ethyl 8-amino-4,5-dihydro-4-oxo-1,2,4-triazolo[1,5-a]quinoxaline-2-carboxylate | 366804-04-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: ethyl 8-amino-4,5-dihydro-4-oxo-1,2,4-triazolo[1,5-a]quinoxaline-2-carboxylate
• 英文别名: 8-Amino-4-oxo-4,5-dihydro-[1,2,4]triazolo[1,5-a]quinoxaline-2-carboxylic acid ethyl ester；ethyl 8-amino-4-oxo-5H-[1,2,4]triazolo[1,5-a]quinoxaline-2-carboxylate
• CAS: 366804-04-8
• 化学式: C₁₂H₁₁N₅O₃
• 分子量: 273.251
• InChiKey: NYZSNSJFTMYHRW-UHFFFAOYSA-N

物化性质

• 密度：
  1.68±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  20
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  112
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  ethyl 8-amino-4,5-dihydro-4-oxo-1,2,4-triazolo[1,5-a]quinoxaline-2-carboxylate 在 吡啶 、 sodium hydroxide 、 三甲基氯硅烷 、 三乙胺 作用下， 以 乙醇 为溶剂， 反应 3.0h， 生成 4-oxo-8-(1,2,4-triazol-4-yl)-5H-[1,2,4]triazolo[1,5-a]quinoxaline-2-carboxylic acid
  参考文献：
  名称：

  Synthesis, Ionotropic Glutamate Receptor Binding Affinity, and Structure−Activity Relationships of a New Set of 4,5-Dihydro-8-heteroaryl-4-oxo-1,2,4-triazolo[1,5-a]quinoxaline-2-carboxylates Analogues of TQX-173

  摘要：

  A seires of 4,5-dihydro-4-oxo-1,2,4-triazolo[1,5-a]quinoxaline-2-carboxylates analogues of TQX-173 (1b), bearing different nitrogen-containing heterocycles at position-8, were synthesized as AMPA receptor antagonists. All the reported compounds were also biologically evaluated for their binding at glycine/NMDA and KA receptors to better assess their selectivity toward the AMPA receptor. Structure-activity relationships (SAR) on these TQX derivatives have evidenced that the precise positioning of the nitrogen atoms and the specific electronic topography of the 8-heteroaromatic ring are both important for the anchoring to the AMPA receptor. In fact, it has been well-established that the presence of a N-3-nitrogen-containing heterocycle at position-8 of the TQX framework is an essential feature for potent and selective AMPA receptor antagonists. Functional antagonism at both AMPA receptor and NMDA receptor-ion channel complex was evaluated by assessing the ability of some selected compounds to inhibit depolarization induced by 5 muM AMPA or NMDA in mouse cortical wedge preparations.

  DOI：

  10.1021/jm010862q
• 作为产物：
  描述：

  [1,2,4]三唑并[1,5-a]喹喔啉-2-羧酸,4,5-二氢-4-羰基-,乙基酯 在 铁粉 、 溶剂黄146 作用下， 反应 0.5h， 生成 ethyl 8-amino-4,5-dihydro-4-oxo-1,2,4-triazolo[1,5-a]quinoxaline-2-carboxylate
  参考文献：
  名称：

  Synthesis, Ionotropic Glutamate Receptor Binding Affinity, and Structure−Activity Relationships of a New Set of 4,5-Dihydro-8-heteroaryl-4-oxo-1,2,4-triazolo[1,5-a]quinoxaline-2-carboxylates Analogues of TQX-173

  摘要：

  A seires of 4,5-dihydro-4-oxo-1,2,4-triazolo[1,5-a]quinoxaline-2-carboxylates analogues of TQX-173 (1b), bearing different nitrogen-containing heterocycles at position-8, were synthesized as AMPA receptor antagonists. All the reported compounds were also biologically evaluated for their binding at glycine/NMDA and KA receptors to better assess their selectivity toward the AMPA receptor. Structure-activity relationships (SAR) on these TQX derivatives have evidenced that the precise positioning of the nitrogen atoms and the specific electronic topography of the 8-heteroaromatic ring are both important for the anchoring to the AMPA receptor. In fact, it has been well-established that the presence of a N-3-nitrogen-containing heterocycle at position-8 of the TQX framework is an essential feature for potent and selective AMPA receptor antagonists. Functional antagonism at both AMPA receptor and NMDA receptor-ion channel complex was evaluated by assessing the ability of some selected compounds to inhibit depolarization induced by 5 muM AMPA or NMDA in mouse cortical wedge preparations.

