N-(2-(1H-indol-2-yl)-4-oxo-3,4-dihydroquinazolin-6-yl)-3-(piperidin-1-yl)propanamide | 1428628-57-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: N-(2-(1H-indol-2-yl)-4-oxo-3,4-dihydroquinazolin-6-yl)-3-(piperidin-1-yl)propanamide
• 英文别名: N-[2-(1H-indol-2-yl)-4-oxo-3H-quinazolin-6-yl]-3-piperidin-1-ylpropanamide
• CAS: 1428628-57-2
• 化学式: C₂₄H₂₅N₅O₂
• 分子量: 415.495
• InChiKey: JOCZIAQMXYHQML-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  31
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  89.6
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  2-氨基-5-硝基苯酰胺 在 palladium 10% on activated carbon 、 氢气 、 溴 、 sodium acetate 、 potassium carbonate 、 溶剂黄146 、 sodium iodide 作用下， 以 甲醇 、 乙醇 、 二氯甲烷 为溶剂， 反应 24.5h， 生成 N-(2-(1H-indol-2-yl)-4-oxo-3,4-dihydroquinazolin-6-yl)-3-(piperidin-1-yl)propanamide
  参考文献：
  名称：

  2-(2-indolyl-)-4(3H)-quinazolines derivates as new inhibitors of AChE: design, synthesis, biological evaluation and molecular modelling

  摘要：

  We recently reported that synthetic derivatives of rutaecarpine alkaloid exhibited high acetyl cholinesterase (AChE) inhibitory activity and high selectivity for AChE over butyrylcholinesterases (BuChE). To explore novel effective drugs for the treatment of Alzheimer's disease (AD), in this paper, further research results were presented. Starting from a structure-based drug design, a series of novel 2-(2-indolyl-)-4(3H)-quinazolines derivates were designed and synthesized as the ring-opened analogues of rutaecarpine alkaloid and subjected to pharmacological evaluation as AChE inhibitors. Among them, derivates 3a-c and 3g-h exhibited strong inhibitory activity for AChE and high selectivity for AChE over BuChE. The structure-activity relationships were discussed and their binding conformation and simultaneous interactions mode were further clarified by kinetic characterization and the molecular docking studies.

  DOI：

  10.3109/14756366.2012.663363

文献信息

• 2-(2-indolyl-)-4(3<i>H</i>)-quinazolines derivates as new inhibitors of AChE: design, synthesis, biological evaluation and molecular modelling
  作者：Zeng Li、Bin Wang、Jin-Qiang Hou、Shi-Liang Huang、Tian-Miao Ou、Jia-Heng Tan、Lin-Kun An、Ding Li、Lian-Quan Gu、Zhi-Shu Huang

  DOI：10.3109/14756366.2012.663363

  日期：2013.6.1

  We recently reported that synthetic derivatives of rutaecarpine alkaloid exhibited high acetyl cholinesterase (AChE) inhibitory activity and high selectivity for AChE over butyrylcholinesterases (BuChE). To explore novel effective drugs for the treatment of Alzheimer's disease (AD), in this paper, further research results were presented. Starting from a structure-based drug design, a series of novel 2-(2-indolyl-)-4(3H)-quinazolines derivates were designed and synthesized as the ring-opened analogues of rutaecarpine alkaloid and subjected to pharmacological evaluation as AChE inhibitors. Among them, derivates 3a-c and 3g-h exhibited strong inhibitory activity for AChE and high selectivity for AChE over BuChE. The structure-activity relationships were discussed and their binding conformation and simultaneous interactions mode were further clarified by kinetic characterization and the molecular docking studies.