2H-2-Benzazepine-2-carboxylic acid,7-[[(dimethylamino)carbonyl]oxy]-1,3,4,5-tetrahydro-5-methylene-1-[2-(4-nitrophenoxy)ethyl]-, 1,1-dimethylethyl ester | 649722-88-3

• 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: 2H-2-Benzazepine-2-carboxylic acid,7-[[(dimethylamino)carbonyl]oxy]-1,3,4,5-tetrahydro-5-methylene-1-[2-(4-nitrophenoxy)ethyl]-, 1,1-dimethylethyl ester
• 英文别名: 7-Dimethylcarbamoyloxy-5-methylene-1-[2-(4-nitro-phenoxy)-ethyl]-1,3,4,5-tetrahydro-benzo[c]azepine-2-carboxylic acid tert-butyl ester
• CAS: 649722-88-3
• 化学式: C₂₇H₃₃N₃O₇
• 分子量: 511.575
• InChiKey: ZFKNQXDDSDHPCM-UHFFFAOYSA-N

物化性质

• 沸点：
  650.2±55.0 °C(Predicted)
• 密度：
  1.25±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.82
• 重原子数：
  37.0
• 可旋转键数：
  6.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  111.45
• 氢给体数：
  0.0
• 氢受体数：
  7.0

反应信息

• 作为反应物：
  描述：

  2H-2-Benzazepine-2-carboxylic acid,7-[[(dimethylamino)carbonyl]oxy]-1,3,4,5-tetrahydro-5-methylene-1-[2-(4-nitrophenoxy)ethyl]-, 1,1-dimethylethyl ester 在 盐酸 、 甲酸 作用下， 以 水 、 乙酸乙酯 为溶剂， 反应 15.0h， 生成 dimethylcarbamic acid 2-methyl-5-methylene-1-[2-(4-nitrophenoxy)ethyl]-2,3,4,5-tetrahydro-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：

  甲基三苯基溴化膦 、 7-dimethylcarbamoyloxy-1-[2-(4-nitrophenoxy)ethyl]-5-oxo-1,3,4,5-tetrahydrobenzo[c]azepine-2-carboxylic acid tert-butyl ester 在 potassium tert-butylate 作用下， 以 四氢呋喃 、 苯 为溶剂， 反应 1.0h， 以24%的产率得到2H-2-Benzazepine-2-carboxylic acid,7-[[(dimethylamino)carbonyl]oxy]-1,3,4,5-tetrahydro-5-methylene-1-[2-(4-nitrophenoxy)ethyl]-, 1,1-dimethylethyl 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