(E)-4-((5-(3-(2-aminopyridin-4-yl)-2-oxoimidazolidin-1-yl)pentyl)oxy)benzaldehyde O-ethyl oxime

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: (E)-4-((5-(3-(2-aminopyridin-4-yl)-2-oxoimidazolidin-1-yl)pentyl)oxy)benzaldehyde O-ethyl oxime
• 英文别名: 1-(2-aminopyridin-4-yl)-3-[5-[4-[(E)-ethoxyiminomethyl]phenoxy]pentyl]imidazolidin-2-one
• 化学式: C₂₂H₂₉N₅O₃
• 分子量: 411.504
• InChiKey: AMOFBULALDHBLU-KOEQRZSOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  30
• 可旋转键数：
  11
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  93.3
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  (4-bromo-pyridin-2-yl)-bis-(4-methoxy-benzyl)-amine 在 tris-(dibenzylideneacetone)dipalladium(0) 、 sodium hydride 、 potassium carbonate 、 caesium carbonate 、 4,5-双二苯基膦-9,9-二甲基氧杂蒽 、 三氟乙酸 作用下， 以 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 22.0h， 生成 (E)-4-((5-(3-(2-aminopyridin-4-yl)-2-oxoimidazolidin-1-yl)pentyl)oxy)benzaldehyde O-ethyl oxime
  参考文献：
  名称：

  Design, Synthesis, and Evaluation of Novel Enterovirus 71 Inhibitors as Therapeutic Drug Leads for the Treatment of Human Hand, Foot, and Mouth Disease

  摘要：

  Human hand, foot, and mouth disease (HFMD) is a serious public health threat with high infection rates in children and infants who reside in Asia and the Pacific regions, and no effective drugs are currently available. Enterovirus 71 (EV71) and coxsackievirus A16 are the major etiological pathogens. Based on an essential hydrophobic pocket on the viral capsid protein VP1, we designed and synthesized a series of small molecular weight compounds as inhibitors of EV71. A potential drug candidate named NLD-22 exhibited excellent antiviral activity (with an EC50 of 5.056 nM and a 100% protection rate for mice at a dose of 20 mg/kg) and low toxicity. NLD-22 had a favorable pharmacokinetic profile. High-resolution cryo-electron microscopy structural analysis confirmed NLD-22 bound to the hydrophobic pocket in VP1 to block viral infection. In general, NLD-22 was indicated to be a promising potential drug candidate for the treatment of HFMD.

  DOI：

  10.1021/acs.jmedchem.9b01414