Methyl 2-(5-nitroquinolin-8-yl)oxyacetate | 1179083-04-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: Methyl 2-(5-nitroquinolin-8-yl)oxyacetate
• CAS: 1179083-04-5
• 化学式: C₁₂H₁₀N₂O₅
• 分子量: 262.222
• InChiKey: ULKIWJNRMUNWHD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  19
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  94.2
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  8-cyanomethoxyquinoline 在 盐酸 、 硫酸 、 potassium nitrate 作用下， 以 乙醚 、 水 为溶剂， 反应 26.25h， 生成 Methyl 2-(5-nitroquinolin-8-yl)oxyacetate
  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

• [EN] NITROXOLINE PRODRUG AND USE THEREOF<br/>[FR] PROMÉDICAMENT DE NITROXOLINE ET UTILISATION ASSOCIÉE<br/>[ZH] 硝羟喹啉前药及其用途
  申请人：JIANGSU YAHONG MEDITECH CO LTD

  公开号：WO2020063824A1

  公开（公告）日：2020-04-02

  提供硝羟喹啉前药及其用途，具体地，提供式（I）化合物或其药学上可接受的盐、其制备方法、包含其的组合物、及其在制备用于抗感染和抗肿瘤药物中的用途，式（I）中各个基团的定义如说明书中所述。式（I）化合物相对于硝羟喹啉有更好的水溶性、血药浓度或半衰期等药代动力学参数。式（I）化合物可减少给药次数，同时具有在尿路领域以外的其他领域中应用的可能性。
• 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.