8-(6'-chlorocoumarin-3'-yl)methylthio-9-(2'',3'',5''-tri-O-acetyl-β-D-ribofuranos-1''-yl)purine | 1274898-41-7

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘌呤核苷
• 英文名称: 8-(6'-chlorocoumarin-3'-yl)methylthio-9-(2'',3'',5''-tri-O-acetyl-β-D-ribofuranos-1''-yl)purine
• 英文别名: [(2R,3R,4R,5R)-3,4-diacetyloxy-5-[8-[(6-chloro-2-oxochromen-3-yl)methylsulfanyl]purin-9-yl]oxolan-2-yl]methyl acetate
• CAS: 1274898-41-7
• 化学式: C₂₆H₂₃ClN₄O₉S
• 分子量: 603.009
• InChiKey: IEXQNFOQPOZYCD-GBEXAXCTSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  41
• 可旋转键数：
  11
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  183
• 氢给体数：
  0
• 氢受体数：
  13

反应信息

• 作为产物：
  描述：

  四乙酰核糖 在 N,O-双三甲硅基乙酰胺 、 氨 作用下， 以 水 、 乙腈 为溶剂， 反应 21.0h， 生成 8-(6'-chlorocoumarin-3'-yl)methylthio-9-(2'',3'',5''-tri-O-acetyl-β-D-ribofuranos-1''-yl)purine
  参考文献：
  名称：

  Coumarin−Purine Ribofuranoside Conjugates as New Agents against Hepatitis C Virus

  摘要：

  About 3% of world's population is infected by the hepatitis C virus (HCV), for which prophylactic vaccine is not available yet. Nowadays, pegylated interferon-a and ribavirin are commonly used to treat HCV; unfortunately these drugs often produce significant side effects. Upon the desperate need of anti-HCV drugs, a plan to establish a new compound library was set that included leads with high antiviral activity, good hydrophilicity, yet low toxicity. Accordingly, 26 new conjugated compounds were synthesized through the chemical coupling of various 9-(beta-D-ribofuranosyl)purine-8-thiones with 3-(chloromethyl)coumarins bearing various substitucnts. A -SCH2- unit was used to link the coumarin and the purine moieties. The three hydroxyl groups at the 2'-, 3'-, and 5'-positions were selectively protected with an acyl or acetal group in these coumarin-purine ribofuranosides. Their anti-HCV and cytostatic determination assays were performed, and the structure activity relationship was established. Three conjugates in the family of 8-(coumarin-3'-yl)methylthio-9-(beta-D-ribofuranos-1 ''-yl)purine possessed an appealing ability to inhibit HCV replication with EC50 between 5.5 and 6.6 mu M and EC90 of similar to 20 mu M. These data in the new compound library provide clues for the future in the development of anti-HCV leads for viral eradication.

  DOI：

  10.1021/jm101337v

文献信息

• Coumarin−Purine Ribofuranoside Conjugates as New Agents against Hepatitis C Virus
  作者：Jih Ru Hwu、Shu-Yu Lin、Shwu-Chen Tsay、Erik De Clercq、Pieter Leyssen、Johan Neyts

  DOI：10.1021/jm101337v

  日期：2011.4.14

  About 3% of world's population is infected by the hepatitis C virus (HCV), for which prophylactic vaccine is not available yet. Nowadays, pegylated interferon-a and ribavirin are commonly used to treat HCV; unfortunately these drugs often produce significant side effects. Upon the desperate need of anti-HCV drugs, a plan to establish a new compound library was set that included leads with high antiviral activity, good hydrophilicity, yet low toxicity. Accordingly, 26 new conjugated compounds were synthesized through the chemical coupling of various 9-(beta-D-ribofuranosyl)purine-8-thiones with 3-(chloromethyl)coumarins bearing various substitucnts. A -SCH2- unit was used to link the coumarin and the purine moieties. The three hydroxyl groups at the 2'-, 3'-, and 5'-positions were selectively protected with an acyl or acetal group in these coumarin-purine ribofuranosides. Their anti-HCV and cytostatic determination assays were performed, and the structure activity relationship was established. Three conjugates in the family of 8-(coumarin-3'-yl)methylthio-9-(beta-D-ribofuranos-1 ''-yl)purine possessed an appealing ability to inhibit HCV replication with EC50 between 5.5 and 6.6 mu M and EC90 of similar to 20 mu M. These data in the new compound library provide clues for the future in the development of anti-HCV leads for viral eradication.