| 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 |
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| 引用本文： | 田超,李超,张志丽,王孝伟,刘俊义.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[J].有机化学,2011,31(11). |
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| 作者姓名： | 田超 李超 张志丽 王孝伟 刘俊义 |
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| 作者单位： | 北京大学药学院化学生物学系 北京100191 |
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| 基金项目： | 国家自然科学基金，国家博士点基金 |
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| 摘 要： | 以2,4-二氨基-6-羟甲基吡啶并3,2-d]嘧啶为原料,与对甲酰基苯甲酰谷氨酸二乙酯发生Wittig反应构建叶酸类似物的骨架结构,还原吡啶环得到4-氨基-8,10-二碳杂四氢叶酸类似物,在N5位取代不同基团得到四个新的4-氨基-N8,N10-二碳杂四氢叶酸类化合物,经1H NMR,13C NMR和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胸苷酸合成酶的抑制作用与N5位取代基有关,2个化合物在0.1 μmol·L-1的浓度下对HL-60白血病细胞的抑制率达到60％以上.
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| 关 键 词： | 4-氨基-N8 N10-二碳杂四氢叶酸类似物 胸苷酸合成酶 抗癌活性 |
Synthesis and Bioactivity of N5-Substituted 4-Amino-N8,N10-deaza-tetrahydrofolate Analogues |
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| Tian, Chao,Li, Chao,Zhang, Zhili,Wang, Xiaowei,Liu, Junyi.Synthesis and Bioactivity of N5-Substituted 4-Amino-N8,N10-deaza-tetrahydrofolate Analogues[J].Chinese Journal of Organic Chemistry,2011,31(11). |
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| Authors: | Tian Chao Li Chao Zhang Zhili Wang Xiaowei Liu Junyi |
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| Institution: | Tian,Chao Li,Chao Zhang,Zhili Wang,Xiaowei Liu,Junyi (Department of Chemical Biology,School of Pharmaceutical Sciences,Peking University,Beijing 100191) |
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| Abstract: | The backbone of folate analogue was constructed via Wittig reaction between 2,4-diamino-6-hydroxymethylpyridopyrimidine and diethyl-N-4-(formyl)benzoyl]-L-glutamate.Four new 4-amino-N8,N10-deazatetrahydrofolate analogues were obtained by hydrogenating of pyridine ring and linking differ-ent substituent on N5 position.The compounds were characterized by 1H NMR,13C NMR and MS tech-niques.The inhibitory activities against human thymidylate synthetase were determined.The results showed that the bioactivities o... |
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| Keywords: | 4-amino-N8 N10-deazatetrahydrofolate analogue thymidylate synthetase anticancer activity |
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