2-[[(8-hydroxy-5-nitroquinolin-7-yl)methyl](methyl)amino]acetonitrile | 1417737-66-6

• 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-[[(8-hydroxy-5-nitroquinolin-7-yl)methyl](methyl)amino]acetonitrile
• 英文别名: 2-[[(8-Hydroxy-5-nitroquinolin-7-yl)methyl](methyl)amino]acetonitrile；2-[(8-hydroxy-5-nitroquinolin-7-yl)methyl-methylamino]acetonitrile
• CAS: 1417737-66-6
• 化学式: C₁₃H₁₂N₄O₃
• 分子量: 272.263
• InChiKey: DYZSFVHDXAZQPT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  20
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  106
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  [ruthenium(II)(η⁶-1-methyl-4-isopropyl-benzene)(chloride)(μ-chloride)]₂ 、 2-[[(8-hydroxy-5-nitroquinolin-7-yl)methyl](methyl)amino]acetonitrile 以 丙酮 为溶剂， 反应 2.0h， 以80%的产率得到
  参考文献：
  名称：

  通过抑制组织蛋白酶B活性，有机胸腺素硝基氧衍生物损害了肿瘤细胞的侵袭。

  摘要：

  溶酶体半胱氨酸肽酶组织蛋白酶B（catB）是重要的肿瘤促进因子，参与肿瘤的进展和转移，是开发新型抗肿瘤药物的相关靶标。在本研究中，我们合成了11种钌化合物，它们带有先前被鉴定为catB活性的强效选择性可逆抑制剂或其衍生物的临床药物硝氧嘧啶。我们证明有机钌化是一种获得catB内肽和外肽酶活性的高效和特异性抑制剂的可行策略，如使用酶动力学和微尺度热泳所显示的。此外，我们显示了在低非细胞毒性浓度下，基于catB抑制作用的新型金属药物在体外基于细胞的功能测定中显着损害了肿瘤进展的过程。一般来说，

  DOI：

  10.1021/acs.inorgchem.9b01882
• 作为产物：
  描述：

  聚合甲醛 、 5-硝基-8-羟基喹啉 、 甲胺基乙氰 以 吡啶 、 水 为溶剂， 以70%的产率得到2-[[(8-hydroxy-5-nitroquinolin-7-yl)methyl](methyl)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.
• Organoruthenated Nitroxoline Derivatives Impair Tumor Cell Invasion through Inhibition of Cathepsin B Activity
  作者：Ana Mitrović、Jakob Kljun、Izidor Sosič、Matija Uršič、Anton Meden、Stanislav Gobec、Janko Kos、Iztok Turel

  DOI：10.1021/acs.inorgchem.9b01882

  日期：2019.9.16

  cysteine peptidase cathepsin B (catB) is an important tumor-promoting factor involved in tumor progression and metastasis representing a relevant target for the development of new antitumor agents. In the present study, we synthesized 11 ruthenium compounds bearing either the clinical agent nitroxoline that was previously identified as potent selective reversible inhibitor of catB activity or its derivatives

  溶酶体半胱氨酸肽酶组织蛋白酶B（catB）是重要的肿瘤促进因子，参与肿瘤的进展和转移，是开发新型抗肿瘤药物的相关靶标。在本研究中，我们合成了11种钌化合物，它们带有先前被鉴定为catB活性的强效选择性可逆抑制剂或其衍生物的临床药物硝氧嘧啶。我们证明有机钌化是一种获得catB内肽和外肽酶活性的高效和特异性抑制剂的可行策略，如使用酶动力学和微尺度热泳所显示的。此外，我们显示了在低非细胞毒性浓度下，基于catB抑制作用的新型金属药物在体外基于细胞的功能测定中显着损害了肿瘤进展的过程。一般来说，