N-(2-(4-benzylpiperazin-1-yl)-5-bromophenyl)-2-cyanoacetamide | 1429199-99-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: N-(2-(4-benzylpiperazin-1-yl)-5-bromophenyl)-2-cyanoacetamide
• CAS: 1429199-99-4
• 化学式: C₂₀H₂₁BrN₄O
• 分子量: 413.317
• InChiKey: TXPHRADKXXFVMM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.62
• 重原子数：
  26.0
• 可旋转键数：
  5.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  59.37
• 氢给体数：
  1.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  N-(2-(4-benzylpiperazin-1-yl)-5-bromophenyl)-2-cyanoacetamide 、 水杨醛 在 哌啶 作用下， 以 甲醇 为溶剂， 反应 7.0h， 以87%的产率得到N-(2-(4-Benzylpiperazin-1-yl)-5-bromophenyl)-2-imino-2H-chromene-3-carboxamide
  参考文献：
  名称：

  Phenylimino-2 H -chromen-3-carboxamide derivatives as novel small molecule inhibitors of β-secretase (BACE1)

  摘要：

  The inhibition of beta secretase (BACE1) is potentially important approach to treatment of Alzheimer disease (AD). A novel series of 4-bromophenyl piperazine derivatives coupled to the phenylimino-2H-chromen-3-carboxamide scaffold were investigated as BACE1 inhibitors in this study. Docking study suggested that the phenyl-imino group of the scaffold establishes favorable p-p stacking interaction with side chain of Phe108 of flap pocket. Some of the docking proposed derivatives were synthesized and evaluated for BACE1 inhibitory activity using a FRET-based assay. High BACE1 inhibitory activities were observed from derivatives containing fused heteroaromtic groups attached through the aliphatic linkage to the N4-piperazine moiety, which may be attributed to the engagement of effective interactions with S1-S'1 sub-pocket residues. Of the most potent compounds, 9e displayed an IC50 value for BACE1 of 98 nM. Some of these derivatives demonstrated good inhibitory activity on A beta production in N2a-APPswe cells at 5 and 10 mu M. These compounds might be considered as promising BACE1 inhibitory agents that could lower A beta production in AD. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.01.064
• 作为产物：
  描述：

  3-硝基-4-(4-苄基-1-哌嗪)溴苯 在 sodium dithionate 、 sodium carbonate 作用下， 以 甲醇 、 水 、 甲苯 为溶剂， 生成 N-(2-(4-benzylpiperazin-1-yl)-5-bromophenyl)-2-cyanoacetamide
  参考文献：
  名称：

  Phenylimino-2 H -chromen-3-carboxamide derivatives as novel small molecule inhibitors of β-secretase (BACE1)

  摘要：

  The inhibition of beta secretase (BACE1) is potentially important approach to treatment of Alzheimer disease (AD). A novel series of 4-bromophenyl piperazine derivatives coupled to the phenylimino-2H-chromen-3-carboxamide scaffold were investigated as BACE1 inhibitors in this study. Docking study suggested that the phenyl-imino group of the scaffold establishes favorable p-p stacking interaction with side chain of Phe108 of flap pocket. Some of the docking proposed derivatives were synthesized and evaluated for BACE1 inhibitory activity using a FRET-based assay. High BACE1 inhibitory activities were observed from derivatives containing fused heteroaromtic groups attached through the aliphatic linkage to the N4-piperazine moiety, which may be attributed to the engagement of effective interactions with S1-S'1 sub-pocket residues. Of the most potent compounds, 9e displayed an IC50 value for BACE1 of 98 nM. Some of these derivatives demonstrated good inhibitory activity on A beta production in N2a-APPswe cells at 5 and 10 mu M. These compounds might be considered as promising BACE1 inhibitory agents that could lower A beta production in AD. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.01.064