1-(3,4-didehydro-2,3-dideoxy-β-D-pentofuranosyl-4-carboxymethyl)thymine | 1558010-72-2

• 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-(3,4-didehydro-2,3-dideoxy-β-D-pentofuranosyl-4-carboxymethyl)thymine
• 英文别名: methyl (2R)-2-(5-methyl-2,4-dioxo-pyrimidin-1-yl)-2,3-dihydrofuran-5-carboxylate；methyl (2R)-2-(5-methyl-2,4-dioxopyrimidin-1-yl)-2,3-dihydrofuran-5-carboxylate
• CAS: 1558010-72-2
• 化学式: C₁₁H₁₂N₂O₅
• 分子量: 252.227
• InChiKey: HSLTXTOYOVLTEH-MRVPVSSYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.4
• 重原子数：
  18
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  84.9
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  1-(3,4-didehydro-2,3-dideoxy-β-D-pentofuranosyl-4-carboxymethyl)thymine 在 ammonium hydroxide 作用下， 以 水 为溶剂， 反应 0.5h， 生成 1-(3,4-didehydro-2,3-dideoxy-β-D-pentofuranosyl-4-carboxamido)thymine
  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 、 5-(5-methyl-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4,5-dihydro-furan-2-carboxylic acid 在 硫酸 作用下， 反应 5.0h， 以60%的产率得到1-(3,4-didehydro-2,3-dideoxy-β-D-pentofuranosyl-4-carboxymethyl)thymine
  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.