methyl 2-methoxycarbonyl-3-[3-(bromomethyl)-5-methyl-4-isoxazolyl]propionate | 266341-66-6

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: methyl 2-methoxycarbonyl-3-[3-(bromomethyl)-5-methyl-4-isoxazolyl]propionate
• 英文别名: Dimethyl 2-[[3-(bromomethyl)-5-methyl-1,2-oxazol-4-yl]methyl]propanedioate
• CAS: 266341-66-6
• 化学式: C₁₁H₁₄BrNO₅
• 分子量: 320.14
• InChiKey: NZTDCTMMDKXDGX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  18
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  78.6
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  methyl 2-methoxycarbonyl-3-[3-(bromomethyl)-5-methyl-4-isoxazolyl]propionate 在 盐酸 、 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 16.5h， 生成 2-Amino-3-[4-(2-carboxy-ethyl)-5-methyl-isoxazol-3-yl]-propionic acid
  参考文献：
  名称：

  Ionotropic excitatory amino acid receptor ligands. Synthesis and pharmacology of a new amino acid AMPA antagonist

  摘要：

  We have previously described the potent and selective (RS)-2-amino-3-(3-hydroxy-5-methyl-5-isoxazolyl)propionic acid (AMPA) receptor agonist, (RS)-2-amino-3-(3-carboxy-5-merhyl-4-isoxazolyl)propionic acid (ACPA), and the AMPA receptor antagonist (RS)-2-amino3-[3-(carboxymethoxy)-5-methyl-4-isoxazolyl]propionic acid (AMOA). Using these AMPA receptor ligands as leads, a series of compounds have been developed as tools for further elucidation of the structural requirements for activation and blockade of AMPA receptors. The synthesized compounds have been tested for activity at ionotropic excitatory amino acid (EAA) receptors using receptor binding and electrophysiological techniques, and for activity at metabotropic EAA receptors using second messenger assays. Compounds 1 and 4 were essentially inactive. (RS)-2-Amino-3-[3-(2-carboxyethyl)-5-methyl-4-isoxazoly]propionic acid (ACMP, 2), on the other hand, was shown to be a selective AMPA receptor antagonist (IC50 = 73 mu M), more potent in electrophysiological experiments than AMOA (IC50 = 320 mu M). The isomeric analogue of 2, compound 5, did not show AMPA antagonist effects, but was a weak NMDA receptor antagonist (IC50 = 540 mu M). Finally, compound 3, which is an isomer of ACPA, turned out to be a very weak NMDA antagonist, and an AMPA receptor agonist approximately 1 000 times weaker than ACPA. None of the compounds showed agonist or antagonist effects at metabotropic EAA receptors. (C) 2000 Editions scientifiques et medicales Elsevier SAS.

  DOI：

  10.1016/s0223-5234(00)00104-5
• 作为产物：
  描述：

  丙二酸二甲酯 、 3,4-di(bromomethyl)-5-methylisoxazole 在 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 0.5h， 生成 methyl 2-methoxycarbonyl-3-[3-(bromomethyl)-5-methyl-4-isoxazolyl]propionate
  参考文献：
  名称：

  Ionotropic excitatory amino acid receptor ligands. Synthesis and pharmacology of a new amino acid AMPA antagonist

  摘要：

  We have previously described the potent and selective (RS)-2-amino-3-(3-hydroxy-5-methyl-5-isoxazolyl)propionic acid (AMPA) receptor agonist, (RS)-2-amino-3-(3-carboxy-5-merhyl-4-isoxazolyl)propionic acid (ACPA), and the AMPA receptor antagonist (RS)-2-amino3-[3-(carboxymethoxy)-5-methyl-4-isoxazolyl]propionic acid (AMOA). Using these AMPA receptor ligands as leads, a series of compounds have been developed as tools for further elucidation of the structural requirements for activation and blockade of AMPA receptors. The synthesized compounds have been tested for activity at ionotropic excitatory amino acid (EAA) receptors using receptor binding and electrophysiological techniques, and for activity at metabotropic EAA receptors using second messenger assays. Compounds 1 and 4 were essentially inactive. (RS)-2-Amino-3-[3-(2-carboxyethyl)-5-methyl-4-isoxazoly]propionic acid (ACMP, 2), on the other hand, was shown to be a selective AMPA receptor antagonist (IC50 = 73 mu M), more potent in electrophysiological experiments than AMOA (IC50 = 320 mu M). The isomeric analogue of 2, compound 5, did not show AMPA antagonist effects, but was a weak NMDA receptor antagonist (IC50 = 540 mu M). Finally, compound 3, which is an isomer of ACPA, turned out to be a very weak NMDA antagonist, and an AMPA receptor agonist approximately 1 000 times weaker than ACPA. None of the compounds showed agonist or antagonist effects at metabotropic EAA receptors. (C) 2000 Editions scientifiques et medicales Elsevier SAS.

  DOI：

  10.1016/s0223-5234(00)00104-5

文献信息

• Ionotropic excitatory amino acid receptor ligands. Synthesis and pharmacology of a new amino acid AMPA antagonist
  作者：U Madsen

  DOI：10.1016/s0223-5234(00)00104-5

  日期：2000.1

  We have previously described the potent and selective (RS)-2-amino-3-(3-hydroxy-5-methyl-5-isoxazolyl)propionic acid (AMPA) receptor agonist, (RS)-2-amino-3-(3-carboxy-5-merhyl-4-isoxazolyl)propionic acid (ACPA), and the AMPA receptor antagonist (RS)-2-amino3-[3-(carboxymethoxy)-5-methyl-4-isoxazolyl]propionic acid (AMOA). Using these AMPA receptor ligands as leads, a series of compounds have been developed as tools for further elucidation of the structural requirements for activation and blockade of AMPA receptors. The synthesized compounds have been tested for activity at ionotropic excitatory amino acid (EAA) receptors using receptor binding and electrophysiological techniques, and for activity at metabotropic EAA receptors using second messenger assays. Compounds 1 and 4 were essentially inactive. (RS)-2-Amino-3-[3-(2-carboxyethyl)-5-methyl-4-isoxazoly]propionic acid (ACMP, 2), on the other hand, was shown to be a selective AMPA receptor antagonist (IC50 = 73 mu M), more potent in electrophysiological experiments than AMOA (IC50 = 320 mu M). The isomeric analogue of 2, compound 5, did not show AMPA antagonist effects, but was a weak NMDA receptor antagonist (IC50 = 540 mu M). Finally, compound 3, which is an isomer of ACPA, turned out to be a very weak NMDA antagonist, and an AMPA receptor agonist approximately 1 000 times weaker than ACPA. None of the compounds showed agonist or antagonist effects at metabotropic EAA receptors. (C) 2000 Editions scientifiques et medicales Elsevier SAS.