2-[Cyanomethyl-(4-nitronaphthalen-1-yl)amino]acetonitrile | 1417737-75-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 2-[Cyanomethyl-(4-nitronaphthalen-1-yl)amino]acetonitrile
• 英文别名: 2-[cyanomethyl-(4-nitronaphthalen-1-yl)amino]acetonitrile
• CAS: 1417737-75-7
• 化学式: C₁₄H₁₀N₄O₂
• 分子量: 266.259
• InChiKey: BDNPVNGTJNKONP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  20
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  96.6
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  potassium cyanide 、 聚合甲醛 、 1-氨基-4-硝基萘 在 硫酸 、 zinc(II) chloride 作用下， 以 溶剂黄146 为溶剂， 反应 3.0h， 以52%的产率得到2-[(4-Nitronaphthalen-1-yl)amino]acetonitrile
  参考文献：
  名称：

  Development of New Cathepsin B Inhibitors: Combining Bioisosteric Replacements and Structure-Based Design To Explore the Structure–Activity Relationships of Nitroxoline Derivatives

  摘要：

  Human cathepsin B has many house-keeping functions, such as protein turnover in lysosomes. However, dysregulation of its activity is associated with numerous diseases, including cancers. We present here the structure-based design and synthesis of new cathepsin B inhibitors using the cocrystal structure of 5-nitro-8-hydroxyquinoline in the cathepsin B active site. A focused library of over 50 compounds was prepared by modifying positions 5, 7, and 8 of the parent compound nitroxoline. The kinetic parameters and modes of inhibition were characterized, and the selectivities of the most promising inhibitors were determined. The best performing inhibitor 17 was effective in cell-based in vitro models of tumor invasion, where it significantly abrogated invasion of MCF-10A neoT cells. These data show that we have successfully explored the structure-activity relationships of nitroxoline derivatives to provide new inhibitors that could eventually lead to compounds with clinical usefulness against the deleterious effects of cathepsin B in cancer progression.

  DOI：

  10.1021/jm301544x

文献信息

• Development of New Cathepsin B Inhibitors: Combining Bioisosteric Replacements and Structure-Based Design To Explore the Structure–Activity Relationships of Nitroxoline Derivatives
  作者：Izidor Sosič、Bojana Mirković、Katharina Arenz、Bogdan Štefane、Janko Kos、Stanislav Gobec

  DOI：10.1021/jm301544x

  日期：2013.1.24

  Human cathepsin B has many house-keeping functions, such as protein turnover in lysosomes. However, dysregulation of its activity is associated with numerous diseases, including cancers. We present here the structure-based design and synthesis of new cathepsin B inhibitors using the cocrystal structure of 5-nitro-8-hydroxyquinoline in the cathepsin B active site. A focused library of over 50 compounds was prepared by modifying positions 5, 7, and 8 of the parent compound nitroxoline. The kinetic parameters and modes of inhibition were characterized, and the selectivities of the most promising inhibitors were determined. The best performing inhibitor 17 was effective in cell-based in vitro models of tumor invasion, where it significantly abrogated invasion of MCF-10A neoT cells. These data show that we have successfully explored the structure-activity relationships of nitroxoline derivatives to provide new inhibitors that could eventually lead to compounds with clinical usefulness against the deleterious effects of cathepsin B in cancer progression.