2-(2-methoxy-benzylamino)-N-{2-[2-(2-methoxy-benzylamino)-acetylamino]-ethyl}acetamide | 664339-42-8

• 英文名称: 2-(2-methoxy-benzylamino)-N-{2-[2-(2-methoxy-benzylamino)-acetylamino]-ethyl}acetamide
• CAS: 664339-42-8
• 化学式: C₂₆H₃₈N₄O₄
• 分子量: 470.612
• InChiKey: SLDFZNWTFHYHQZ-UHFFFAOYSA-N

物化性质

• 沸点：
  655.5±55.0 °C(Predicted)
• 密度：
  1.114±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.28
• 重原子数：
  34.0
• 可旋转键数：
  15.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  83.14
• 氢给体数：
  2.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  2-(2-methoxy-benzylamino)-N-{2-[2-(2-methoxy-benzylamino)-acetylamino]-ethyl}acetamide 在 dimethyl sulfide borane 作用下， 以 甲醇 、 二乙二醇二甲醚 为溶剂， 反应 85.0h， 生成 2,2,2-trifluoro-N-[2-(2-methoxy-benzylamino)ethyl]-N-(2-{[2-(2-methoxy-benzylamino)-ethyl]trifluoroacetyl-amino}-ethyl)-acetamide
  参考文献：
  名称：

  Design, synthesis and biological evaluation of ambenonium derivatives as AChE inhibitors

  摘要：

  Ambenonium (1), an old AChE inhibitor, is endowed with an outstanding affinity and a peculiar mechanism of action that, taken together, make it a very promising pharmacological tool for the treatment of Alzheimer's disease (AD). Unfortunately, the bisquaternary structure of 1 prevents its passage through the blood brain barrier. In a search of centrally active ambenonium derivatives, we planned to synthesize tertiary amines of 1, such as 2 and 3. In addition, to add new insights into the binding mechanism of the inhibitor, we designed constrained analogues of ambenonium by incorporating the diamine functions into cyclic moieties (4-12). The biological evaluation of the new compounds has been assessed in vitro against human AChE and BChE. All tertiary amine derivatives resulted more than 1000-fold less potent than 1 and, unlike prototype, did not show any selectivity between the two enzymes. This result, because of recent findings concerning the role of BChE in AD, makes our compounds, endowed with a well-balanced profile of AChE/BChE inhibition, valuable candidates for further development. To better clarify the interactions that account for the high affinity of 1, docking simulations and molecular dynamics studies on the AChE-1 complex were also carried out.

  DOI：

  10.1016/s0014-827x(03)00150-2
• 作为产物：
  描述：

  (2-methoxy-benzylamino)-acetic acid 在 三乙胺 作用下， 以 1,4-二氧六环 、 甲苯 为溶剂， 反应 48.25h， 生成 2-(2-methoxy-benzylamino)-N-{2-[2-(2-methoxy-benzylamino)-acetylamino]-ethyl}acetamide
  参考文献：
  名称：

  Design, synthesis and biological evaluation of ambenonium derivatives as AChE inhibitors

  摘要：

  Ambenonium (1), an old AChE inhibitor, is endowed with an outstanding affinity and a peculiar mechanism of action that, taken together, make it a very promising pharmacological tool for the treatment of Alzheimer's disease (AD). Unfortunately, the bisquaternary structure of 1 prevents its passage through the blood brain barrier. In a search of centrally active ambenonium derivatives, we planned to synthesize tertiary amines of 1, such as 2 and 3. In addition, to add new insights into the binding mechanism of the inhibitor, we designed constrained analogues of ambenonium by incorporating the diamine functions into cyclic moieties (4-12). The biological evaluation of the new compounds has been assessed in vitro against human AChE and BChE. All tertiary amine derivatives resulted more than 1000-fold less potent than 1 and, unlike prototype, did not show any selectivity between the two enzymes. This result, because of recent findings concerning the role of BChE in AD, makes our compounds, endowed with a well-balanced profile of AChE/BChE inhibition, valuable candidates for further development. To better clarify the interactions that account for the high affinity of 1, docking simulations and molecular dynamics studies on the AChE-1 complex were also carried out.

  DOI：

  10.1016/s0014-827x(03)00150-2