ethyl 7-chloro-4,5-dihydro-4-oxo-1,2,4-triazolo[1,5-a]quinoxaline-2-carboxylate | 237420-74-5

• 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 7-chloro-4,5-dihydro-4-oxo-1,2,4-triazolo[1,5-a]quinoxaline-2-carboxylate
• 英文别名: Ethyl 7-chloro-4-oxo-4,5-dihydro-[1,2,4]triazolo[1,5-a]quinoxaline-2-carboxylate；ethyl 7-chloro-4-oxo-5H-[1,2,4]triazolo[1,5-a]quinoxaline-2-carboxylate
• CAS: 237420-74-5
• 化学式: C₁₂H₉ClN₄O₃
• 分子量: 292.681
• InChiKey: DXAANXIRAMZBPL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 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：
  86.1
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  ethyl 7-chloro-4,5-dihydro-4-oxo-1,2,4-triazolo[1,5-a]quinoxaline-2-carboxylate 在 锂硼氢 、 三溴化磷 作用下， 以 四氢呋喃 为溶剂， 反应 32.0h， 生成 2-(bromomethyl)-7-chloro-4,5-dihydro-1,2,4-triazolo<1,5-a>quinoxalin-4-one
  参考文献：
  名称：

  4,5-Dihydro-1,2,4-triazolo[1,5-a]quinoxalin-4-ones:  Excitatory Amino Acid Antagonists with Combined Glycine/NMDA and AMPA Receptor Affinity

  摘要：

  A series of 4,5-dihydro-1,2,4-triazolo[1,5-alpha]quinoxalin-4-ones bearing different substituents on the benzo-fused ring and at position 2 were synthesized and biologically evaluated for their binding at glycine/NMDA and AMPA receptors. Most of the reported compounds show combined glycine/NMDA and AMPA receptor binding activity providing further evidences of the structural similarities of the binding pockets of both receptor recognition sites. Moreover, this study has pointed out some differences for the binding at each receptor type. In particular, for the glycine/NMDA receptor-ligand interaction, the presence of a free acidic function at position 2 and an electron-withdrawing substituent(s) nonbulkier than chlorine atom(s) on the benzo-fused moiety is required. Functional antagonism at the NMDA receptor-ion channel complex was also performed on some selected compounds.

  DOI：

  10.1021/jm981102r
• 作为产物：
  描述：

  4-氯-2-硝基苯胺 在 盐酸 、 氨 、 铁粉 、 溶剂黄146 、 sodium nitrite 作用下， 以 1,4-二氧六环 、 甲醇 、 乙醚 为溶剂， 生成 ethyl 7-chloro-4,5-dihydro-4-oxo-1,2,4-triazolo[1,5-a]quinoxaline-2-carboxylate
  参考文献：
  名称：

  1,2,4-Triazolo[1,5-a]quinoxaline as a Versatile Tool for the Design of Selective Human A₃ Adenosine Receptor Antagonists:  Synthesis, Biological Evaluation, and Molecular Modeling Studies of 2-(Hetero)aryl- and 2-Carboxy-Substitued Derivatives

  摘要：

  A number of 4-oxo-substituted 1,2,4-triazolo[1,5-alquinoxaline derivatives bearing at position-2 the claimed (hetero)aryl moiety (compounds 1-15) but also a carboxylate group (16-28, 3236) or a hydrogen atom (29-31) were designed as human A(3) (hA(3)) adenosine receptor (AR) antagonists. This study produced some interesting compounds and among them the 2-(4methoxyphenyl)-1,2,4-triazolo[1,5-alquinoxalin-4-one (8), which can be considered one of the most potent and selective hA(3) adenosine receptor antagonists reported till now. Moreover, as a new finding, replacement of the classical 2-(hetero)aryl moiety with a 2-carboxylate function (compounds 16-28 and 32-36) maintained good hA(3) AR binding activity but, most importantly and interestingly, produced a large increase in bA(3) versus hA(1) selectivity. A receptor-based SAR analysis provided new interesting insights about the steric and electrostatic requirements that are important for the anchoring of these derivatives at the hA(3) receptor recognition site, thus highlighting the versatility of the triazoloquinoxaline scaffold for obtaining potent and selective hA(3) AR antagonists.

