[1,2,4]三唑并[1,5-a]喹喔啉-4(5H)-酮,2-苯基- | 155951-49-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 中文名称: [1,2,4]三唑并[1,5-a]喹喔啉-4(5H)-酮,2-苯基-
• 英文名称: 4,5-dihydro-2-phenyl-1,2,4-triazolo<1,5-a>quinoxalin-4-one
• 英文别名: 2-phenyl-[1,2,4]triazolo[1,5-a]quinoxalin-4(5H)-one；2-phenyl-5H-[1,2,4]triazolo[1,5-a]quinoxalin-4-one
• CAS: 155951-49-8
• 化学式: C₁₅H₁₀N₄O
• 分子量: 262.271
• InChiKey: OZBRJYNXLLCKFI-UHFFFAOYSA-N

物化性质

• 密度：
  1.43±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  20
• 可旋转键数：
  1
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  59.8
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  [1,2,4]三唑并[1,5-a]喹喔啉-4(5H)-酮,2-苯基- 在 lithium aluminium tetrahydride 、 溶剂黄146 作用下， 以 四氢呋喃 为溶剂， 反应 5.0h， 生成 2-phenyl-1,2,4-triazolo<1,5-a>quinoxaline
  参考文献：
  名称：

  1,2,4-Triazolo[1,5-a]quinoxaline derivatives and their simplified analogues as adenosine A3 receptor antagonists. Synthesis, structure–affinity relationships and molecular modeling studies

  摘要：

  The 1,2,4-triazolo[1,5-a]quinoxaline (TQX) scaffold was extensively investigated in our previously reported studies and recently, our attention was focused at position 5 of the tricyclic nucleus where different acyl and carboxylate moieties were introduced (compounds 2-15). This study produced some interesting compounds endowed with good hA(3) receptor affinity and selectivity. In addition, to find new insights about the structural requirements for hA(3) receptor-ligand interaction, the tricyclic TQX ring was destroyed yielding some 1,2,4-triazole derivatives (compounds 16-23). These simplified compounds, though maintaining the crucial structural requirements for adenosine receptor-ligand interaction, have a very low hA(3) adenosine receptor affinity, the only exception being compound 23 (1-[3-(4-methoxyphenyl)-1-phenyl-1H-1,2,4-triazol-5-yl]-3-phenylurea) endowed with a K-i value in the micro-molar range and high hA(3) selectivity versus both hA(1) and hA(2A) AR subtypes. Evaluation of the side products obtained in the herein reported synthetic pathways led to the identification of some new triazolo[1,5-a]quinoxalines as hA(3)AR antagonists (compounds 24-27). These derivatives, though lacking the classical structural requirements for the anchoring at the hA(3) receptor site, show high hA(3) affinity and in some case selectivity versus hA(1) and hA(2A) subtypes. Molecular docking of the herein reported tricyclic and simplified derivatives was carried out to depict their hypothetical binding mode to our model of hA(3) receptor. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2014.11.033
• 作为产物：
  描述：

  ethyl 1-(2-nitrophenyl)-3-phenyl-1,2,4-triazole-5-carboxylate 在 铁粉 、 溶剂黄146 作用下， 以60%的产率得到[1,2,4]三唑并[1,5-a]喹喔啉-4(5H)-酮,2-苯基-
  参考文献：
  名称：

  Catarzi; Cecchi; Colotta, Il Farmaco, 1993, vol. 48, # 8, p. 1065 - 1078

  摘要：

  DOI：

文献信息

• 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.
• Synthesis of some tricyclic heteroaromatic systems and their A1 and A2a adenosine binding activity
  作者：V Colotta、L Cecchi、D Catarzi、G Filacchioni、C Martini、P Tacchi、A Lucacchini

  DOI：10.1016/0223-5234(96)88218-3

  日期：1995.1

  The syntheses, A(1) and A(2a) adenosine receptor affinities and structure-activity relationships of some 2-aryl-1,2,4-triazolo[1,5-a]quinoxalines, 2-arylimidazo[1,2-a]quinoxalines, 1-arylimidazo[1,5-a]quinoxalines are reported and compared with that of a previously reported 2-phenylpyrazolo[1,5-a]quinoxaline. The results show that some triazoloquinoxalines are potent and specific A(1) adenosine receptor ligands and that the replacement of either nitrogen at position 1 or 3 of the triazoloquinoxaline moiety with a CH brought about a decrease in affinity at both adenosine receptors.
• Catarzi; Cecchi; Colotta, Il Farmaco, 1993, vol. 48, # 8, p. 1065 - 1078
  作者：Catarzi、Cecchi、Colotta、Melani、Filacchioni、Martini、Giusti、Lucacchini

  DOI：——

  日期：——
• 1,2,4-Triazolo[1,5-a]quinoxaline derivatives and their simplified analogues as adenosine A3 receptor antagonists. Synthesis, structure–affinity relationships and molecular modeling studies
  作者：Daniela Catarzi、Flavia Varano、Daniela Poli、Lucia Squarcialupi、Marco Betti、Letizia Trincavelli、Claudia Martini、Diego Dal Ben、Ajiroghene Thomas、Rosaria Volpini、Vittoria Colotta

  DOI：10.1016/j.bmc.2014.11.033

  日期：2015.1

  The 1,2,4-triazolo[1,5-a]quinoxaline (TQX) scaffold was extensively investigated in our previously reported studies and recently, our attention was focused at position 5 of the tricyclic nucleus where different acyl and carboxylate moieties were introduced (compounds 2-15). This study produced some interesting compounds endowed with good hA(3) receptor affinity and selectivity. In addition, to find new insights about the structural requirements for hA(3) receptor-ligand interaction, the tricyclic TQX ring was destroyed yielding some 1,2,4-triazole derivatives (compounds 16-23). These simplified compounds, though maintaining the crucial structural requirements for adenosine receptor-ligand interaction, have a very low hA(3) adenosine receptor affinity, the only exception being compound 23 (1-[3-(4-methoxyphenyl)-1-phenyl-1H-1,2,4-triazol-5-yl]-3-phenylurea) endowed with a K-i value in the micro-molar range and high hA(3) selectivity versus both hA(1) and hA(2A) AR subtypes. Evaluation of the side products obtained in the herein reported synthetic pathways led to the identification of some new triazolo[1,5-a]quinoxalines as hA(3)AR antagonists (compounds 24-27). These derivatives, though lacking the classical structural requirements for the anchoring at the hA(3) receptor site, show high hA(3) affinity and in some case selectivity versus hA(1) and hA(2A) subtypes. Molecular docking of the herein reported tricyclic and simplified derivatives was carried out to depict their hypothetical binding mode to our model of hA(3) receptor. (C) 2014 Elsevier Ltd. All rights reserved.