6-amino-2-(benzylthio)-5-(2-(4-chlorophenoxy)ethylamino)-pyrimidin-4(3H)-one | 1373822-41-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 6-amino-2-(benzylthio)-5-(2-(4-chlorophenoxy)ethylamino)-pyrimidin-4(3H)-one
• 英文别名: 4-amino-2-benzylsulfanyl-5-[2-(4-chlorophenoxy)ethylamino]-1H-pyrimidin-6-one
• CAS: 1373822-41-3
• 化学式: C₁₉H₁₉ClN₄O₂S
• 分子量: 402.904
• InChiKey: KACLQZUFRFJSPH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  27
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.16
• 拓扑面积：
  114
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  6-amino-2-(benzylthio)-5-(2-(4-chlorophenoxy)ethylamino)-pyrimidin-4(3H)-one 在 甲醇 、 4-二甲氨基吡啶 、 三甲基溴硅烷 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 73.0h， 生成 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
• 作为产物：
  描述：

  p-chlorophenoxyacetaldehyde 在 三乙酰氧基硼氢化钠 作用下， 以 二氯甲烷 为溶剂， 反应 1.0h， 生成 6-amino-2-(benzylthio)-5-(2-(4-chlorophenoxy)ethylamino)-pyrimidin-4(3H)-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

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.