ethyl 2-tetrazol-5-yl-2-methoximinoacetate | 144493-35-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: ethyl 2-tetrazol-5-yl-2-methoximinoacetate
• 英文别名: ethyl-2-methoxyimino-2-(1H-tetrazol-5-yl)-acetate；ethyl 2-methoxyimino-2-(2H-tetrazol-5-yl)acetate
• CAS: 144493-35-6
• 化学式: C₆H₉N₅O₃
• 分子量: 199.169
• InChiKey: YDPCBMKLSZWGBF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.5
• 重原子数：
  14
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  102
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  ethyl 2-tetrazol-5-yl-2-methoximinoacetate 在 sodium hydroxide 作用下， 反应 1.7h， 以99%的产率得到2-tetrazol-5-yl-2-methoximinoacetic acid
  参考文献：
  名称：

  DL-Tetrazol-5-ylglycine, a highly potent NMDA agonist: its synthesis and NMDA receptor efficacy

  摘要：

  At physiological pH, the spatial arrangement of the three charges Of DL-tetrazol-5-ylglycine (5) could be viewed as similar to those found in certain conformations of the two excitatory amino acids (EAAs)-aspartic and glutamic acids. Given significant binding to one or more EAA receptors, 5 would offer unique modeling and perhaps biological opportunities. We have previously shown it to be the most potent NMDA agonist known, with a unique and marked in vitro neutrotoxicity at depolarizing concentrations. Now we report the details required for its synthesis, together with its potency and efficacy in two assays of functional activation of the NMDA receptor, namely agonist-influenced [H-3]MK801 binding and agonist-induced release of the neurotransmitter [H-3]-norepinephrine from brain slices. In both these assays DL-tetrazol-5-ylglycine proved to be more potent and efficacious than NMDA and cis-methanoglutamate. It was more potent than, and equally efficacious to, L-glutamate in [H-3]MK801 binding. The structural features of 5 may well reflect optimal agonist interaction at the NMDA receptor site. (We considered the possibility that some decarboxylation of DL-tetrazol-5-ylglycine may have occurred during testing. This would give 5-(aminomethyl)tetrazole (13), the tetrazole acid analog of glycine; and glycine is involved in NMDA receptor activation. Compound 13 does not affect [H-3]glycine binding at the strychnine-insensitive glycine binding site, and [H-3]MK801 binding studies showed that the (aminomethyl)-tetrazole, even if is formed, would probably have no effect on the activity of tetrazol-5-ylglycine at the NMDA receptor.)

  DOI：

  10.1021/jm00102a015
• 作为产物：
  描述：

  2-肟氰乙酸乙酯 在 盐酸 、 potassium carbonate 、 三正丁基叠氮化锡 作用下， 以 丙酮 为溶剂， 反应 4.97h， 生成 ethyl 2-tetrazol-5-yl-2-methoximinoacetate
  参考文献：
  名称：

  DL-Tetrazol-5-ylglycine, a highly potent NMDA agonist: its synthesis and NMDA receptor efficacy

  摘要：

  At physiological pH, the spatial arrangement of the three charges Of DL-tetrazol-5-ylglycine (5) could be viewed as similar to those found in certain conformations of the two excitatory amino acids (EAAs)-aspartic and glutamic acids. Given significant binding to one or more EAA receptors, 5 would offer unique modeling and perhaps biological opportunities. We have previously shown it to be the most potent NMDA agonist known, with a unique and marked in vitro neutrotoxicity at depolarizing concentrations. Now we report the details required for its synthesis, together with its potency and efficacy in two assays of functional activation of the NMDA receptor, namely agonist-influenced [H-3]MK801 binding and agonist-induced release of the neurotransmitter [H-3]-norepinephrine from brain slices. In both these assays DL-tetrazol-5-ylglycine proved to be more potent and efficacious than NMDA and cis-methanoglutamate. It was more potent than, and equally efficacious to, L-glutamate in [H-3]MK801 binding. The structural features of 5 may well reflect optimal agonist interaction at the NMDA receptor site. (We considered the possibility that some decarboxylation of DL-tetrazol-5-ylglycine may have occurred during testing. This would give 5-(aminomethyl)tetrazole (13), the tetrazole acid analog of glycine; and glycine is involved in NMDA receptor activation. Compound 13 does not affect [H-3]glycine binding at the strychnine-insensitive glycine binding site, and [H-3]MK801 binding studies showed that the (aminomethyl)-tetrazole, even if is formed, would probably have no effect on the activity of tetrazol-5-ylglycine at the NMDA receptor.)

  DOI：

  10.1021/jm00102a015

文献信息

• DL-Tetrazol-5-ylglycine, a highly potent NMDA agonist: its synthesis and NMDA receptor efficacy
  作者：W. H. W. Lunn、Darryle D. Schoepp、David O. Calligaro、R. T. Vasileff、L. J. Heinz、Craig R. Salhoff、Patrick J. O'Malley

  DOI：10.1021/jm00102a015

  日期：1992.11

  At physiological pH, the spatial arrangement of the three charges Of DL-tetrazol-5-ylglycine (5) could be viewed as similar to those found in certain conformations of the two excitatory amino acids (EAAs)-aspartic and glutamic acids. Given significant binding to one or more EAA receptors, 5 would offer unique modeling and perhaps biological opportunities. We have previously shown it to be the most potent NMDA agonist known, with a unique and marked in vitro neutrotoxicity at depolarizing concentrations. Now we report the details required for its synthesis, together with its potency and efficacy in two assays of functional activation of the NMDA receptor, namely agonist-influenced [H-3]MK801 binding and agonist-induced release of the neurotransmitter [H-3]-norepinephrine from brain slices. In both these assays DL-tetrazol-5-ylglycine proved to be more potent and efficacious than NMDA and cis-methanoglutamate. It was more potent than, and equally efficacious to, L-glutamate in [H-3]MK801 binding. The structural features of 5 may well reflect optimal agonist interaction at the NMDA receptor site. (We considered the possibility that some decarboxylation of DL-tetrazol-5-ylglycine may have occurred during testing. This would give 5-(aminomethyl)tetrazole (13), the tetrazole acid analog of glycine; and glycine is involved in NMDA receptor activation. Compound 13 does not affect [H-3]glycine binding at the strychnine-insensitive glycine binding site, and [H-3]MK801 binding studies showed that the (aminomethyl)-tetrazole, even if is formed, would probably have no effect on the activity of tetrazol-5-ylglycine at the NMDA receptor.)