6,7-dichloro-1-(2,3,5-tri-O-benzoyl-β-D-ribofuranosyl)imidazo<4,5-b>quinoxalin-2-thione | 213738-16-0

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 6,7-dichloro-1-(2,3,5-tri-O-benzoyl-β-D-ribofuranosyl)imidazo<4,5-b>quinoxalin-2-thione
• CAS: 213738-16-0
• 化学式: C₃₅H₂₄Cl₂N₄O₇S
• 分子量: 715.57
• InChiKey: ZZOCHAFVGHAOKI-QNCJLPSESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.15
• 重原子数：
  49.0
• 可旋转键数：
  8.0
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  134.63
• 氢给体数：
  1.0
• 氢受体数：
  11.0

反应信息

• 作为反应物：
  描述：

  6,7-dichloro-1-(2,3,5-tri-O-benzoyl-β-D-ribofuranosyl)imidazo<4,5-b>quinoxalin-2-thione 在 ammonium hydroxide 、 sodium methylate 作用下， 以 甲醇 、 水 为溶剂， 反应 4.0h， 生成 2-benzylthio-6,7-dichloro-1-(β-D-ribofuranosyl)imidazo<4,5-b>quinoxaline
  参考文献：
  名称：

  Synthesis of Imidazo[4,5-b]quinoxaline Ribonucleosides as Linear Dimensional Analogs of Antiviral Polyhalogenated Benzimidazole Ribonucleosides

  摘要：

  AbstractWe have recently found that 2,5,6‐trichloro‐1‐(β‐D‐ribofuranosyl)benzimidazole (TCRB) and the corresponding 2‐bromo analog have better in vitro activities against HCMV than the clinically used agents ganciclovir and foscarnet. These benzimidazole nucleosides act by a unique mechanism, however, their biological target has not been completely identified. As an approach to probing the target, we have designed imidazo[4,5‐b]quinoxaline nucleosides as linear dimensional analogs of the benzimidazole nucleosides to study the spatial limitation of the binding site in the target enzyme. A convenient route was developed for the synthesis of 2‐substituted 6,7‐dichloroimidazo[4,5‐b]quinoxalines involving a reaction of 2,3,6,7‐tetrachloroquinoxaline with ammonia followed by a ring annulation as the key step. This furnished the versatile heterocycle 6,7‐dichloroimidazo[4,5‐b]quinoxalin‐2‐one. Ribosylation of 2‐substituted imidazo[4,5‐b]quinoxalines was influenced by the functional group at the 2‐position and the 2‐one compound was found to smoothly undergo ribosylation. The 2‐one group of the nucleoside was converted into specifically selected 2‐substituted compounds. Evaluation of the compounds for activity against two herpesviruses and for cytotoxicity showed they were less active and/or more cytotoxic than TCRB. We conclude therefore, that the binding pocket on the protein target of TCRB will tolerate some electronic and size changes.

  DOI：

  10.1002/jccs.199800071
• 作为产物：
  描述：

  2,3,6,7-四氯喹喔啉 在 三氟甲磺酸三甲基硅酯 、 硫化氢 、 氨 、 牛血清白蛋白 、 三乙胺 、 三氯氧磷 作用下， 以 甲苯 、 乙腈 为溶剂， 反应 45.42h， 生成 6,7-dichloro-1-(2,3,5-tri-O-benzoyl-β-D-ribofuranosyl)imidazo<4,5-b>quinoxalin-2-thione
  参考文献：
  名称：

  Synthesis of Imidazo[4,5-b]quinoxaline Ribonucleosides as Linear Dimensional Analogs of Antiviral Polyhalogenated Benzimidazole Ribonucleosides

  摘要：

  AbstractWe have recently found that 2,5,6‐trichloro‐1‐(β‐D‐ribofuranosyl)benzimidazole (TCRB) and the corresponding 2‐bromo analog have better in vitro activities against HCMV than the clinically used agents ganciclovir and foscarnet. These benzimidazole nucleosides act by a unique mechanism, however, their biological target has not been completely identified. As an approach to probing the target, we have designed imidazo[4,5‐b]quinoxaline nucleosides as linear dimensional analogs of the benzimidazole nucleosides to study the spatial limitation of the binding site in the target enzyme. A convenient route was developed for the synthesis of 2‐substituted 6,7‐dichloroimidazo[4,5‐b]quinoxalines involving a reaction of 2,3,6,7‐tetrachloroquinoxaline with ammonia followed by a ring annulation as the key step. This furnished the versatile heterocycle 6,7‐dichloroimidazo[4,5‐b]quinoxalin‐2‐one. Ribosylation of 2‐substituted imidazo[4,5‐b]quinoxalines was influenced by the functional group at the 2‐position and the 2‐one compound was found to smoothly undergo ribosylation. The 2‐one group of the nucleoside was converted into specifically selected 2‐substituted compounds. Evaluation of the compounds for activity against two herpesviruses and for cytotoxicity showed they were less active and/or more cytotoxic than TCRB. We conclude therefore, that the binding pocket on the protein target of TCRB will tolerate some electronic and size changes.

  DOI：

  10.1002/jccs.199800071