N-(4-amino-2-(methylamino)-6-oxo-1,6-dihydropyrimidin-5-yl)-2-(4-chlorophenoxy)acetamide | 1373822-33-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: N-(4-amino-2-(methylamino)-6-oxo-1,6-dihydropyrimidin-5-yl)-2-(4-chlorophenoxy)acetamide
• 英文别名: N-[4-amino-2-(methylamino)-6-oxo-1H-pyrimidin-5-yl]-2-(4-chlorophenoxy)acetamide
• CAS: 1373822-33-3
• 化学式: C₁₃H₁₄ClN₅O₃
• 分子量: 323.739
• InChiKey: BUPBFOAAXRJPLQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.3
• 重原子数：
  22
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  118
• 氢给体数：
  4
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  N-(4-amino-2-(methylamino)-6-oxo-1,6-dihydropyrimidin-5-yl)-2-(4-chlorophenoxy)acetamide 在 硼烷四氢呋喃络合物 作用下， 以 四氢呋喃 为溶剂， 反应 1.08h， 以54%的产率得到6-amino-5-(2-(4-chlorophenoxy)ethylamino)-2-(methylamino)-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
• 作为产物：
  描述：

  4-氯苯氧基乙酰氯 、 5,6-diamino-2-methylamino-4(3H)-pyrimidone 在 potassium carbonate 作用下， 以 二氯甲烷 为溶剂， 以66%的产率得到N-(4-amino-2-(methylamino)-6-oxo-1,6-dihydropyrimidin-5-yl)-2-(4-chlorophenoxy)acetamide
  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.