7-Dimethylcarbamoyloxy-1-[2-(4-nitro-phenoxy)-ethyl]-5-thiophen-2-yl-1,3-dihydro-benzo[c]azepine-2-carboxylic acid tert-butyl ester | 649722-98-5

• 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: 7-Dimethylcarbamoyloxy-1-[2-(4-nitro-phenoxy)-ethyl]-5-thiophen-2-yl-1,3-dihydro-benzo[c]azepine-2-carboxylic acid tert-butyl ester
• CAS: 649722-98-5
• 化学式: C₃₀H₃₃N₃O₇S
• 分子量: 579.674
• InChiKey: AFNUEHZUAWIOIA-UHFFFAOYSA-N

物化性质

• 沸点：
  716.2±60.0 °C(Predicted)
• 密度：
  1.270±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  6.91
• 重原子数：
  41.0
• 可旋转键数：
  7.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  111.45
• 氢给体数：
  0.0
• 氢受体数：
  8.0

反应信息

• 作为反应物：
  描述：

  7-Dimethylcarbamoyloxy-1-[2-(4-nitro-phenoxy)-ethyl]-5-thiophen-2-yl-1,3-dihydro-benzo[c]azepine-2-carboxylic acid tert-butyl 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-1-[2-(4-nitrophenoxy)ethyl]-5-(thiophen-2-yl)-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：

  5-dimethylcarbamoyloxy-2-formyl-phenyl trifluoromethanesulfonate 在 RuCl2(1,3-dimesityl-imidazolidin-2-yl)(PCy3)(=CHPh) 、 4-二甲氨基吡啶 、 potassium phosphate 、 锂硼氢 、 四(三苯基膦)钯 、 四溴化碳 、 2,6-二叔丁基苯酚 、 硼烷 、 四丁基氟化铵 、 三乙胺 、 三苯基膦 、 lithium chloride 、 lithium hexamethyldisilazane 、 lithium diisopropyl amide 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 正己烷 、 二氯甲烷 、 甲苯 、 乙腈 为溶剂， 反应 62.33h， 生成 7-Dimethylcarbamoyloxy-1-[2-(4-nitro-phenoxy)-ethyl]-5-thiophen-2-yl-1,3-dihydro-benzo[c]azepine-2-carboxylic acid tert-butyl 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