2,2-Dimethyl-N-(2-oxo-6-piperazin-1-yl-2H-chromen-3-yl)-propionamide | 752257-95-7

• 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: 2,2-Dimethyl-N-(2-oxo-6-piperazin-1-yl-2H-chromen-3-yl)-propionamide
• CAS: 752257-95-7
• 化学式: C₁₈H₂₃N₃O₃
• 分子量: 329.399
• InChiKey: NLAIJNBGZZOJLB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.19
• 重原子数：
  24.0
• 可旋转键数：
  2.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  74.58
• 氢给体数：
  2.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  3-(4-iodobutyl)-1H-indole-5-carbonitrile 、 2,2-Dimethyl-N-(2-oxo-6-piperazin-1-yl-2H-chromen-3-yl)-propionamide 在 N,N-二异丙基乙胺 、 盐酸 作用下， 以 N-甲基吡咯烷酮 、 异丙醇 为溶剂， 反应 48.0h， 以9%的产率得到N-(6-{4-[4-(5-cyano-1H-indol-3-yl)butyl]piperazin-1-yl}-2-oxo-2H-chromen-3-yl)-2,2-dimethylpropionamide hydrochloride
  参考文献：
  名称：

  Dual 5-HT1A agonists and 5-HT re-uptake inhibitors by combination of indole-butyl-amine and chromenonyl-piperazine structural elements in a single molecular entity

  摘要：

  The dual serotonin (5-HT) re-uptake inhibitor and 5-HT1A receptor agonist vilazodone was found to increase central serotonin levels in rat brain. In the course of structural modifications of vilazodone 3-{4-[4-(2-oxo-2H-1-benzopyran-6-yl)-1-piperazinyl]-butyl}-1H-indole-5-carbonitrile 8i and its fluorine analogue 6-{4-[4-(5-fluor-3-indolyl)-butyl]-1-piperazinyl}-2H-1-benzopyran-2-one have been identified. These unsubstituted chromenones are equally potent at the 5-HT1A receptor and 5-HT transporter. The implementation of nitrogen functionalities in position 3 of the chromenones resulted in compounds acting as agonists at the 5-HT1A receptor and as 5-HT re-uptake inhibitors like vilazodone. Ex vivo 5-HT re-uptake inhibition and in vitro 5-HT agonism were determined in the PCA- and GTRgammaS-assay, respectively. The potential of these chromenones to increase central 5-HT levels was measured in microdialysis studies and especially the derivatives 3-{4-[4-(3-amino-2-oxo-2H-chromen-6-yl)-piperazin-1-yl]-butyl-1H-indole-5-carbonitrile 8f, ethyl (6-{4-[4-(5-cyano-1H-indol-3-yl)-butyl]-piperazin-1-yl}-2-oxo-2H-chromen-3-yl)-carbamate 8h and N-(6-{4-[4-(5-cyano-1H-indol-3-yl)-butyl]-piperazin-1-yl}-2-oxo-2H-chromen-3-yl)-acetamide 8k give rise to rapid development of increased serotonin levels in rat brain cortex, lasting longer than 3h. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2004.07.014
• 作为产物：
  描述：

  4-(3-甲酰基-4-羟基苯基)哌嗪-1-羧酸叔丁酯 在 palladium on activated charcoal 哌啶 、 氢气 、 溶剂黄146 作用下， 以 乙醇 、 二氯甲烷 、 乙腈 为溶剂， 生成 2,2-Dimethyl-N-(2-oxo-6-piperazin-1-yl-2H-chromen-3-yl)-propionamide
  参考文献：
  名称：

  Dual 5-HT1A agonists and 5-HT re-uptake inhibitors by combination of indole-butyl-amine and chromenonyl-piperazine structural elements in a single molecular entity

  摘要：

  The dual serotonin (5-HT) re-uptake inhibitor and 5-HT1A receptor agonist vilazodone was found to increase central serotonin levels in rat brain. In the course of structural modifications of vilazodone 3-{4-[4-(2-oxo-2H-1-benzopyran-6-yl)-1-piperazinyl]-butyl}-1H-indole-5-carbonitrile 8i and its fluorine analogue 6-{4-[4-(5-fluor-3-indolyl)-butyl]-1-piperazinyl}-2H-1-benzopyran-2-one have been identified. These unsubstituted chromenones are equally potent at the 5-HT1A receptor and 5-HT transporter. The implementation of nitrogen functionalities in position 3 of the chromenones resulted in compounds acting as agonists at the 5-HT1A receptor and as 5-HT re-uptake inhibitors like vilazodone. Ex vivo 5-HT re-uptake inhibition and in vitro 5-HT agonism were determined in the PCA- and GTRgammaS-assay, respectively. The potential of these chromenones to increase central 5-HT levels was measured in microdialysis studies and especially the derivatives 3-{4-[4-(3-amino-2-oxo-2H-chromen-6-yl)-piperazin-1-yl]-butyl-1H-indole-5-carbonitrile 8f, ethyl (6-{4-[4-(5-cyano-1H-indol-3-yl)-butyl]-piperazin-1-yl}-2-oxo-2H-chromen-3-yl)-carbamate 8h and N-(6-{4-[4-(5-cyano-1H-indol-3-yl)-butyl]-piperazin-1-yl}-2-oxo-2H-chromen-3-yl)-acetamide 8k give rise to rapid development of increased serotonin levels in rat brain cortex, lasting longer than 3h. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2004.07.014