2-carboxamide-3-amino-N-(1-benzylpiperidin-4-yl)quinoxaline | 1350648-15-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: 2-carboxamide-3-amino-N-(1-benzylpiperidin-4-yl)quinoxaline
• 英文别名: 3-amino-N-(1-benzylpiperidin-4-yl)quinoxaline-2-carboxamide
• CAS: 1350648-15-5
• 化学式: C₂₁H₂₃N₅O
• 分子量: 361.447
• InChiKey: KDKUGWOQDWQSRF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  27
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  84.1
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  4-氨基-1-苄基哌啶 、 3-氨基喹喔啉-2-羧酸 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 13.0h， 以73%的产率得到2-carboxamide-3-amino-N-(1-benzylpiperidin-4-yl)quinoxaline
  参考文献：
  名称：

  Searching for the Multi-Target-Directed Ligands against Alzheimer’s disease: Discovery of quinoxaline-based hybrid compounds with AChE, H3R and BACE 1 inhibitory activities

  摘要：

  A novel series of quinoxaline derivatives, as Multi-Target-Directed Ligands (MTDLs) for AD treatment, were designed by lending the core structural elements required for H3R antagonists and hybridizing BACE 1 inhibitor 1 with AChE inhibitor BYYT-25. A virtual database consisting of quinoxaline derivatives was first screened on a pharmacophore model of BACE 1 inhibitors, and then filtered by a molecular docking model of AChE. Seventeen quinoxaline derivatives with high score values were picked out, synthesized and evaluated for their biological activities. Compound 11a, the most effective MTDL, showed the potent activity to H3R/AChE/BACE 1 (H3R antagonism, IC50 = 280.0 +/- 98.0 nM; H3R inverse agonism, IC50 = 189.3 +/- 95.7 nM; AChE, IC50 = 483 +/- 5 nM; BACE 1, 46.64 +/- 2.55% inhibitory rate at 20 mu M) and high selectivity over H1R/H2R/H4R. Furthermore, the protein binding patterns between 11a and AChE/BACE 1 showed that it makes several essential interactions with the enzymes. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.09.061

文献信息

• Searching for the Multi-Target-Directed Ligands against Alzheimer’s disease: Discovery of quinoxaline-based hybrid compounds with AChE, H3R and BACE 1 inhibitory activities
  作者：Wenhai Huang、Li Tang、Ying Shi、Shufang Huang、Lei Xu、Rong Sheng、Peng Wu、Jia Li、Naiming Zhou、Yongzhou Hu

  DOI：10.1016/j.bmc.2011.09.061

  日期：2011.12

  A novel series of quinoxaline derivatives, as Multi-Target-Directed Ligands (MTDLs) for AD treatment, were designed by lending the core structural elements required for H3R antagonists and hybridizing BACE 1 inhibitor 1 with AChE inhibitor BYYT-25. A virtual database consisting of quinoxaline derivatives was first screened on a pharmacophore model of BACE 1 inhibitors, and then filtered by a molecular docking model of AChE. Seventeen quinoxaline derivatives with high score values were picked out, synthesized and evaluated for their biological activities. Compound 11a, the most effective MTDL, showed the potent activity to H3R/AChE/BACE 1 (H3R antagonism, IC50 = 280.0 +/- 98.0 nM; H3R inverse agonism, IC50 = 189.3 +/- 95.7 nM; AChE, IC50 = 483 +/- 5 nM; BACE 1, 46.64 +/- 2.55% inhibitory rate at 20 mu M) and high selectivity over H1R/H2R/H4R. Furthermore, the protein binding patterns between 11a and AChE/BACE 1 showed that it makes several essential interactions with the enzymes. (C) 2011 Elsevier Ltd. All rights reserved.