2-(4-(((2-((2-((7-chloroquinolin-4-yl)amino)ethyl)(methyl)amino)ethyl)amino)methyl)-1H-1,2,3-triazol-1-yl)propan-1-ol

• 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-(4-(((2-((2-((7-chloroquinolin-4-yl)amino)ethyl)(methyl)amino)ethyl)amino)methyl)-1H-1,2,3-triazol-1-yl)propan-1-ol
• 英文别名: 3-[4-[[2-[2-[(7-Chloroquinolin-4-yl)amino]ethyl-methylamino]ethylamino]methyl]triazol-1-yl]propan-1-ol；3-[4-[[2-[2-[(7-chloroquinolin-4-yl)amino]ethyl-methylamino]ethylamino]methyl]triazol-1-yl]propan-1-ol
• 化学式: C₂₀H₂₈ClN₇O
• 分子量: 417.942
• InChiKey: BDQKBRWJGALEGT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  29
• 可旋转键数：
  12
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  91.1
• 氢给体数：
  3
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  2-(4-(((2-((2-((7-chloroquinolin-4-yl)amino)ethyl)(methyl)amino)ethyl)amino)methyl)-1H-1,2,3-triazol-1-yl)propan-1-ol 在 盐酸 作用下， 以 乙醚 为溶剂， 生成 2-(4-(((2-((2-((7-chloroquinolin-4-yl)amino)ethyl)(methyl)amino)ethyl)amino)methyl)-1H-1,2,3-triazol-1-yl)propan-1-ol hydrochloride
  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：

  N¹-(2-chloroethyl)-N²-(7-chloroquinolin-4-yl)-N¹-methylethane-1,2-diamine 在 copper(II) sulfate 、 sodium ascorbate 、 sodium iodide 作用下， 以 水 、 N,N-二甲基甲酰胺 、 丙酮 为溶剂， 反应 18.0h， 生成 2-(4-(((2-((2-((7-chloroquinolin-4-yl)amino)ethyl)(methyl)amino)ethyl)amino)methyl)-1H-1,2,3-triazol-1-yl)propan-1-ol
  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

文献信息

• 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.