  DOI：

  10.1021/jm0504149

文献信息

• 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.
• 7-Chloro-4,5-dihydro-8-(1,2,4-triazol-4-yl)- 4-oxo-1,2,4-triazolo[1,5-<i>a</i>]quinoxaline-2- carboxylates as Novel Highly Selective AMPA Receptor Antagonists
  作者：Daniela Catarzi、Vittoria Colotta、Flavia Varano、Lucia Cecchi、Guido Filacchioni、Alessandro Galli、Chiara Costagli、Vincenzo Carlà

  DOI：10.1021/jm0009686

  日期：2000.10.1
• 1,2,4-Triazolo[1,5-<i>a</i>]quinoxaline as a Versatile Tool for the Design of Selective Human A₃ Adenosine Receptor Antagonists:  Synthesis, Biological Evaluation, and Molecular Modeling Studies of 2-(Hetero)aryl- and 2-Carboxy-Substitued Derivatives
  作者：Daniela Catarzi、Vittoria Colotta、Flavia Varano、Ombretta Lenzi、Guido Filacchioni、Letizia Trincavelli、Claudia Martini、Christian Montopoli、Stefano Moro

  DOI：10.1021/jm0504149

  日期：2005.12.1

  A number of 4-oxo-substituted 1,2,4-triazolo[1,5-alquinoxaline derivatives bearing at position-2 the claimed (hetero)aryl moiety (compounds 1-15) but also a carboxylate group (16-28, 3236) or a hydrogen atom (29-31) were designed as human A(3) (hA(3)) adenosine receptor (AR) antagonists. This study produced some interesting compounds and among them the 2-(4methoxyphenyl)-1,2,4-triazolo[1,5-alquinoxalin-4-one (8), which can be considered one of the most potent and selective hA(3) adenosine receptor antagonists reported till now. Moreover, as a new finding, replacement of the classical 2-(hetero)aryl moiety with a 2-carboxylate function (compounds 16-28 and 32-36) maintained good hA(3) AR binding activity but, most importantly and interestingly, produced a large increase in bA(3) versus hA(1) selectivity. A receptor-based SAR analysis provided new interesting insights about the steric and electrostatic requirements that are important for the anchoring of these derivatives at the hA(3) receptor recognition site, thus highlighting the versatility of the triazoloquinoxaline scaffold for obtaining potent and selective hA(3) AR antagonists.
• 4,5-Dihydro-1,2,4-triazolo[1,5-<i>a</i>]quinoxalin-4-ones:  Excitatory Amino Acid Antagonists with Combined Glycine/NMDA and AMPA Receptor Affinity
  作者：Daniela Catarzi、Vittoria Colotta、Flavia Varano、Lucia Cecchi、Guido Filacchioni、Alessandro Galli、Chiara Costagli

  DOI：10.1021/jm981102r

  日期：1999.7.1

  A series of 4,5-dihydro-1,2,4-triazolo[1,5-alpha]quinoxalin-4-ones bearing different substituents on the benzo-fused ring and at position 2 were synthesized and biologically evaluated for their binding at glycine/NMDA and AMPA receptors. Most of the reported compounds show combined glycine/NMDA and AMPA receptor binding activity providing further evidences of the structural similarities of the binding pockets of both receptor recognition sites. Moreover, this study has pointed out some differences for the binding at each receptor type. In particular, for the glycine/NMDA receptor-ligand interaction, the presence of a free acidic function at position 2 and an electron-withdrawing substituent(s) nonbulkier than chlorine atom(s) on the benzo-fused moiety is required. Functional antagonism at the NMDA receptor-ion channel complex was also performed on some selected compounds.