(E)-2-cyano-N-cyclopropyl-3-(5-morpholin-4-yl-2-furyl)acrylamide | 1352550-40-3

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: (E)-2-cyano-N-cyclopropyl-3-(5-morpholin-4-yl-2-furyl)acrylamide
• 英文别名: (E)-2-cyano-N-cyclopropyl-3-(5-morpholin-4-ylfuran-2-yl)prop-2-enamide
• CAS: 1352550-40-3
• 化学式: C₁₅H₁₇N₃O₃
• 分子量: 287.318
• InChiKey: ZSQADYPIOXKUEJ-PKNBQFBNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  21
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  78.5
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  5-溴-2-呋喃甲醛 、 2-氰基-N-环丙基乙酰胺 在 N-甲基哌嗪 、 copper(l) iodide 、 potassium carbonate 、 L-脯氨酸 作用下， 以 甲醇 、 二甲基亚砜 为溶剂， 反应 20.0h， 生成 (E)-2-cyano-N-cyclopropyl-3-(5-morpholin-4-yl-2-furyl)acrylamide
  参考文献：
  名称：

  Arylcyanoacrylamides as inhibitors of the Dengue and West Nile virus proteases

  摘要：

  The 3-aryl-2-cyanoacrylamide scaffold was designed as core pharmacophore for inhibitors of the Dengue and West Nile virus serine proteases (NS2B-NS3). A total of 86 analogs was prepared to study the structure-activity relationships in detail. Thereby, it turned out that the electron density of the aryl moiety and the central double bond have a crucial influence on the activity of the compounds, whereas the influence of substituents of the amide residue is less relevant. The para-hydroxy substituted analog was found to be the most potent inhibitor in this series with a K(i)-value of 35.7 mu M at the Dengue and 44.6 mu M at the West Nile virus protease. The aprotinin competition assay demonstrates a direct interaction of the inhibitor molecule with active centre of the Dengue virus protease. The target selectivity was studied in a counterscreen with thrombin and found to be 2.8:1 in favor of DEN protease and 2.3:1 in favor of WNV protease, respectively. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.10.061

文献信息

• Arylcyanoacrylamides as inhibitors of the Dengue and West Nile virus proteases
  作者：Christoph Nitsche、Christian Steuer、Christian D. Klein

  DOI：10.1016/j.bmc.2011.10.061

  日期：2011.12

  The 3-aryl-2-cyanoacrylamide scaffold was designed as core pharmacophore for inhibitors of the Dengue and West Nile virus serine proteases (NS2B-NS3). A total of 86 analogs was prepared to study the structure-activity relationships in detail. Thereby, it turned out that the electron density of the aryl moiety and the central double bond have a crucial influence on the activity of the compounds, whereas the influence of substituents of the amide residue is less relevant. The para-hydroxy substituted analog was found to be the most potent inhibitor in this series with a K(i)-value of 35.7 mu M at the Dengue and 44.6 mu M at the West Nile virus protease. The aprotinin competition assay demonstrates a direct interaction of the inhibitor molecule with active centre of the Dengue virus protease. The target selectivity was studied in a counterscreen with thrombin and found to be 2.8:1 in favor of DEN protease and 2.3:1 in favor of WNV protease, respectively. (C) 2011 Elsevier Ltd. All rights reserved.