4-methyl-7-(2,3,5-tri-O-acetyl-β-D-ribofuranosyl)pyrrolo[2,3-d]pyrimidine | 1256159-13-3

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 吡咯并嘧啶核苷和核苷酸
• 英文名称: 4-methyl-7-(2,3,5-tri-O-acetyl-β-D-ribofuranosyl)pyrrolo[2,3-d]pyrimidine
• 英文别名: 7-deaza-6-methyl-9-(2,3,5-tri-O-acetyl-β-D-ribofuranosyl)purine；[(2R,3R,4R,5R)-3,4-diacetyloxy-5-(4-methylpyrrolo[2,3-d]pyrimidin-7-yl)oxolan-2-yl]methyl acetate
• CAS: 1256159-13-3
• 化学式: C₁₈H₂₁N₃O₇
• 分子量: 391.381
• InChiKey: RJOWXWGAPJLZOQ-YFHUEUNASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 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：
  119
• 氢给体数：
  0
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  4-methyl-7-(2,3,5-tri-O-acetyl-β-D-ribofuranosyl)pyrrolo[2,3-d]pyrimidine 在 氨 、 对甲苯磺酸 、 三氯化磷 作用下， 以 甲醇 、 二氯甲烷 、 水 、 丙酮 为溶剂， 反应 9.66h， 生成 7-deaza-6-methyl-9-β-D-ribofuranosylpurine 5'-phosphonate triethylamine salt 1:1
  参考文献：
  名称：

  Synthesis of a 6-Methyl-7-deaza Analogue of Adenosine That Potently Inhibits Replication of Polio and Dengue Viruses

  摘要：

  Bioisosteric deaza analogues of 6-methyl-9-beta-D-ribofuranosylpurine, a hydrophobic analogue of adenosine, were synthesized and evaluated for antiviral activity. Whereas the 1-deaza and 3-deaza analogues were essentially inactive in plaque assays of infectivity, a novel 7-deaza-6-methyl-9-beta-D-ribofuranosylpurine analogue, structurally related to the natural product tubercidin, potently inhibited replication of poliovirus (PV) in HeLa cells (IC50 = 11 nM) and dengue virus (DENV) in Vero cells (IC50 = 62 nM). Selectivity against PV over cytotoxic effects to HeLa cells was > 100-fold after incubation for 7 h. Mechanistic studies of the 5'-triphosphate of 7-deaza-6-methyl-9-beta-D-riboluranosylpurine revealed that this compound is an efficient substrate of PV RNA-dependent RNA polymerase (RdRP) and is incorporated into RNA mimicking both ATP and GTP.

  DOI：

  10.1021/jm100593s
• 作为产物：
  描述：

  4-chloro-7-β-D-ribofuranosylpyrrolo<2,3-d>pyrimidine 在 吡啶 、 四(三苯基膦)钯 作用下， 以 四氢呋喃 、 正己烷 为溶剂， 反应 11.0h， 生成 4-methyl-7-(2,3,5-tri-O-acetyl-β-D-ribofuranosyl)pyrrolo[2,3-d]pyrimidine
  参考文献：
  名称：

  Synthesis of a 6-Methyl-7-deaza Analogue of Adenosine That Potently Inhibits Replication of Polio and Dengue Viruses

  摘要：

  Bioisosteric deaza analogues of 6-methyl-9-beta-D-ribofuranosylpurine, a hydrophobic analogue of adenosine, were synthesized and evaluated for antiviral activity. Whereas the 1-deaza and 3-deaza analogues were essentially inactive in plaque assays of infectivity, a novel 7-deaza-6-methyl-9-beta-D-ribofuranosylpurine analogue, structurally related to the natural product tubercidin, potently inhibited replication of poliovirus (PV) in HeLa cells (IC50 = 11 nM) and dengue virus (DENV) in Vero cells (IC50 = 62 nM). Selectivity against PV over cytotoxic effects to HeLa cells was > 100-fold after incubation for 7 h. Mechanistic studies of the 5'-triphosphate of 7-deaza-6-methyl-9-beta-D-riboluranosylpurine revealed that this compound is an efficient substrate of PV RNA-dependent RNA polymerase (RdRP) and is incorporated into RNA mimicking both ATP and GTP.

  DOI：

  10.1021/jm100593s