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

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*

(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

(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

Cite this article

TIAN Chao, LI Chao, ZHANG Zhi-Li, WANG Xiao-Wei, LIU Jun-Yi. Synthesis and Bioactivity of N⁵-Substituted 4-Amino-N⁸,N¹⁰-deazatetrahydrofolate Analogues[J]. Chin. J. Org. Chem., 2011, 31(11): 1820-1827.

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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

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

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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