9-(2',3',5'-tri-O-acetyl-β-D-ribofuranos-1'-yl)purine-8-thione | 157025-59-7

• 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: 9-(2',3',5'-tri-O-acetyl-β-D-ribofuranos-1'-yl)purine-8-thione
• 英文别名: 9-(2,3,5-tri-O-acetyl-β-D-ribofuranosyl)purine-8(7H)-thione；[(2R,3R,4R,5R)-3,4-diacetoxy-5-(8-thioxo-7H-purin-9-yl)tetrahydrofuran-2-yl]methyl acetate；[(2R,3R,4R,5R)-3,4-diacetyloxy-5-(8-sulfanylidene-7H-purin-9-yl)oxolan-2-yl]methyl acetate
• CAS: 157025-59-7
• 化学式: C₁₆H₁₈N₄O₇S
• 分子量: 410.408
• InChiKey: CCCGSYUDUOJNHR-RGCMKSIDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.4
• 重原子数：
  28
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  161
• 氢给体数：
  1
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  9-(2',3',5'-tri-O-acetyl-β-D-ribofuranos-1'-yl)purine-8-thione 在 氨 、 对甲苯磺酸 作用下， 以 甲醇 、 丙酮 为溶剂， 反应 60.0h， 生成 9-(2',3'-O-isopropylidene-β-D-ribofuranos-1'-yl)purine-8-thione
  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
• 作为产物：
  描述：

  (2R,3R,4R,5R)-2-(acetoxymethyl)-5-(8-bromo-9H-purin-9-yl)tetrahydrofuran-3,4-diyl diacetate 在 triourea 作用下， 以 乙醇 为溶剂， 反应 5.0h， 以83%的产率得到9-(2',3',5'-tri-O-acetyl-β-D-ribofuranos-1'-yl)purine-8-thione
  参考文献：
  名称：

  Synthesis and Biologic Evaluation of 8-Substituted Derivatives of Nebularine (9-β-D-Ribofuranosylpurine)

  摘要：

  A series of 8-substituted purine ribonucleosides were prepared from 2',3',5'-tri-O-acetyl-8-bromoadenosine and evaluated for cytotoxicity and antiviral activity. Four of these nucleosides (6b-9b) were significantly toxic to both HEp-2 and L1210 cells in culture but the most cytotoxic one (9b) was inactive against the P388 leukemia in mice. None of these nucleosides showed significant antiviral activity against Herpes Simplex 1 or 2, vaccinia, or influenza A.

  DOI：

  10.1080/15257779408011875

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.
• Synthesis and Biologic Evaluation of 8-Substituted Derivatives of Nebularine (9-β-D-Ribofuranosylpurine)
  作者：John A. Secrist、Anita Shortnacy-Fowler、L. Lee Bennett、John A. Montgomery

  DOI：10.1080/15257779408011875

  日期：1994.6

  A series of 8-substituted purine ribonucleosides were prepared from 2',3',5'-tri-O-acetyl-8-bromoadenosine and evaluated for cytotoxicity and antiviral activity. Four of these nucleosides (6b-9b) were significantly toxic to both HEp-2 and L1210 cells in culture but the most cytotoxic one (9b) was inactive against the P388 leukemia in mice. None of these nucleosides showed significant antiviral activity against Herpes Simplex 1 or 2, vaccinia, or influenza A.