Ethyl 4-(3,7-dioxo-2,4,5,8,10-pentazatricyclo[7.4.0.02,6]trideca-1(9),5,10,12-tetraen-4-yl)benzoate | 1144160-91-7

• 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 4-(3,7-dioxo-2,4,5,8,10-pentazatricyclo[7.4.0.02,6]trideca-1(9),5,10,12-tetraen-4-yl)benzoate
• CAS: 1144160-91-7
• 化学式: C₁₇H₁₃N₅O₄
• 分子量: 351.321
• InChiKey: QUVDJSCMZDIXDF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  26
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  104
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  Ethyl 4-(3,7-dioxo-2,4,5,8,10-pentazatricyclo[7.4.0.02,6]trideca-1(9),5,10,12-tetraen-4-yl)benzoate 在 吡啶 、 五氯化磷 、 三氯氧磷 作用下， 生成 Ethyl 4-(7-chloro-3-oxo-2,4,5,8,10-pentazatricyclo[7.4.0.02,6]trideca-1(9),5,7,10,12-pentaen-4-yl)benzoate
  参考文献：
  名称：

  Pyrido[2,3-e]-1,2,4-triazolo[4,3-a]pyrazin-1-one as a New Scaffold To Develop Potent and Selective Human A₃ Adenosine Receptor Antagonists. Synthesis, Pharmacological Evaluation, and Ligand−Receptor Modeling Studies

  摘要：

  The paper describes a new class of human (h) A(3) adenosine receptor antagonists, the 2-arylpyrido[2,3-e]-1,2,4-triazolo[4,3-a]pyrazin-1-one derivatives (PTP), either 4-oxo (1-6, series A) or 4-amino-substituted (7-20, series B). In both series A and B, substituents able to act as hydrogen bond acceptors (OMe, OH. F. COOEt) were inserted on the 2-phenyl ring. In series B, cycloalkyl and acyl residues were introduced on the 4-amino group. Some of the new derivatives showed high hA(3) AR affinities (K-i < 50 nM) and selectivities vs both hA(1) and hA(2A) receptors. The selected 4-benzoylamino-2-(4-methoxyphenyl)pyrido[2,3-e]-1,2,4-triazolo[4,3-a]pyrazin-1-one (18), tested in an in vitro rat model of cerebral ischemia, proved to be effective in preventing the failure of synaptic activity induced by oxygen and glucose deprivation in the hippocampus. Molecular docking of this new class of hA(3) AR antagonists was carried out to depict their hypothetical binding mode to our refined model of hA(3) receptor.

  DOI：

  10.1021/jm8014876
• 作为产物：
  描述：

  三光气 、 ethyl 4-[2-(3-oxo-4H-pyrido[2,3-b]pyrazin-2-yl)hydrazinyl]benzoate 以 四氢呋喃 为溶剂， 以45%的产率得到Ethyl 4-(3,7-dioxo-2,4,5,8,10-pentazatricyclo[7.4.0.02,6]trideca-1(9),5,10,12-tetraen-4-yl)benzoate
  参考文献：
  名称：

  Pyrido[2,3-e]-1,2,4-triazolo[4,3-a]pyrazin-1-one as a New Scaffold To Develop Potent and Selective Human A₃ Adenosine Receptor Antagonists. Synthesis, Pharmacological Evaluation, and Ligand−Receptor Modeling Studies

  摘要：

  The paper describes a new class of human (h) A(3) adenosine receptor antagonists, the 2-arylpyrido[2,3-e]-1,2,4-triazolo[4,3-a]pyrazin-1-one derivatives (PTP), either 4-oxo (1-6, series A) or 4-amino-substituted (7-20, series B). In both series A and B, substituents able to act as hydrogen bond acceptors (OMe, OH. F. COOEt) were inserted on the 2-phenyl ring. In series B, cycloalkyl and acyl residues were introduced on the 4-amino group. Some of the new derivatives showed high hA(3) AR affinities (K-i < 50 nM) and selectivities vs both hA(1) and hA(2A) receptors. The selected 4-benzoylamino-2-(4-methoxyphenyl)pyrido[2,3-e]-1,2,4-triazolo[4,3-a]pyrazin-1-one (18), tested in an in vitro rat model of cerebral ischemia, proved to be effective in preventing the failure of synaptic activity induced by oxygen and glucose deprivation in the hippocampus. Molecular docking of this new class of hA(3) AR antagonists was carried out to depict their hypothetical binding mode to our refined model of hA(3) receptor.

  DOI：

  10.1021/jm8014876

文献信息

• Pyrido[2,3-<i>e</i>]-1,2,4-triazolo[4,3-<i>a</i>]pyrazin-1-one as a New Scaffold To Develop Potent and Selective Human A₃ Adenosine Receptor Antagonists. Synthesis, Pharmacological Evaluation, and Ligand−Receptor Modeling Studies
  作者：Vittoria Colotta、Ombretta Lenzi、Daniela Catarzi、Flavia Varano、Guido Filacchioni、Claudia Martini、Letizia Trincavelli、Osele Ciampi、Anna Maria Pugliese、Chiara Traini、Felicita Pedata、Erika Morizzo、Stefano Moro

  DOI：10.1021/jm8014876

  日期：2009.4.23

  The paper describes a new class of human (h) A(3) adenosine receptor antagonists, the 2-arylpyrido[2,3-e]-1,2,4-triazolo[4,3-a]pyrazin-1-one derivatives (PTP), either 4-oxo (1-6, series A) or 4-amino-substituted (7-20, series B). In both series A and B, substituents able to act as hydrogen bond acceptors (OMe, OH. F. COOEt) were inserted on the 2-phenyl ring. In series B, cycloalkyl and acyl residues were introduced on the 4-amino group. Some of the new derivatives showed high hA(3) AR affinities (K-i < 50 nM) and selectivities vs both hA(1) and hA(2A) receptors. The selected 4-benzoylamino-2-(4-methoxyphenyl)pyrido[2,3-e]-1,2,4-triazolo[4,3-a]pyrazin-1-one (18), tested in an in vitro rat model of cerebral ischemia, proved to be effective in preventing the failure of synaptic activity induced by oxygen and glucose deprivation in the hippocampus. Molecular docking of this new class of hA(3) AR antagonists was carried out to depict their hypothetical binding mode to our refined model of hA(3) receptor.