1-(2-deoxy-2-fluoro-β-D-arabinopentofuranosyl-4-carboxymethyl)-5-ethyluracil | 1558010-61-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: 1-(2-deoxy-2-fluoro-β-D-arabinopentofuranosyl-4-carboxymethyl)-5-ethyluracil
• 英文别名: methyl (2S,3R,4S,5R)-5-(5-ethyl-2,4-dioxo-pyrimidin-1-yl)-4-fluoro-3-hydroxy-tetrahydrofuran-2-carboxylate；methyl (2S,3R,4S,5R)-5-(5-ethyl-2,4-dioxopyrimidin-1-yl)-4-fluoro-3-hydroxyoxolane-2-carboxylate
• CAS: 1558010-61-9
• 化学式: C₁₂H₁₅FN₂O₆
• 分子量: 302.259
• InChiKey: SVGROOYHYNBYPD-AZQAYCESSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.1
• 重原子数：
  21
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  105
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  1-(2-deoxy-2-fluoro-β-D-arabinopentofuranosyl-4-carboxymethyl)-5-ethyluracil 在 ammonium hydroxide 作用下， 以 水 为溶剂， 反应 0.5h， 以97%的产率得到1-(2-deoxy-2-fluoro-β-D-arabinopentofuranosyl-4-carboxamido)-5-ethyluracil
  参考文献：
  名称：

  4′-Substituted pyrimidine nucleosides lacking 5′-hydroxyl function as potential anti-HCV agents

  摘要：

  Hepatitis C virus (HCV) infection is one of the major health problems worldwide. If left untreated, it leads to liver cirrhosis, liver cancer and death. Herein, we report synthesis and anti-HCV activity of a new class of pyrimidine nucleosides possessing a 4'-carboxymethyl (9-16, 21 and 23) or 4'-carboxamide function (17-19 and 24). Among these, 10-12 (EC50 = 33.1-42.4 mu M), 14 and 21 (EC50 = 43.4-59.5 mu M) exhibited potent activity in HCV-1a replicon cells without any toxicity to parent Huh-7 cells (CC50 = > 829-1055 mu M). The anti-HCV activities demonstrated by this unusual class of compounds were superior to that of ribavirin (EC50 = 81.9 lM). Further, the most active analog, 12, was found to interact synergistically with ribavirin to inhibit HCV RNA replication. (C) 2014 Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmcl.2014.01.024
• 作为产物：
  描述：

  甲醇 、 1-(2-deoxy-2-fluoro-5-oxo-β-D-arabinofuranosyl)-5-ethyluracil 在 硫酸 作用下， 反应 5.0h， 以72%的产率得到1-(2-deoxy-2-fluoro-β-D-arabinopentofuranosyl-4-carboxymethyl)-5-ethyluracil
  参考文献：
  名称：

  4′-Substituted pyrimidine nucleosides lacking 5′-hydroxyl function as potential anti-HCV agents

  摘要：

  Hepatitis C virus (HCV) infection is one of the major health problems worldwide. If left untreated, it leads to liver cirrhosis, liver cancer and death. Herein, we report synthesis and anti-HCV activity of a new class of pyrimidine nucleosides possessing a 4'-carboxymethyl (9-16, 21 and 23) or 4'-carboxamide function (17-19 and 24). Among these, 10-12 (EC50 = 33.1-42.4 mu M), 14 and 21 (EC50 = 43.4-59.5 mu M) exhibited potent activity in HCV-1a replicon cells without any toxicity to parent Huh-7 cells (CC50 = > 829-1055 mu M). The anti-HCV activities demonstrated by this unusual class of compounds were superior to that of ribavirin (EC50 = 81.9 lM). Further, the most active analog, 12, was found to interact synergistically with ribavirin to inhibit HCV RNA replication. (C) 2014 Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmcl.2014.01.024

文献信息

• 4′-Substituted pyrimidine nucleosides lacking 5′-hydroxyl function as potential anti-HCV agents
  作者：Neeraj Shakya、Satish Vedi、Chao Liang、Fang Yang、Babita Agrawal、Rakesh Kumar

  DOI：10.1016/j.bmcl.2014.01.024

  日期：2014.3

  Hepatitis C virus (HCV) infection is one of the major health problems worldwide. If left untreated, it leads to liver cirrhosis, liver cancer and death. Herein, we report synthesis and anti-HCV activity of a new class of pyrimidine nucleosides possessing a 4'-carboxymethyl (9-16, 21 and 23) or 4'-carboxamide function (17-19 and 24). Among these, 10-12 (EC50 = 33.1-42.4 mu M), 14 and 21 (EC50 = 43.4-59.5 mu M) exhibited potent activity in HCV-1a replicon cells without any toxicity to parent Huh-7 cells (CC50 = > 829-1055 mu M). The anti-HCV activities demonstrated by this unusual class of compounds were superior to that of ribavirin (EC50 = 81.9 lM). Further, the most active analog, 12, was found to interact synergistically with ribavirin to inhibit HCV RNA replication. (C) 2014 Published by Elsevier Ltd.