2-((2-((7-chloroquinolin-4-yl)amino)ethyl)(methyl)amino)ethan-1-ol | 1415338-54-3

• 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-((2-((7-chloroquinolin-4-yl)amino)ethyl)(methyl)amino)ethan-1-ol
• 英文别名: 2-[2-[(7-Chloro-4-quinolyl)amino]ethyl-methyl-amino]ethanol；2-[2-[(7-chloroquinolin-4-yl)amino]ethyl-methylamino]ethanol
• CAS: 1415338-54-3
• 化学式: C₁₄H₁₈ClN₃O
• 分子量: 279.769
• InChiKey: ZRPRLDFNDYYSQJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  19
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  48.4
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-((2-((7-chloroquinolin-4-yl)amino)ethyl)(methyl)amino)ethan-1-ol 在 氯化亚砜 、 copper(II) sulfate 、 sodium ascorbate 、 sodium iodide 作用下， 以 水 、 N,N-二甲基甲酰胺 、 丙酮 、 甲苯 为溶剂， 反应 36.0h， 生成 N¹-((1-(tert-butyl)-1H-1,2,3-triazol-4-yl)methyl)-N²-(2-((7-chloroquinolin-4-yl)amino)ethyl)-N²-methylethane-1,2-diamine
  参考文献：
  名称：

  Discovery of Autophagy Inhibitors with Antiproliferative Activity in Lung and Pancreatic Cancer Cells

  摘要：

  The autophagy inhibitors chloroquine (CQ) and hydroxychloroquine (HCQ) have single agent antiproliferative activity against human cancer cell lines; however, low potency may limit their antitumor efficacy clinically. We synthesized a series of chloroquine analogs that retained the 4-aminoquinoline subunit and incorporated different substituted triazoles into the target structure. These compounds were tested for growth inhibition against H460 and HCC827 human lung cancer and BxPC3 pancreatic cancer cells. The most potent compound, EAD1, had an IC50 of 5.8 μM in the BxPC3 cells and was approximately 8-fold more potent than CQ and HCQ. EAD1 inhibited autophagy, as judged by the cellular accumulation of the autophagy-related autophagosome proteins LC3-II and p62 and induced apoptosis. The increases in LC3-II levels by the analogues were highly correlated with their growth inhibitory IC50s, suggesting that autophagy blockade is closely linked to inhibition of cell proliferation. EAD1 is a viable lead compound for evaluation of the antitumor activity of autophagy inhibitors in vivo.

  DOI：

  10.1021/ml500348p
• 作为产物：
  描述：

  2-(7-氯喹啉-4-氨基)乙醇 在 三乙胺 作用下， 以 四氢呋喃 为溶剂， 反应 0.75h， 生成 2-((2-((7-chloroquinolin-4-yl)amino)ethyl)(methyl)amino)ethan-1-ol
  参考文献：
  名称：

  新型硝基咪唑和硝基咪唑并恶嗪衍生物的合成及抗疟原虫和抗分枝杆菌评价

  摘要：

  描述了两个新系列的硝基咪唑和硝基咪唑并恶嗪衍生物的合成和抗疟原虫和抗分枝杆菌的评价。这些化合物中的大多数，尤其是杂交体9d、9f和14b，对恶性疟原虫的氯喹抗性 K1 菌株表现出有效的活性。此外，来自四唑系列的显着数字对结核分枝杆菌的活性明显高于标准结核病药物卡那霉素。

  DOI：

  10.1021/ml300362a

文献信息

• [EN] CHLOROQUINOLINE TRIAZOLE COMPOUNDS, COMPOSITION AND USES<br/>[FR] COMPOSÉS TRIAZOLE DE CHLOROQUINOLINE, COMPOSITION ET UTILISATIONS
  申请人：EINSTEIN COLL MED

  公开号：WO2016111957A1

  公开（公告）日：2016-07-14

  Chloroquinoline triazole compounds are provided, as are compositions comprising the compounds, and methods relating to them, including methods of inhibiting autophagy in biological systems and treatment of diseases, disorders or conditions in which autophagy inhibition can provide benefit, including treatment of cancer, rheumatoid arthritis, malaria, antiphospholipid antibody syndrome, lupus, chronic urticaria and Sjogren's disease.

  本发明提供了氯喹啉三唑化合物，以及包含该化合物的组合物和与其相关的方法，包括在生物系统中抑制自噬的方法和治疗疾病、紊乱或条件的方法，其中自噬抑制可以提供益处，包括治疗癌症、类风湿性关节炎、疟疾、抗磷脂抗体综合征、红斑狼疮、慢性荨麻疹和干燥综合征。
• Discovery of Autophagy Inhibitors with Antiproliferative Activity in Lung and Pancreatic Cancer Cells
  作者：Lars Ulrik Nordstrøm、Juan Sironi、Evelyn Aranda、Jorge Maisonet、Roman Perez-Soler、Peng Wu、Edward L. Schwartz

  DOI：10.1021/ml500348p

  日期：2015.2.12

  The autophagy inhibitors chloroquine (CQ) and hydroxychloroquine (HCQ) have single agent antiproliferative activity against human cancer cell lines; however, low potency may limit their antitumor efficacy clinically. We synthesized a series of chloroquine analogs that retained the 4-aminoquinoline subunit and incorporated different substituted triazoles into the target structure. These compounds were tested for growth inhibition against H460 and HCC827 human lung cancer and BxPC3 pancreatic cancer cells. The most potent compound, EAD1, had an IC50 of 5.8 μM in the BxPC3 cells and was approximately 8-fold more potent than CQ and HCQ. EAD1 inhibited autophagy, as judged by the cellular accumulation of the autophagy-related autophagosome proteins LC3-II and p62 and induced apoptosis. The increases in LC3-II levels by the analogues were highly correlated with their growth inhibitory IC50s, suggesting that autophagy blockade is closely linked to inhibition of cell proliferation. EAD1 is a viable lead compound for evaluation of the antitumor activity of autophagy inhibitors in vivo.
• Synthesis and Antiplasmodial and Antimycobacterial Evaluation of New Nitroimidazole and Nitroimidazooxazine Derivatives
  作者：Matshawandile Tukulula、Rajni-Kant Sharma、Maïa Meurillon、Aman Mahajan、Krupa Naran、Digby Warner、Jianxing Huang、Belew Mekonnen、Kelly Chibale

  DOI：10.1021/ml300362a

  日期：2013.1.10

  The synthesis and antiplasmodial and antimycobacterial evaluation of two new series of nitroimidazole and nitroimidazooxazine derivatives is described. The majority of these compounds, especially hybrids 9d, 9f, and 14b, exhibited potent activity against the chloroquine-resistant K1 strain of Plasmodium falciparum. Furthermore, a notable number from the tetrazole series were significantly more active

  描述了两个新系列的硝基咪唑和硝基咪唑并恶嗪衍生物的合成和抗疟原虫和抗分枝杆菌的评价。这些化合物中的大多数，尤其是杂交体9d、9f和14b，对恶性疟原虫的氯喹抗性 K1 菌株表现出有效的活性。此外，来自四唑系列的显着数字对结核分枝杆菌的活性明显高于标准结核病药物卡那霉素。