2-chloro-1-(4-(3,4,5-trimethoxybenzyl)piperazin-1-yl)ethanone | 220832-41-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 2-chloro-1-(4-(3,4,5-trimethoxybenzyl)piperazin-1-yl)ethanone
• 英文别名: 2-Chloro-1-[4-[(3,4,5-trimethoxyphenyl)methyl]piperazin-1-yl]ethanone
• CAS: 220832-41-7
• 化学式: C₁₆H₂₃ClN₂O₄
• 分子量: 342.823
• InChiKey: VNVBVNFLEXJYRM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  23
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  51.2
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (3S)-1-benzylsulfonylpyrrolidin-3-amine 、 2-chloro-1-(4-(3,4,5-trimethoxybenzyl)piperazin-1-yl)ethanone 在 potassium iodide 作用下， 以 四氢呋喃 为溶剂， 反应 20.0h， 以48.2%的产率得到(S)-2-((1-(benzylsulfonyl)pyrrolidin-3-yl)amino)-1-(4-(3,4,5-trimethoxybenzyl)piperazin-1-yl)ethanone
  参考文献：
  名称：

  Exploration of (S)-3-aminopyrrolidine as a potentially interesting scaffold for discovery of novel Abl and PI3K dual inhibitors

  摘要：

  Based on the literature-reported compensatory effect of PI3K on Abl inhibition and the improved preclinical effect of drug combination of Abl and PI3K inhibitors, a series of compounds bearing novel scaffold of (S)-3-aminopyrrolidine was identified as Abl and PI3K dual inhibitors through support vector machine screening tool, which were subsequently synthesized and tested. Most compounds demonstrated promising cytoxicity against a CML leukemia cell-line K562 and moderate inhibition against Abl and PI3K kinases. These compounds induced no apoptosis in K562 cell-line, suggesting that their cytotoxic activities are unlikely duo to other known anti-CML mechanisms. Molecular docking study further showed that the compound 5k could bind with both Abl and PI3K, but the weaker binding with Abl compared to Imatinib is consistent with its low kinase inhibitory rates. These plus literature-reported evidences suggest that the promising cytotoxic effect of our novel compounds might be due to the collective effect of Abl and PI3K inhibition. (c) 2011 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2011.01.020
• 作为产物：
  描述：

  3,4,5-三甲氧基苄氯 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 4.0h， 生成 2-chloro-1-(4-(3,4,5-trimethoxybenzyl)piperazin-1-yl)ethanone
  参考文献：
  名称：

  Exploration of (S)-3-aminopyrrolidine as a potentially interesting scaffold for discovery of novel Abl and PI3K dual inhibitors

  摘要：

  Based on the literature-reported compensatory effect of PI3K on Abl inhibition and the improved preclinical effect of drug combination of Abl and PI3K inhibitors, a series of compounds bearing novel scaffold of (S)-3-aminopyrrolidine was identified as Abl and PI3K dual inhibitors through support vector machine screening tool, which were subsequently synthesized and tested. Most compounds demonstrated promising cytoxicity against a CML leukemia cell-line K562 and moderate inhibition against Abl and PI3K kinases. These compounds induced no apoptosis in K562 cell-line, suggesting that their cytotoxic activities are unlikely duo to other known anti-CML mechanisms. Molecular docking study further showed that the compound 5k could bind with both Abl and PI3K, but the weaker binding with Abl compared to Imatinib is consistent with its low kinase inhibitory rates. These plus literature-reported evidences suggest that the promising cytotoxic effect of our novel compounds might be due to the collective effect of Abl and PI3K inhibition. (c) 2011 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2011.01.020

文献信息

• Exploration of (S)-3-aminopyrrolidine as a potentially interesting scaffold for discovery of novel Abl and PI3K dual inhibitors
  作者：Cunlong Zhang、Chunyan Tan、Xuyu Zu、Xin Zhai、Feng Liu、Bizhu Chu、Xiaohua Ma、Yuzong Chen、Ping Gong、Yuyang Jiang

  DOI：10.1016/j.ejmech.2011.01.020

  日期：2011.4

  Based on the literature-reported compensatory effect of PI3K on Abl inhibition and the improved preclinical effect of drug combination of Abl and PI3K inhibitors, a series of compounds bearing novel scaffold of (S)-3-aminopyrrolidine was identified as Abl and PI3K dual inhibitors through support vector machine screening tool, which were subsequently synthesized and tested. Most compounds demonstrated promising cytoxicity against a CML leukemia cell-line K562 and moderate inhibition against Abl and PI3K kinases. These compounds induced no apoptosis in K562 cell-line, suggesting that their cytotoxic activities are unlikely duo to other known anti-CML mechanisms. Molecular docking study further showed that the compound 5k could bind with both Abl and PI3K, but the weaker binding with Abl compared to Imatinib is consistent with its low kinase inhibitory rates. These plus literature-reported evidences suggest that the promising cytotoxic effect of our novel compounds might be due to the collective effect of Abl and PI3K inhibition. (c) 2011 Elsevier Masson SAS. All rights reserved.