并[3,2-d]嘧啶为原料, 在4-位氨基转换为羟基后与对氨基苯甲酰谷氨酸二乙酯连接生成叶酸类似物分子骨架, 采用Adams催化方法还原吡啶环, 在N5-位连接不同类型的取代基得到3个新的N8-去氮四氢叶酸类似物. 经1H NMR, MS对化合物的结构进行了表征. 初步生物活性结果表明, 此类化合物对人重组二氢叶酸还原酶的抑制活性与N5-位的取代基有关联.

关键词: N8-去氮-N5-取代叶酸类似物, 二氢叶酸还原酶, 抗癌

The backbone of folate analogue was obtained by linking di-ethyl-N-(p-aminobenzoyl)-L- glutamate and 2-amino-4-hydroxy-6-(hydroxymethyl)pyrido[3,2-d]pyrimidine. Three new 8-deazatetra- hydrofolate analogues were synthesized after reducing the pyrimidine and linking different substituents on N5 position. The compounds were characterized by 1H NMR and MS techniques. The inhibitory activities of the compounds against human dihydrofolate reductase were determined. The re-sults showed that the bioactivities of the compounds were related with different substituents on N5 position.

Key words: N8-deaza-N5-substitutedtetrahydrofolate analogue, dihydrofolate reductase, anticancer activity