(6-(2-amino-7-(2-(4-chlorophenoxy)ethyl)-6-oxo-1H-purin-7-ium-9(6H)-yl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]-dioxol-4-yl)methyl phosphate | 1373822-31-1

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘌呤核苷酸
• 英文名称: (6-(2-amino-7-(2-(4-chlorophenoxy)ethyl)-6-oxo-1H-purin-7-ium-9(6H)-yl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]-dioxol-4-yl)methyl phosphate
• 英文别名: [(3aR,4R,6R,6aR)-4-[2-amino-7-[2-(4-chlorophenoxy)ethyl]-6-oxo-1H-purin-9-ium-9-yl]-2,2-dimethyl-3a,4,6,6a-tetrahydrofuro[3,4-d][1,3]dioxol-6-yl]methyl hydrogen phosphate
• CAS: 1373822-31-1
• 化学式: C₂₁H₂₅ClN₅O₉P
• 分子量: 557.884
• InChiKey: PYFSHRHJFPDMPM-NVQRDWNXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.5
• 重原子数：
  37
• 可旋转键数：
  8
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  183
• 氢给体数：
  3
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  2-amino-7-(2-(4-chlorophenoxy)ethyl)-9-((3aR,4R,6R,6aR)-6-(hydroxymethyl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl)-6-oxo-6,9-dihydro-1H-purin-7-ium 在 磷酸三甲酯 、 三氯氧磷 作用下， 反应 0.5h， 生成 (6-(2-amino-7-(2-(4-chlorophenoxy)ethyl)-6-oxo-1H-purin-7-ium-9(6H)-yl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]-dioxol-4-yl)methyl phosphate
  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.