ethyl (3R)-t-butoxycarbonylamino-(3R)-(4-dimethylcarbamoyloxy-2-methoxymethoxy-phenyl)-propionate | 444646-80-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: ethyl (3R)-t-butoxycarbonylamino-(3R)-(4-dimethylcarbamoyloxy-2-methoxymethoxy-phenyl)-propionate
• 英文别名: ethyl (3R)-3-[4-(dimethylcarbamoyloxy)-2-(methoxymethoxy)phenyl]-3-[(2-methylpropan-2-yl)oxycarbonylamino]propanoate
• CAS: 444646-80-4
• 化学式: C₂₁H₃₂N₂O₈
• 分子量: 440.494
• InChiKey: NEODMAMFHKYWIX-MRXNPFEDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  31
• 可旋转键数：
  13
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  113
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  ethyl (3R)-t-butoxycarbonylamino-(3R)-(4-dimethylcarbamoyloxy-2-methoxymethoxy-phenyl)-propionate 在 吡啶 、 RuCl2(1,3-dimesityl-imidazolidin-2-yl)(PCy3)(=CHPh) 、 盐酸 、 lithium aluminium tetrahydride 、 四(三苯基膦)钯 、 2,6-二叔丁基苯酚 、 sodium hydride 、 三乙胺 、 三苯基膦 、 lithium chloride 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 、 二氯甲烷 、 乙酸乙酯 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 47.59h， 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：

  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：

  二甲氨基甲酰氯 、 3-tert-butoxycarbonylamino-3-(4-hydroxy-2-methoxymethoxyphenyl)propionic acid ethyl ester 在 potassium carbonate 作用下， 以 DMF (N,N-dimethyl-formamide) 为溶剂， 反应 3.0h， 以97%的产率得到ethyl (3R)-t-butoxycarbonylamino-(3R)-(4-dimethylcarbamoyloxy-2-methoxymethoxy-phenyl)-propionate
  参考文献：
  名称：

  BENZYLAMINE ANALOGUE

  摘要：

  公开号：

  EP1362844B1

文献信息

• Design and Synthesis of Dual Inhibitors of Acetylcholinesterase and Serotonin Transporter Targeting Potential Agents for Alzheimer's Disease
  作者：Hiroshi Kogen、Narihiro Toda、Keiko Tago、Shinji Marumoto、Kazuko Takami、Mayuko Ori、Naho Yamada、Kazuo Koyama、Shunji Naruto、Kazumi Abe、Reina Yamazaki、Takao Hara、Atsushi Aoyagi、Yasuyuki Abe、Tsugio Kaneko

  DOI：10.1021/ol026418e

  日期：2002.10.1

  [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.