4-(7-(2-(4-chlorophenoxy)ethyl)-6-hydroxy-2-(methylamino)-7Hpurin-8-yl)phenylphosphonic acid | 1373822-39-9

• 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-(7-(2-(4-chlorophenoxy)ethyl)-6-hydroxy-2-(methylamino)-7Hpurin-8-yl)phenylphosphonic acid
• 英文别名: (4-{7-[2-(4-Chlorophenoxy)ethyl]-2-(Methylamino)-6-Oxo-6,7-Dihydro-1h-Purin-8-Yl}phenyl)phosphonic Acid；[4-[7-[2-(4-chlorophenoxy)ethyl]-2-(methylamino)-6-oxo-1H-purin-8-yl]phenyl]phosphonic acid
• CAS: 1373822-39-9
• 化学式: C₂₀H₁₉ClN₅O₅P
• 分子量: 475.828
• InChiKey: MCYZBWKMUOPJOU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  32
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  138
• 氢给体数：
  4
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  4-氯苯氧基乙酰氯 在 硼烷四氢呋喃络合物 、 三甲基溴硅烷 、 dicyclohexylmethylamine 、 palladium diacetate 、 potassium carbonate 、 sodium t-butanolate 作用下， 以 四氢呋喃 、 乙醇 、 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 73.58h， 生成 4-(7-(2-(4-chlorophenoxy)ethyl)-6-hydroxy-2-(methylamino)-7Hpurin-8-yl)phenylphosphonic 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

文献信息

• Structure-Guided Design, Synthesis, and Evaluation of Guanine-Derived Inhibitors of the eIF4E mRNA–Cap Interaction
  作者：Xiaoqi Chen、David J. Kopecky、Jeff Mihalic、Shawn Jeffries、Xiaoshan Min、Julie Heath、Jeff Deignan、SuJen Lai、Zice Fu、Cristiano Guimaraes、Shanling Shen、Shyun Li、Sheree Johnstone、Stephen Thibault、Haoda Xu、Mario Cardozo、Wang Shen、Nigel Walker、Frank Kayser、Zhulun Wang

  DOI：10.1021/jm300037x

  日期：2012.4.26

  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.