N-[2-(4-benzyloxy-phenyl)-1-(7-hydroxy-heptylcarbamoyl)-ethyl]-butyramide | 937377-31-6

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: N-[2-(4-benzyloxy-phenyl)-1-(7-hydroxy-heptylcarbamoyl)-ethyl]-butyramide
• CAS: 937377-31-6
• 化学式: C₂₇H₃₈N₂O₄
• 分子量: 454.61
• InChiKey: BWJIJACVJSASOT-VWLOTQADSA-N

物化性质

• 沸点：
  722.2±60.0 °C(Predicted)
• 密度：
  1.095±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.15
• 重原子数：
  33.0
• 可旋转键数：
  16.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  87.66
• 氢给体数：
  3.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  N-[2-(4-benzyloxy-phenyl)-1-(7-hydroxy-heptylcarbamoyl)-ethyl]-butyramide 在 palladium dihydroxide 盐酸 、 氢气 、 N,N-二异丙基乙胺 作用下， 以 甲醇 、 二氯甲烷 、 乙腈 为溶剂， 20.0~35.0 ℃ 、101.33 kPa 条件下， 反应 71.0h， 生成 N-[1-[7-(4-amino-butylamino)-heptylcarbamoyl]-2-(4-hydroxy-phenyl)-ethyl]-butyramide dihydrochloride
  参考文献：
  名称：

  A Subtype-Selective, Use-Dependent Inhibitor of Native AMPA Receptors

  摘要：

  AMPA (alpha-amino-3-hydroxy-5-methyl-4-isooxazole) receptors (AMPARs) are glutamate-gated ion channels that play central roles in the mammalian brain, mediating fast excitatory synaptic transmission and underlying several forms of synaptic plasticity. Two subtypes of AMPARs are primarily coexpressed at excitatory synapses in adult animals (GluR1/2 and GluR2/3 receptors). Efforts to distinguish between the potentially distinct roles these receptor subtypes play at synapses have been hampered by the absence of a subtype-selective AMPAR antagonist. Here we show that the polyamine philanthotoxin-7,4 (PhTx-74) is a subtype-selective AMPAR antagonist, inhibiting GluR1/2, but not GluR2/3 receptors, use-dependently. The molecular basis for the observed selectivity and a highly efficient synthesis of this remarkable toxin are also presented. PhTx-74 provides the first a means of directly monitoring subtype-specific changes in the composition of AMPARs at native synapses, including during hippocampal long-term potentiation (LTP), a form of synaptic plasticity thought to share processes related to learning and memory.

  DOI：

  10.1021/ja0705801
• 作为产物：
  描述：

  3-(4-benzyloxy-phenyl)-2-butyrylamino-propionic acid methyl ester 在 lithium hydroxide 、 N,N'-二环己基碳二亚胺 作用下， 以 四氢呋喃 、 二氯甲烷 、 乙酸乙酯 为溶剂， 反应 36.0h， 生成 N-[2-(4-benzyloxy-phenyl)-1-(7-hydroxy-heptylcarbamoyl)-ethyl]-butyramide
  参考文献：
  名称：

  A Subtype-Selective, Use-Dependent Inhibitor of Native AMPA Receptors

  摘要：

  AMPA (alpha-amino-3-hydroxy-5-methyl-4-isooxazole) receptors (AMPARs) are glutamate-gated ion channels that play central roles in the mammalian brain, mediating fast excitatory synaptic transmission and underlying several forms of synaptic plasticity. Two subtypes of AMPARs are primarily coexpressed at excitatory synapses in adult animals (GluR1/2 and GluR2/3 receptors). Efforts to distinguish between the potentially distinct roles these receptor subtypes play at synapses have been hampered by the absence of a subtype-selective AMPAR antagonist. Here we show that the polyamine philanthotoxin-7,4 (PhTx-74) is a subtype-selective AMPAR antagonist, inhibiting GluR1/2, but not GluR2/3 receptors, use-dependently. The molecular basis for the observed selectivity and a highly efficient synthesis of this remarkable toxin are also presented. PhTx-74 provides the first a means of directly monitoring subtype-specific changes in the composition of AMPARs at native synapses, including during hippocampal long-term potentiation (LTP), a form of synaptic plasticity thought to share processes related to learning and memory.

  DOI：

  10.1021/ja0705801