Chin. J. Org. Chem. ›› 2011, Vol. 31 ›› Issue (11): 1820-1827. Previous Articles     Next Articles

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4-氨基-N8,N10-二碳杂-N5-取代四氢叶酸类似物的合成及生物活性研究

田超,李超,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:2011-04-17 修回日期:2011-05-20 发布日期:2011-06-10
  • 通讯作者: 刘俊义 E-mail:jyliu@bjmu.edu.cn

Synthesis and Bioactivity of N5-Substituted 4-Amino-N8,N10-deazatetrahydrofolate Analogues

TIAN Chao, LI Chao, ZHANG Zhi-Li, WANG Xiao-Wei, LIU Jun-Yi   

  1. (Department of Chemical Biology, School of Pharmaceutical Sciences, Peking University, Beijing 100191)
  • Received:2011-04-17 Revised:2011-05-20 Published:2011-06-10

The backbone of folate analogue was constructed via Wittig reaction between 2,4-diamino-6- hydroxymethylpyrido[3,2-d]pyrimidine and di-ethyl-N-[4-(formyl)benzoyl]-L-glutamate. Four new 4-amino- N8,N10-deazatetrahydrofolate analogues were obtained by hy-drogenating of pyridine ring and linking different substituent on N5 position. The compounds were characterized by 1H NMR, 13C NMR and MS techniques. The inhibitory activities against human thymidylate synthetase were determined. The results showed that the bioactivities of the compounds were related with different substituents on N5 position. The inhibitory rates of two compounds against leukemia cell line HL-60 were above 60% at 0.1 μmol•L-1.

Key words: 4-amino-N8,N10-deazatetrahydrofolate analogue, thymidylate synthetase, anticancer activity