ethyl (2S)-2-{[{[(2R,3R,4R,5R)-5-(4-amino-2-oxopyrimidin-1(2H)-yl)-3,4-dihydroxy-4-methyltetrahydrofuran-2-yl]methoxy}(4-chlorophenoxy)phosphoryl]amino}propanoate | 1035638-04-0

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: ethyl (2S)-2-{[{[(2R,3R,4R,5R)-5-(4-amino-2-oxopyrimidin-1(2H)-yl)-3,4-dihydroxy-4-methyltetrahydrofuran-2-yl]methoxy}(4-chlorophenoxy)phosphoryl]amino}propanoate
• 英文别名: 5'-O-[(4-chlorophenoxy)[[(1S)-2-ethoxy-1-methyl-2-oxoethyl]amino]phosphinyl]-2'-C-methylcytidine；ethyl (2S)-2-[[[(2R,3R,4R,5R)-5-(4-amino-2-oxopyrimidin-1-yl)-3,4-dihydroxy-4-methyloxolan-2-yl]methoxy-(4-chlorophenoxy)phosphoryl]amino]propanoate
• CAS: 1035638-04-0
• 化学式: C₂₁H₂₈ClN₄O₉P
• 分子量: 546.901
• InChiKey: UJVJXIDGFAFXMM-ZYQXLMQESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.2
• 重原子数：
  36
• 可旋转键数：
  11
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  182
• 氢给体数：
  4
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  ethyl (2S)-2-{[{[(2R,3R,4R,5R)-5-(4-amino-2-oxopyrimidin-1(2H)-yl)-3,4-dihydroxy-4-methyltetrahydrofuran-2-yl]methoxy}(4-chlorophenoxy)phosphoryl]amino}propanoate 在 potassium tert-butylate 作用下， 以 二甲基亚砜 为溶剂， 反应 0.5h， 以67%的产率得到ethyl N-[(2S,4aR,6R,7R,7aR)-6-(4-amino-2-oxopyrimidin-1(2H)-yl)-7-hydroxy-7-methyl-2-oxotetrahydro-4H-furo[3,2-d][1,3,2]dioxaphosphinin-2-yl]-L-alaninate
  参考文献：
  名称：

  Cyclic phosphoramidates as prodrugs of 2′-C-methylcytidine

  摘要：

  The currently approved treatment for hepatitis C virus infections is a combination of Ribavirin and pegylated Interferon. It leads to a sustained virologic response in approximately only half of the patients treated. For this reason there is an urgent need of new therapeutic agents. 2'-C-Methylcytidine is the first nucleoside inhibitor of the HCV NS5B polymerase that was efficacious in reducing the viral load in patients infected with HCV. The application of a monophosphate prodrug approach based on unprecedented cyclic phosphoramidates is reported. Our SAR studies led to compounds that are efficiently converted to the active triphosphate in human hepatocytes. (C) 2009 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2009.04.043
• 作为产物：
  描述：

  ethyl (2S)-2-{[{[(2R,3R,4R,5R)-5-(4-amino-2-oxopyrimidin-1(2H)-yl)-3,4-dihydroxy-4-methyltetrahydrofuran-2-yl]methoxy}(4-chlorophenoxy)phosphoryl]amino}propanoate 在 Phenomenex Luna C₁₈⁽²⁾ 作用下， 以 二甲基亚砜 为溶剂， 以15%的产率得到ethyl (2S)-2-{[{[(2R,3R,4R,5R)-5-(4-amino-2-oxopyrimidin-1(2H)-yl)-3,4-dihydroxy-4-methyltetrahydrofuran-2-yl]methoxy}(4-chlorophenoxy)phosphoryl]amino}propanoate
  参考文献：
  名称：

  Cyclic phosphoramidates as prodrugs of 2′-C-methylcytidine

  摘要：

  The currently approved treatment for hepatitis C virus infections is a combination of Ribavirin and pegylated Interferon. It leads to a sustained virologic response in approximately only half of the patients treated. For this reason there is an urgent need of new therapeutic agents. 2'-C-Methylcytidine is the first nucleoside inhibitor of the HCV NS5B polymerase that was efficacious in reducing the viral load in patients infected with HCV. The application of a monophosphate prodrug approach based on unprecedented cyclic phosphoramidates is reported. Our SAR studies led to compounds that are efficiently converted to the active triphosphate in human hepatocytes. (C) 2009 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2009.04.043

文献信息

• Cyclic phosphoramidates as prodrugs of 2′-C-methylcytidine
  作者：Malte Meppen、Barbara Pacini、Renzo Bazzo、Uwe Koch、Joseph F. Leone、Kenneth A. Koeplinger、Michael Rowley、Sergio Altamura、Annalise Di Marco、Fabrizio Fiore、Claudio Giuliano、Odalys Gonzalez-Paz、Ralph Laufer、Vincenzo Pucci、Frank Narjes、Cristina Gardelli

  DOI：10.1016/j.ejmech.2009.04.043

  日期：2009.9

  The currently approved treatment for hepatitis C virus infections is a combination of Ribavirin and pegylated Interferon. It leads to a sustained virologic response in approximately only half of the patients treated. For this reason there is an urgent need of new therapeutic agents. 2'-C-Methylcytidine is the first nucleoside inhibitor of the HCV NS5B polymerase that was efficacious in reducing the viral load in patients infected with HCV. The application of a monophosphate prodrug approach based on unprecedented cyclic phosphoramidates is reported. Our SAR studies led to compounds that are efficiently converted to the active triphosphate in human hepatocytes. (C) 2009 Elsevier Masson SAS. All rights reserved.