N-(2-(4-Benzylpiperazin-1-yl)-5-bromophenyl)-2-imino-2H-chromene-3-carboxamide | 1429200-03-2

• 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: N-(2-(4-Benzylpiperazin-1-yl)-5-bromophenyl)-2-imino-2H-chromene-3-carboxamide
• 英文别名: N-[2-(4-benzylpiperazin-1-yl)-5-bromophenyl]-2-iminochromene-3-carboxamide
• CAS: 1429200-03-2
• 化学式: C₂₇H₂₅BrN₄O₂
• 分子量: 517.425
• InChiKey: HSSQZTUBGOSCDN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.2
• 重原子数：
  34
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  68.7
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  N-(2-(4-Benzylpiperazin-1-yl)-5-bromophenyl)-2-imino-2H-chromene-3-carboxamide 、 苯胺 以 溶剂黄146 为溶剂， 以78%的产率得到N-(2-(4-benzylpiperazin-1-yl)-5-bromophenyl)-2-(phenylimino)-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：

  2,5-二溴硝基苯 在 哌啶 、 sodium dithionite 、 sodium carbonate 、 potassium carbonate 、 三乙胺 、 三氟乙酸 作用下， 以 甲醇 、 二氯甲烷 、 水 、 异丙醇 、 甲苯 为溶剂， 反应 43.25h， 生成 N-(2-(4-Benzylpiperazin-1-yl)-5-bromophenyl)-2-imino-2H-chromene-3-carboxamide
  参考文献：
  名称：

  作为潜在抗阿尔茨海默病药物的亚氨基-2H-铬烯衍生物：设计、合成、生物学评价和计算机研究

  摘要：

  合理设计和合成了一系列新的亚氨基-2 H-色烯衍生物作为抗阿尔茨海默病的新型多功能药物。一组苯基亚氨基-2 H-色烯以及新合成的亚氨基色烯衍生物被评估为 BACE1、乙酰胆碱酯酶 (AChE) 和丁酰胆碱酯酶 (BuChE) 抑制剂。结果表明，在亚氨基色素组中，带有氟苄基部分的10c是最有效的 BACE1 抑制剂，IC 50值为 6.31 μM。体外抗胆碱能活性表明，带有苄基侧基的化合物10a是 AChE（30 μM 时抑制百分比=24.4）和 BuChE（IC 50= 3.3 微米）。还进行了化合物10a针对 BuChE的动力学分析，并显示出混合型抑制模式。神经保护评估显示，化合物11b是一种具有羟乙基部分的苯基亚氨基-2 H-色烯衍生物，在 25 μM 时对 Aβ 诱导的 PC12 神经元细胞损伤提供 32.3% 的保护。此外，针对 BACE1 和 BuChE 的最有效化合物的对接和模拟研究证实了实验结果。

  DOI：

  10.1002/cbdv.202100599

文献信息

• Phenylimino-2 H -chromen-3-carboxamide derivatives as novel small molecule inhibitors of β-secretase (BACE1)
  作者：Najmeh Edraki、Omidreza Firuzi、Alireza Foroumadi、Ramin Miri、Armin Madadkar-Sobhani、Mehdi Khoshneviszadeh、Abbas Shafiee

  DOI：10.1016/j.bmc.2013.01.064

  日期：2013.4

  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.
• Imino‐2 <i>H</i> ‐Chromene Based Derivatives as Potential Anti‐Alzheimer's Agents: Design, Synthesis, Biological Evaluation and <i>in Silico</i> Study
  作者：Mahshid Attarroshan、Omidreza Firuzi、Aida Iraji、Shahrzad Sharifi、Marjan Tavakkoli、Mahmmod Vesal、Mahsima Khoshneviszadeh、Somayeh Pirhadi、Najmeh Edraki

  DOI：10.1002/cbdv.202100599

  日期：2022.1

  A new series of imino-2H-chromene derivatives were rationally designed and synthesized as novel multifunctional agents against Alzheimer's disease. A set of phenylimino-2H-chromenes as well as the newly synthesized iminochromene derivatives were evaluated as BACE1, acetylcholinesterase (AChE), and butyrylcholinesterase (BuChE) inhibitors. The results indicated that among the iminochromene set, 10c

  合理设计和合成了一系列新的亚氨基-2 H-色烯衍生物作为抗阿尔茨海默病的新型多功能药物。一组苯基亚氨基-2 H-色烯以及新合成的亚氨基色烯衍生物被评估为 BACE1、乙酰胆碱酯酶 (AChE) 和丁酰胆碱酯酶 (BuChE) 抑制剂。结果表明，在亚氨基色素组中，带有氟苄基部分的10c是最有效的 BACE1 抑制剂，IC 50值为 6.31 μM。体外抗胆碱能活性表明，带有苄基侧基的化合物10a是 AChE（30 μM 时抑制百分比=24.4）和 BuChE（IC 50= 3.3 微米）。还进行了化合物10a针对 BuChE的动力学分析，并显示出混合型抑制模式。神经保护评估显示，化合物11b是一种具有羟乙基部分的苯基亚氨基-2 H-色烯衍生物，在 25 μM 时对 Aβ 诱导的 PC12 神经元细胞损伤提供 32.3% 的保护。此外，针对 BACE1 和 BuChE 的最有效化合物的对接和模拟研究证实了实验结果。