4-((1,5-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)amino)-N-(2-methoxyethyl)-5-methylthieno[2,3-d]pyrimidine-6-carboxamide

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 噻吩并嘧啶酮衍生物
• 英文名称: 4-((1,5-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)amino)-N-(2-methoxyethyl)-5-methylthieno[2,3-d]pyrimidine-6-carboxamide
• 英文别名: 4-[(1,5-dimethyl-2-oxopyridin-3-yl)amino]-N-(2-methoxyethyl)-5-methylthieno[2,3-d]pyrimidine-6-carboxamide
• 化学式: C₁₈H₂₁N₅O₃S
• 分子量: 387.462
• InChiKey: ZIGVXGJXOFYHOU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  27
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  125
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  4-氯-5-甲基噻吩并[2,3-d]嘧啶-6-羧酸甲酯 在 水 、 对甲苯磺酸 、 N,N-二异丙基乙胺 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 、 sodium hydroxide 作用下， 以 1,4-二氧六环 、 甲醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 2.67h， 生成 4-((1,5-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)amino)-N-(2-methoxyethyl)-5-methylthieno[2,3-d]pyrimidine-6-carboxamide
  参考文献：
  名称：

  Discovery of 4-(dihydropyridinon-3-yl)amino-5-methylthieno[2,3-d]pyrimidine derivatives as potent Mnk inhibitors: synthesis, structure–activity relationship analysis and biological evaluation

  摘要：

  Phosphorylation of the eukaryotic initiation factor 4E (eIF4E) by mitogen-activated protein kinase (MAPK)-interacting kinases (Mnks) is essential for oncogenesis but unnecessary for normal development. Thus, pharmacological inhibition of Mnks may offer an effective and non-toxic anti-cancer therapeutic strategy. Herein, we report the discovery of 4-(dihydropyridinon-3-yl)amino-5-methylthieno[2,3-d]pyrimidine derivatives as potent Mnk inhibitors. Docking study of 7a in Mnk2 suggests that the compound is stabilised in the ATP binding site through multiple hydrogen bonds and hydrophobic interaction. Cellular mechanistic studies on MV-4-11 cells with leads 7a, 8e and 8f reveal that they are able to down-regulate the phosphorylated eIF4E, Mcl-1 and cyclin D1, and induce apoptosis. (C) 2015 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2015.03.032