2-((5-nitroquinolin-8-yl)oxy)acetonitrile | 88757-90-8

• 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: 2-((5-nitroquinolin-8-yl)oxy)acetonitrile
• 英文别名: 8-cyanomethoxy-5-nitroquinoline；[(5-Nitroquinolin-8-yl)oxy]acetonitrile；2-(5-nitroquinolin-8-yl)oxyacetonitrile
• CAS: 88757-90-8
• 化学式: C₁₁H₇N₃O₃
• 分子量: 229.195
• InChiKey: LGHNMMOCWYOKFR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  17
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  91.7
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-((5-nitroquinolin-8-yl)oxy)acetonitrile 在 盐酸 作用下， 以 乙醚 、 水 为溶剂， 反应 25.0h， 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
• 作为产物：
  描述：

  8-cyanomethoxyquinoline 在 硫酸 、 potassium nitrate 作用下， 反应 1.0h， 以85%的产率得到2-((5-nitroquinolin-8-yl)oxy)acetonitrile
  参考文献：
  名称：

  喹啉体系上的微波辅助亲核取代反应：硝基氧杂环丁烷氨基类似物的合成

  摘要：

  描述了一个可靠的协议，用于合成一系列药理学上令人关注的硝基氧杂环丁烷的5-氨基类似物（5-硝基-8-羟基喹啉）。O-氰基甲基化喹啉衍生物的氰基甲氧基被各种伯胺和仲胺空前取代，选择性地以中等至高收率提供了5-硝基喹啉-8-基胺。与常规加热相比，在微波条件下反应显着加速。

  DOI：

  10.1016/j.tetlet.2012.02.017

文献信息

• Synthesis and evaluation of a large library of nitroxoline derivatives as pancreatic cancer antiproliferative agents
  作者：Serena Veschi、Simone Carradori、Laura De Lellis、Rosalba Florio、Davide Brocco、Daniela Secci、Paolo Guglielmi、Mattia Spano、Anatoly P. Sobolev、Alessandro Cama

  DOI：10.1080/14756366.2020.1780228

  日期：2020.1.1

  compound. The new derivatives showed a valuable anti-proliferative effect and some displayed a greater effect as compared to nitroxoline against three pancreatic cancer cell lines with different genetic profiles. In particular, in silico pharmacokinetic data, clonogenicity assays and selectivity indexes of the most promising compounds showed several advantages for such derivatives, as compared to nitroxoline

  摘要 胰腺癌（PC）是最致命的癌症之一，在大多数情况下，被诊断为局部晚期或转移性疾病，当前的治疗选择非常不令人满意。基于旧的尿液抗菌剂硝恶啉显示的抗增殖作用，我们探索了一个新合成的大型文库，以阐明母体化合物的OH部分和吡啶环的重要性。新的衍生物显示出有价值的抗增殖作用，并且与硝基氧代林相比，对三种具有不同遗传特征的胰腺癌细胞系显示出更大的作用。特别是计算机与硝氧索林相比，最有前途的化合物的药代动力学数据，克隆形成性测定和选择性指数显示了此类衍生物的多项优势。而且，与厄洛替尼（一种批准用于PC治疗的靶向药物）相比，其中一些新型化合物对PC细胞的细胞活力和/或克隆形成能力具有更强的影响。
• 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.
• A microwave-assisted nucleophilic substitution reaction on a quinoline system: the synthesis of amino analogues of nitroxoline
  作者：Bogdan Štefane、Franc Požgan、Izidor Sosič、Stanislav Gobec

  DOI：10.1016/j.tetlet.2012.02.017

  日期：2012.4

  A reliable protocol for the synthesis of a series of 8-amino analogues of pharmacologically interesting nitroxoline (5-nitro-8-hydroxyquinoline) is described. The unprecedented displacement of the cyanomethoxy group of an O-cyanomethylated quinoline derivative by various primary and secondary amines selectively affords 5-nitroquinolin-8-ylamines in moderate-to-high yields. The reactions were accelerated

  描述了一个可靠的协议，用于合成一系列药理学上令人关注的硝基氧杂环丁烷的5-氨基类似物（5-硝基-8-羟基喹啉）。O-氰基甲基化喹啉衍生物的氰基甲氧基被各种伯胺和仲胺空前取代，选择性地以中等至高收率提供了5-硝基喹啉-8-基胺。与常规加热相比，在微波条件下反应显着加速。