[(R)-1-(4-Dimethylcarbamoyloxy-2-methoxymethoxy-phenyl)-3-(4-nitro-phenoxy)-propyl]-carbamic acid tert-butyl ester | 474295-96-0

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 直链 1,3-二芳基丙烷
• 英文名称: [(R)-1-(4-Dimethylcarbamoyloxy-2-methoxymethoxy-phenyl)-3-(4-nitro-phenoxy)-propyl]-carbamic acid tert-butyl ester
• CAS: 474295-96-0
• 化学式: C₂₅H₃₃N₃O₉
• 分子量: 519.552
• InChiKey: IMGBYCCUUOAUFP-OAQYLSRUSA-N

物化性质

• 沸点：
  655.7±55.0 °C(Predicted)
• 密度：
  1.228±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.67
• 重原子数：
  37.0
• 可旋转键数：
  11.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  138.7
• 氢给体数：
  1.0
• 氢受体数：
  9.0

反应信息

• 作为反应物：
  描述：

  [(R)-1-(4-Dimethylcarbamoyloxy-2-methoxymethoxy-phenyl)-3-(4-nitro-phenoxy)-propyl]-carbamic acid tert-butyl ester 在 palladium diacetate 吡啶 、 盐酸 、 1,1'-双(二苯基膦)二茂铁 、 甲酸 、 sodium hydride 、 三乙胺 作用下， 以 甲醇 、 二氯甲烷 、 水 、 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， 反应 22.17h， 生成 dimethylcarbamic acid 4-[1-methylamino-3-(4-nitrophenoxy)propyl]phenyl ester hydrochloride salt
  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
• 作为产物：
  描述：

  3-tert-butoxycarbonylamino-3-(4-hydroxy-2-methoxymethoxyphenyl)propionic acid ethyl ester 在 lithium aluminium tetrahydride 、 potassium carbonate 、 三苯基膦 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 4.42h， 生成 [(R)-1-(4-Dimethylcarbamoyloxy-2-methoxymethoxy-phenyl)-3-(4-nitro-phenoxy)-propyl]-carbamic 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