ethyl 2-tetrazol-5-yl-2-oximinoacetate | 112472-44-3

• 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-oximinoacetate
• 英文别名: ethyl 5-tetrazolylacetate oxime；ethyl 2-(hydroxyimino)-2-(1H-tetrazol-5-yl)acetate；ethyl 2-hydroxyimino-2-(2H-tetrazol-5-yl)acetate
• CAS: 112472-44-3
• 化学式: C₅H₇N₅O₃
• 分子量: 185.142
• InChiKey: WCNZUCUGJZIMTR-UHFFFAOYSA-N

物化性质

• 熔点：
  178-179 °C
• 沸点：
  408.7±28.0 °C(Predicted)
• 密度：
  1.70±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  13
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  113
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  ethyl 2-tetrazol-5-yl-2-oximinoacetate 在 Pearlman's catalyst 、 氢气 、 盐酸 作用下， 以 甲醇 为溶剂， 反应 20.0h， 以100%的产率得到(2R,S)-amino-2-(1H-tetrazol-5-yl)acetic acid ethyl ester hydrochloride
  参考文献：
  名称：

  Potential Neuroprotective Drugs in Cerebral Ischemia: New Saturated and Polyunsaturated Lipids Coupled to Hydrophilic Moieties: Synthesis and Biological Activity

  摘要：

  The ganglioside GM1 has neuroprotective effects but is not of therapeutic value because of its lack of bioavailability. Thus, molecules that mimic GM I represent a novel approach to neuroprotection. We have synthesized 19 small GM1-like analogues whose simplified structure includes a hydrophobic saturated or unsaturated moiety linked to a hydrophilic moiety. We report their neuroprotective effects in two distinct models of nerve cell death using hippocampus-derived HT22 cells. We found that several analogues protected the HT22 cells from death at concentrations ranging from 2 to 5 mu M. Additional neuroprotective assays using cortical slices injured by glutamate confirmed these results. Since members of the MAP kinase family are known to be key players in nerve cell survival and death, we characterized the role of these kinases in the neuroprotective mechanisms of the GM1-like analogues. Interestingly, the results indicate that the compounds provide neuroprotection through distinct mechanisms of action.

  DOI：

  10.1021/jm900227u
• 作为产物：
  描述：

  2-肟氰乙酸乙酯 在 sodium azide 、 盐酸 、 水 作用下， 以 N,N-二甲基甲酰胺 、 水 、 乙酸乙酯 为溶剂， 反应 30.0h， 以39%的产率得到ethyl 2-tetrazol-5-yl-2-oximinoacetate
  参考文献：
  名称：

  Potential Neuroprotective Drugs in Cerebral Ischemia: New Saturated and Polyunsaturated Lipids Coupled to Hydrophilic Moieties: Synthesis and Biological Activity

  摘要：

  The ganglioside GM1 has neuroprotective effects but is not of therapeutic value because of its lack of bioavailability. Thus, molecules that mimic GM I represent a novel approach to neuroprotection. We have synthesized 19 small GM1-like analogues whose simplified structure includes a hydrophobic saturated or unsaturated moiety linked to a hydrophilic moiety. We report their neuroprotective effects in two distinct models of nerve cell death using hippocampus-derived HT22 cells. We found that several analogues protected the HT22 cells from death at concentrations ranging from 2 to 5 mu M. Additional neuroprotective assays using cortical slices injured by glutamate confirmed these results. Since members of the MAP kinase family are known to be key players in nerve cell survival and death, we characterized the role of these kinases in the neuroprotective mechanisms of the GM1-like analogues. Interestingly, the results indicate that the compounds provide neuroprotection through distinct mechanisms of action.

  DOI：

  10.1021/jm900227u

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.)
• Terpigorev, A. N.; Tselinskii, I. V.; Makarevich, A. V., Journal of Organic Chemistry USSR (English Translation), 1987, vol. 23, p. 214 - 222
  作者：Terpigorev, A. N.、Tselinskii, I. V.、Makarevich, A. V.、Frolova, G. M.、Mel'nikov, A. A.

  DOI：——

  日期：——
• Potential Neuroprotective Drugs in Cerebral Ischemia: New Saturated and Polyunsaturated Lipids Coupled to Hydrophilic Moieties: Synthesis and Biological Activity
  作者：Alain César Biraboneye、Sébastien Madonna、Younes Laras、Slavica Krantic、Pamela Maher、Jean-Louis Kraus

  DOI：10.1021/jm900227u

  日期：2009.7.23

  The ganglioside GM1 has neuroprotective effects but is not of therapeutic value because of its lack of bioavailability. Thus, molecules that mimic GM I represent a novel approach to neuroprotection. We have synthesized 19 small GM1-like analogues whose simplified structure includes a hydrophobic saturated or unsaturated moiety linked to a hydrophilic moiety. We report their neuroprotective effects in two distinct models of nerve cell death using hippocampus-derived HT22 cells. We found that several analogues protected the HT22 cells from death at concentrations ranging from 2 to 5 mu M. Additional neuroprotective assays using cortical slices injured by glutamate confirmed these results. Since members of the MAP kinase family are known to be key players in nerve cell survival and death, we characterized the role of these kinases in the neuroprotective mechanisms of the GM1-like analogues. Interestingly, the results indicate that the compounds provide neuroprotection through distinct mechanisms of action.