| Study on Inhibitors of Methionine Synthase Ⅷ: Synthesis of 2,5-Diamino-4-oxo-6- (3-butenyl) pyrimidine |
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| 引用本文： | ZHANG Zhi-Li,WANG Hong-Tao,WANG Xiao-Wei,MA Xiao-Yan,LIU Jun-Yi,R.J. Griff,B.T. Golding.Study on Inhibitors of Methionine Synthase Ⅷ: Synthesis of 2,5-Diamino-4-oxo-6- (3-butenyl) pyrimidine[J].有机化学,2003,23(Z1):10-10. |
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| 作者姓名： | ZHANG Zhi-Li WANG Hong-Tao WANG Xiao-Wei MA Xiao-Yan LIU Jun-Yi R.J. Griff B.T. Golding |
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| 作者单位： | ZHANG Zhi-Li（Department of Chemical Biology, School of Pharmaceutical Sciences, Peking University, Beiiing 100083）
WANG Hong-Tao（Department of Chemical Biology, School of Pharmaceutical Sciences, Peking University, Beiiing 100083）
WANG Xiao-Wei（Department of Chemical Biology, School of Pharmaceutical Sciences, Peking University, Beiiing 100083）
MA Xiao-Yan（Department of Chemical Biology, School of Pharmaceutical Sciences, Peking University, Beiiing 100083）
LIU Jun-Yi（Department of Chemical Biology, School of Pharmaceutical Sciences, Peking University, Beiiing 100083）
R.J. Griff（Department of Chemistry, University of Newcastle, Newcastle upon Tyne, England）
B.T. Golding（Department of Chemistry, University of Newcastle, Newcastle upon Tyne, England） |
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| 基金项目： | Project supported by the National Natural Science Foundation of China (20172007). |
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| 摘 要： | Cobalamin-dependent methionine synthase plays a crucial role in folate metabolism and such would appear to be an excellent target for rational antifolate drug design. However, to date, no anticancer agents directed at this enzyme are available, but the enzyme is efficiently and specifically inhibited by N2O and this has proven invaluable for evaluating the biochemical consequence of enzyme inhibition and for mechanistic studies. 1,2] 2,5-Diamino-4-oxo-6-(3-butenyl) pyrimidine, a key intermediate in synthetic inhibitors of methionine synthase, was first synthesized using γbutenyl-β-ketoester and guanidine carbonate (Scheme 1). 3]
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Study on Inhibitors of Methionine Synthase Ⅷ: Synthesis of 2,5-Diamino-4-oxo-6- (3-butenyl) pyrimidine |
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| ZHANG Zhi-Li,WANG Hong-Tao,WANG Xiao-Wei,MA Xiao-Yan,LIU Jun-yi,R.J. Griff,B.T. Golding.Study on Inhibitors of Methionine Synthase Ⅷ: Synthesis of 2,5-Diamino-4-oxo-6- (3-butenyl) pyrimidine[J].Chinese Journal of Organic Chemistry,2003,23(Z1):10-10. |
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| Authors: | ZHANG Zhi-Li WANG Hong-Tao WANG Xiao-Wei MA Xiao-Yan LIU Jun-yi RJ Griff BT Golding |
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| Abstract: | Cobalamin-dependent methionine synthase plays a crucial role in folate metabolism and such would appear to be an excellent target for rational antifolate drug design. However, to date, no anticancer agents directed at this enzyme are available, but the enzyme is efficiently and specifically inhibited by N2O and this has proven invaluable for evaluating the biochemical consequence of enzyme inhibition and for mechanistic studies. 1,2] 2,5-Diamino-4-oxo-6-(3-butenyl) pyrimidine, a key intermediate in synthetic inhibitors of methionine synthase, was first synthesized using γbutenyl-β-ketoester and guanidine carbonate (Scheme 1). 3] |
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