4-(2-(benzylthio)-7-(2-(4-chlorophenoxy)ethyl)-6-oxo-6,7-dihydro-1Hpurin-8-yl)benzylphosphonic acid | 1373822-52-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 4-(2-(benzylthio)-7-(2-(4-chlorophenoxy)ethyl)-6-oxo-6,7-dihydro-1Hpurin-8-yl)benzylphosphonic acid
• CAS: 1373822-52-6
• 化学式: C₂₇H₂₄ClN₄O₅PS
• 分子量: 583.004
• InChiKey: BHHGJTBLICAKBW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.49
• 重原子数：
  39.0
• 可旋转键数：
  10.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  130.33
• 氢给体数：
  3.0
• 氢受体数：
  7.0

反应信息

• 作为反应物：
  描述：

  4-(2-(benzylthio)-7-(2-(4-chlorophenoxy)ethyl)-6-oxo-6,7-dihydro-1Hpurin-8-yl)benzylphosphonic acid 、 甲胺 以 水 为溶剂， 反应 12.0h， 以68%的产率得到(4-(7-(2-(4-chlorophenoxy)ethyl)-2-(methylamino)-6-oxo-6,7-dihydro-1H-purin-8-yl)benzyl)phosphonic acid
  参考文献：
  名称：

  Structure-Guided Design, Synthesis, and Evaluation of Guanine-Derived Inhibitors of the eIF4E mRNA–Cap Interaction

  摘要：

  The eukaryotic initiation factor 4E (eIF4E) plays a central role in the initiation of gene translation and subsequent protein synthesis by binding the 5' terminal mRNA cap structure. We designed and synthesized a series of novel compounds that display potent binding affinity against eIF4E despite their lack of a ribose moiety, phosphate, and positive charge as present in m7-GMP. The biochemical activity of compound 33 is 95 nM for eIF4E in an SPA binding assay. More importantly, the compound has an IC50 of 2.5 mu M for inhibiting cap-dependent mRNA translation in a rabbit reticular cell extract assay (RRL-IVT). This series of potent, truncated analogues could serve as a promising new starting point toward the design of neutral eIF4E inhibitors with physicochemical properties suitable for cellular activity assessment.

  DOI：

  10.1021/jm300037x
• 作为产物：
  描述：

  methyl hydrogen 4-(2-(benzylthio)-7-(2-(4-chlorophenoxy)ethyl)-6-oxo-6,7-dihydro-1H-purin-8-yl)benzylphosphonate 在 甲醇 、 三甲基溴硅烷 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 72.0h， 以0.143 g的产率得到4-(2-(benzylthio)-7-(2-(4-chlorophenoxy)ethyl)-6-oxo-6,7-dihydro-1Hpurin-8-yl)benzylphosphonic acid
  参考文献：
  名称：

  Structure-Guided Design, Synthesis, and Evaluation of Guanine-Derived Inhibitors of the eIF4E mRNA–Cap Interaction

  摘要：

  The eukaryotic initiation factor 4E (eIF4E) plays a central role in the initiation of gene translation and subsequent protein synthesis by binding the 5' terminal mRNA cap structure. We designed and synthesized a series of novel compounds that display potent binding affinity against eIF4E despite their lack of a ribose moiety, phosphate, and positive charge as present in m7-GMP. The biochemical activity of compound 33 is 95 nM for eIF4E in an SPA binding assay. More importantly, the compound has an IC50 of 2.5 mu M for inhibiting cap-dependent mRNA translation in a rabbit reticular cell extract assay (RRL-IVT). This series of potent, truncated analogues could serve as a promising new starting point toward the design of neutral eIF4E inhibitors with physicochemical properties suitable for cellular activity assessment.

  DOI：

  10.1021/jm300037x