ethyl 2-acetamido-2-ethoxycarbonyl-3-(3-ethoxy-5-trifluoromethyl-4-isoxazolyl)propionate | 145433-11-0

• 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: ethyl 2-acetamido-2-ethoxycarbonyl-3-(3-ethoxy-5-trifluoromethyl-4-isoxazolyl)propionate
• 英文别名: Diethyl 2-acetamido-2-[[3-ethoxy-5-(trifluoromethyl)-1,2-oxazol-4-yl]methyl]propanedioate
• CAS: 145433-11-0
• 化学式: C₁₆H₂₁F₃N₂O₇
• 分子量: 410.347
• InChiKey: LCZFGFAVEWJJLA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  28
• 可旋转键数：
  11
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  117
• 氢给体数：
  1
• 氢受体数：
  11

反应信息

• 作为反应物：
  描述：

  ethyl 2-acetamido-2-ethoxycarbonyl-3-(3-ethoxy-5-trifluoromethyl-4-isoxazolyl)propionate 在 氢溴酸 作用下， 反应 0.5h， 以56%的产率得到Trifluoro-AMPA
  参考文献：
  名称：

  Synthesis and pharmacology of (RS)-2-amino-3-(3-hydroxy-5-trifluoromethyl-4-isoxazolyl)propionic acid, a potent AMPA receptor agonist

  摘要：

  Three isoxazole bioisosteres of glutamic acid derived from the specific AMPA receptor agonist (RS)-2-amino-3-(3-hydroxy-5-methyl-4-isoxazolyl)propionic acid (AMPA) were synthesized and tested electrophysiologically and in different receptor binding systems. (RS)-2-Amino-3-(3-hydroxy-5-trifluoromethyl-4-isoxazolyl)propionic acid (trifluoro-AMPA, 8) showed more potent agonist activity (EC50 2.3 muM) and lower affinity (IC50 0.08 muM) for AMPA receptors than AMPA itself (EC, 3.5 muM and IC50 0.04 muM, respectively). Like AMPA, trifluoro-AMPA (8) did not bind significantly to N-methyl-D-aspartic acid (NMDA) receptor sites, but trifluoro-AMPA (8) was more potent as an inhibitor of [H-3]kainic acid ([H-3]KAIN) binding (IC50 7.1 muM) than AMPA (IC50 32 muM). (RS)-2-Amino-3-(3-chloro-5-methyl-4-isoxazolyl)propionic acid (14), the 3-chloro analogue of AMPA, and the isomeric compound (RS)-2-amino-3-(3-chloro-4-methyl-5-isoxazolyl)propionic acid (15), did not show significant neuroexcitatory effects at or affinities for AMPA, NMDA, or KAIN receptor sites.

  DOI：

  10.1016/0223-5234(92)90181-y
• 作为产物：
  描述：

  2-甲基-4,4,4-三氟乙酰乙酸乙酯 在 sodium hydroxide 、 N-溴代丁二酰亚胺(NBS) 、 过氧化氢苯甲酰 、 硫酸 、 盐酸羟胺 、 sodium hydride 、 potassium carbonate 作用下， 以 四氢呋喃 、 四氯化碳 、 水 、 丙酮 为溶剂， 反应 31.5h， 生成 ethyl 2-acetamido-2-ethoxycarbonyl-3-(3-ethoxy-5-trifluoromethyl-4-isoxazolyl)propionate
  参考文献：
  名称：

  Synthesis and pharmacology of (RS)-2-amino-3-(3-hydroxy-5-trifluoromethyl-4-isoxazolyl)propionic acid, a potent AMPA receptor agonist

  摘要：

  Three isoxazole bioisosteres of glutamic acid derived from the specific AMPA receptor agonist (RS)-2-amino-3-(3-hydroxy-5-methyl-4-isoxazolyl)propionic acid (AMPA) were synthesized and tested electrophysiologically and in different receptor binding systems. (RS)-2-Amino-3-(3-hydroxy-5-trifluoromethyl-4-isoxazolyl)propionic acid (trifluoro-AMPA, 8) showed more potent agonist activity (EC50 2.3 muM) and lower affinity (IC50 0.08 muM) for AMPA receptors than AMPA itself (EC, 3.5 muM and IC50 0.04 muM, respectively). Like AMPA, trifluoro-AMPA (8) did not bind significantly to N-methyl-D-aspartic acid (NMDA) receptor sites, but trifluoro-AMPA (8) was more potent as an inhibitor of [H-3]kainic acid ([H-3]KAIN) binding (IC50 7.1 muM) than AMPA (IC50 32 muM). (RS)-2-Amino-3-(3-chloro-5-methyl-4-isoxazolyl)propionic acid (14), the 3-chloro analogue of AMPA, and the isomeric compound (RS)-2-amino-3-(3-chloro-4-methyl-5-isoxazolyl)propionic acid (15), did not show significant neuroexcitatory effects at or affinities for AMPA, NMDA, or KAIN receptor sites.

  DOI：

  10.1016/0223-5234(92)90181-y

文献信息

• Synthesis and pharmacology of (RS)-2-amino-3-(3-hydroxy-5-trifluoromethyl-4-isoxazolyl)propionic acid, a potent AMPA receptor agonist
  作者：U Madsen、B Ebert、P Krogsgaard-Larsen、EHF Wong

  DOI：10.1016/0223-5234(92)90181-y

  日期：1992.8

  Three isoxazole bioisosteres of glutamic acid derived from the specific AMPA receptor agonist (RS)-2-amino-3-(3-hydroxy-5-methyl-4-isoxazolyl)propionic acid (AMPA) were synthesized and tested electrophysiologically and in different receptor binding systems. (RS)-2-Amino-3-(3-hydroxy-5-trifluoromethyl-4-isoxazolyl)propionic acid (trifluoro-AMPA, 8) showed more potent agonist activity (EC50 2.3 muM) and lower affinity (IC50 0.08 muM) for AMPA receptors than AMPA itself (EC, 3.5 muM and IC50 0.04 muM, respectively). Like AMPA, trifluoro-AMPA (8) did not bind significantly to N-methyl-D-aspartic acid (NMDA) receptor sites, but trifluoro-AMPA (8) was more potent as an inhibitor of [H-3]kainic acid ([H-3]KAIN) binding (IC50 7.1 muM) than AMPA (IC50 32 muM). (RS)-2-Amino-3-(3-chloro-5-methyl-4-isoxazolyl)propionic acid (14), the 3-chloro analogue of AMPA, and the isomeric compound (RS)-2-amino-3-(3-chloro-4-methyl-5-isoxazolyl)propionic acid (15), did not show significant neuroexcitatory effects at or affinities for AMPA, NMDA, or KAIN receptor sites.