8-(4-bromophenyl)-7-(2-(4-chlorophenoxy)ethyl)-2-(methylamino)-1H-purin-6(7H)-one | 1373822-37-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 8-(4-bromophenyl)-7-(2-(4-chlorophenoxy)ethyl)-2-(methylamino)-1H-purin-6(7H)-one
• 英文别名: 8-(4-bromophenyl)-7-[2-(4-chlorophenoxy)ethyl]-2-(methylamino)-1H-purin-6-one
• CAS: 1373822-37-7
• 化学式: C₂₀H₁₇BrClN₅O₂
• 分子量: 474.744
• InChiKey: AKKYPGUIKXETKO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  29
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  80.5
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  8-(4-bromophenyl)-7-(2-(4-chlorophenoxy)ethyl)-2-(methylamino)-1H-purin-6(7H)-one 在 三甲基溴硅烷 、 dicyclohexylmethylamine 、 palladium diacetate 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 反应 24.0h， 生成 ethyl hydrogen (4-(7-(2-(4-chlorophenoxy)ethyl)-6-hydroxy-2-(methylamino)-7H-purin-8-yl)phenyl)phosphonate
  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：

  4-氯苯氧基乙酰氯 在 硼烷四氢呋喃络合物 、 potassium carbonate 、 sodium t-butanolate 作用下， 以 四氢呋喃 、 二氯甲烷 、 1,2-二氯乙烷 、 N,N-二甲基甲酰胺 、 异丙醇 为溶剂， 反应 1.58h， 生成 8-(4-bromophenyl)-7-(2-(4-chlorophenoxy)ethyl)-2-(methylamino)-1H-purin-6(7H)-one
  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