  DOI：

  10.1021/jm010862q

文献信息

• Synthesis and Biological Evaluation of Analogues of 7-Chloro-4,5-dihydro-4- oxo-8-(1,2,4-triazol-4-yl)-1,2,4-triazolo[1,5-<i>a</i>]quinoxaline-2-carboxylic Acid (TQX-173) as Novel Selective AMPA Receptor Antagonists
  作者：Daniela Catarzi、Vittoria Colotta、Flavia Varano、Francesca Romana Calabri、Guido Filacchioni、Alessandro Galli、Chiara Costagli、Vincenzo Carlà

  DOI：10.1021/jm030906q

  日期：2004.1.1

  In recent papers (Catarzi, D.; et al. J. Med. Chem. 2000, 43, 3824-3826; 2001, 44, 31573165) we reported chemical and biological studies on 4,5-dihydro-4-oxo-1,2,4-triazolo[1,5-a]-quinoxaline-2-carboxylates (TQXs) bearing different nitrogen-containing heterocycles at position-8. In particular, from these studies it emerged that both the 7-chloro-4,5-dihydro-4-oxo-8-(1,2,4-triazol-4-yl)-1,2,4-triazolo[1,5-a] quinoxaline-2-carboxylic acid TQX-173 (compound B) and its corresponding ethyl ester (compound A) were the most active and selective compounds of this series. In pursuing our investigation on the structure-activity relationships of these TQX derivatives, different electron-withdrawing groups (CF3, NO2) were introduced at position 7 on the TQX ring system, replacing the 7-chloro substituent of B and of other selected 8-heteroaryltriazoloquinoxaline-2-carboxylates previously described. All the newly synthesized compounds were biologically evaluated for their binding at the Gly/NMDA, AMPA, and KA high-affinity receptors. Gly/NMDA binding assays were performed to assess the selectivity of the reported compounds toward the AMPA receptor. Compounds endowed with micromolar binding affinity for the KA high-affinity binding site were also evaluated for their binding at the KA low-affinity receptor. Some selected compounds were also tested for their functional antagonist activity at the AMPA and NMDA receptor-ion channel complex. The results obtained in this study have pointed out that 4,5-dihydro-7-nitro-4-oxo-8-(3-carboxypyrrol-1-yl)-1,2,4-triazolo[1,5-alquinoxaline-2-carboxylic acid (9b) and its corresponding ethyl ester (9a) are the most potent and selective AMPA receptor antagonists reported to date among the TQX series.
• Synthesis, Ionotropic Glutamate Receptor Binding Affinity, and Structure−Activity Relationships of a New Set of 4,5-Dihydro-8-heteroaryl-4-oxo-1,2,4-triazolo[1,5-<i>a</i>]quinoxaline-2-carboxylates Analogues of TQX-173
  作者：Daniela Catarzi、Vittoria Colotta、Flavia Varano、Guido Filacchioni、Alessandro Galli、Chiara Costagli、Vincenzo Carlà

  DOI：10.1021/jm010862q

  日期：2001.9.1

  A seires of 4,5-dihydro-4-oxo-1,2,4-triazolo[1,5-a]quinoxaline-2-carboxylates analogues of TQX-173 (1b), bearing different nitrogen-containing heterocycles at position-8, were synthesized as AMPA receptor antagonists. All the reported compounds were also biologically evaluated for their binding at glycine/NMDA and KA receptors to better assess their selectivity toward the AMPA receptor. Structure-activity relationships (SAR) on these TQX derivatives have evidenced that the precise positioning of the nitrogen atoms and the specific electronic topography of the 8-heteroaromatic ring are both important for the anchoring to the AMPA receptor. In fact, it has been well-established that the presence of a N-3-nitrogen-containing heterocycle at position-8 of the TQX framework is an essential feature for potent and selective AMPA receptor antagonists. Functional antagonism at both AMPA receptor and NMDA receptor-ion channel complex was evaluated by assessing the ability of some selected compounds to inhibit depolarization induced by 5 muM AMPA or NMDA in mouse cortical wedge preparations.