4-methyl-7-(2,3-O-isopropylidene-5-O-methyl-β-D-ribofuranosyl)pyrrolo[2,3-d]pyrimidine | 1256159-15-5

• 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-O-isopropylidene-5-O-methyl-β-D-ribofuranosyl)pyrrolo[2,3-d]pyrimidine
• 英文别名: 7-deaza-6-methyl-9-(2,3-O-isopropylidene-5-O-methyl-β-D-ribofuranosyl)purine；7-[(3aR,4R,6R,6aR)-6-(methoxymethyl)-2,2-dimethyl-3a,4,6,6a-tetrahydrofuro[3,4-d][1,3]dioxol-4-yl]-4-methylpyrrolo[2,3-d]pyrimidine
• CAS: 1256159-15-5
• 化学式: C₁₆H₂₁N₃O₄
• 分子量: 319.36
• InChiKey: XINMJSIGTZZDGM-RGCMKSIDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  23
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  67.6
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  4-methyl-7-(2,3-O-isopropylidene-5-O-methyl-β-D-ribofuranosyl)pyrrolo[2,3-d]pyrimidine 在 三氟乙酸 作用下， 以 水 为溶剂， 反应 0.25h， 以87%的产率得到4-methyl-7-(5-O-methyl-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
• 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 、 氨 、 sodium hydride 、 对甲苯磺酸 作用下， 以 四氢呋喃 、 甲醇 、 正己烷 、 丙酮 、 乙腈 为溶剂， 反应 17.83h， 生成 4-methyl-7-(2,3-O-isopropylidene-5-O-methyl-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

文献信息

• Synthesis of a 6-Methyl-7-deaza Analogue of Adenosine That Potently Inhibits Replication of Polio and Dengue Viruses
  作者：Runzhi Wu、Eric D. Smidansky、Hyung Suk Oh、Ratree Takhampunya、Radhakrishnan Padmanabhan、Craig E. Cameron、Blake R. Peterson

  DOI：10.1021/jm100593s

  日期：2010.11.25

  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.