[(1R)-1-[2-(4-nitrophenoxy)ethyl]-2,3-dihydro-1H-2-benzazepin-7-yl] N,N-dimethylcarbamate | 474296-01-0

• 分子结构分类: 有机化合物 - 有机杂环化合物
• 英文名称: [(1R)-1-[2-(4-nitrophenoxy)ethyl]-2,3-dihydro-1H-2-benzazepin-7-yl] N,N-dimethylcarbamate
• CAS: 474296-01-0
• 化学式: C₂₁H₂₃N₃O₅
• 分子量: 397.431
• InChiKey: KZCOGBATRAHHLS-HXUWFJFHSA-N

物化性质

• 沸点：
  588.5±50.0 °C(Predicted)
• 密度：
  1.232±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  29
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  96.6
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  聚合甲醛 、 [(1R)-1-[2-(4-nitrophenoxy)ethyl]-2,3-dihydro-1H-2-benzazepin-7-yl] N,N-dimethylcarbamate 在 甲酸 作用下， 以 水 为溶剂， 反应 3.0h， 以78%的产率得到dimethylcarbamic acid (R)-2-methyl-1-[2-(4-nitrophenoxy)ethyl]-2,3-dihydro-1H-benzo[c]azepin-7-yl ester
  参考文献：
  名称：

  A conformational restriction approach to the development of dual inhibitors of acetylcholinesterase and serotonin transporter as potential agents for Alzheimer's disease

  摘要：

  Alzheimer's disease (AD) has been treated with acetylcholinesterase (AChE) inhibitors such as donepezil. However, the clinical usefulness of AChE inhibitors is limited mainly due to their adverse peripheral effects. Depression seen in AD patients has been treated with serotonin transporter (SERT) inhibitors. We considered that combining SERT and AChE inhibition could improve the clinical usefulness of AChE inhibitors. In a previous paper, we found a potential dual inhibitor, 1, of AChE (IC50 = 101 nM) and SERT (IC50 = 42 nM), but its AChE inhibition activity was less than donepezil (IC50 = 10 nM). Here, we report the conformationally restricted (R)-18a considerably enhanced inhibitory activity against AChE (IC50 14 nM) and SERT (IC50 = 6 nM). (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(03)00452-8
• 作为产物：
  描述：

  [(R)-1-(4-Dimethylcarbamoyloxy-2-methoxymethoxy-phenyl)-3-(4-nitro-phenoxy)-propyl]-carbamic acid tert-butyl ester 在 吡啶 、 RuCl2(1,3-dimesityl-imidazolidin-2-yl)(PCy3)(=CHPh) 、 盐酸 、 四(三苯基膦)钯 、 2,6-二叔丁基苯酚 、 sodium hydride 、 三乙胺 、 lithium chloride 作用下， 以 1,4-二氧六环 、 甲醇 、 二氯甲烷 、 水 、 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， 反应 46.17h， 生成 [(1R)-1-[2-(4-nitrophenoxy)ethyl]-2,3-dihydro-1H-2-benzazepin-7-yl] N,N-dimethylcarbamate
  参考文献：
  名称：

  Design and Synthesis of Dual Inhibitors of Acetylcholinesterase and Serotonin Transporter Targeting Potential Agents for Alzheimer's Disease

  摘要：

  [GRAPHICS]Highly efficient acetylcholinesterase (AChE) and serotonin transporter (SERT) dual inhibitors, (S)-4 and (R)-13 were designed and synthesized on the basis of the hypothetical model of AChE active site. Both compounds showed potent inhibitory activities against AChE and SERT.

  DOI：

  10.1021/ol026418e