4-amino-6-nitro-2-phenyl-2H-[1,2,4]triazolo[4,3-a]quinoxalin-1-one | 233675-50-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 4-amino-6-nitro-2-phenyl-2H-[1,2,4]triazolo[4,3-a]quinoxalin-1-one
• 英文别名: 4-amino-6-nitro-2-phenyl-1,2,4-triazolo[4,3-a]quinoxalin-1-one；4-amino-6-nitro-2-phenyl-[1,2,4]triazolo[4,3-a]quinoxalin-1-one
• CAS: 233675-50-8
• 化学式: C₁₅H₁₀N₆O₃
• 分子量: 322.283
• InChiKey: BZBZJCKGVWMYNE-UHFFFAOYSA-N

物化性质

• 熔点：
  290-291 °C(Solv: tetrahydrofuran (109-99-9); water (7732-18-5))
• 沸点：
  552.0±52.0 °C(Predicted)
• 密度：
  1.69±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  24
• 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：
  120
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  4-amino-6-nitro-2-phenyl-2H-[1,2,4]triazolo[4,3-a]quinoxalin-1-one 在 三乙胺 、 tin(ll) chloride 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 反应 2.33h， 生成 N-(4-amino-1-oxo-2-phenyl-1,2-dihydro-[1,2,4]triazolo[4,3-a]quinoxalin-6-yl)-2,2,2-trifluoroacetamide
  参考文献：
  名称：

  4,6-二氨基-1,2-二氢-2-苯基-1,2,4-三唑并[4,3-a]喹喔啉-2H-1-one的衍生物：潜在的拮抗剂配体，可通过以下方式成像A2A腺苷受体正电子发射断层扫描（PET）。

  摘要：

  脑A2A腺苷受体（A（2A）AR）在运动障碍中的重要性促使开发通过正电子发射断层扫描（PET）对这些受体成像的放射性标记配体。这项研究评估了一类A（2A）AR拮抗剂，即4-氨基-6-苄氨基-1,2-二氢-2-苯基-1,2,4-三唑[4,3-a]喹喔啉-2H的衍生物-1-o ne，10a，作为通过PET对大脑A（2A）ARs进行成像的试剂。对10a文献合成的修改有效地产生了用于药理学评估的类似物10b-s。放射性配体结合实验显示出在低纳摩尔范围内对大鼠脑A（2A）AR的亲和力，但对A1AR的亲和力和基本的非特异性结合却很相似。使用[3H] 10a的放射自显影显示高的非特异性结合使对A1AR和A（2A）AR的特异性结合变得模糊。因此，

  DOI：

  10.1016/j.ejmech.2004.12.005
• 作为产物：
  描述：

  ethyl (phenylhydrazono)chloroacetate 在 五氯化磷 、 氨 、 三乙胺 、 三氯氧磷 作用下， 以 四氢呋喃 、 吡啶 、 乙醇 为溶剂， 生成 4-amino-6-nitro-2-phenyl-2H-[1,2,4]triazolo[4,3-a]quinoxalin-1-one
  参考文献：
  名称：

  4-Amino-6-benzylamino-1,2-dihydro-2-phenyl-1,2,4-triazolo[4,3-α]-quinoxalin-1-one: A New A2A Adenosine Receptor Antagonist with High Selectivity versus A1 Receptors

  摘要：

  DOI：

  10.1002/(sici)1521-4184(19993)332:2<39::aid-ardp39>3.3.co;2-6

文献信息

• Synthesis, ligand–receptor modeling studies and pharmacological evaluation of novel 4-modified-2-aryl-1,2,4-triazolo[4,3-a]quinoxalin-1-one derivatives as potent and selective human A3 adenosine receptor antagonists
  作者：Vittoria Colotta、Daniela Catarzi、Flavia Varano、Ombretta Lenzi、Guido Filacchioni、Claudia Martini、Letizia Trincavelli、Osele Ciampi、Chiara Traini、Anna Maria Pugliese、Felicita Pedata、Erika Morizzo、Stefano Moro

  DOI：10.1016/j.bmc.2008.04.039

  日期：2008.6

  The study of some 4-substituted-2-aryl-1,2,4-triazolo[4,3-a]quinoxalin-1-one derivatives, designed as hA(3) adenosine receptor antagonists, is reported. The new compounds bear on the four-position different acylamino, sulfonylamino, benzylureido and benzyloxy moieties, which have also been combined with a para-methoxy group on the 2-phenyl ring or with a nitro residue at the six-position. Many derivatives show high hA(3) adenosine receptor affinities and selectivities both versus hA(1) and hA(2A) receptors. The observed structure-affinity relationships of this class of antagonists have been exhaustively rationalized using the recently published ligand-based homology modeling (LBHM) approach. The selected 4-bismethanesulfonylamino-2-phenyl-1,2,4-triazolo[4,3a]quinoxalin-1-one (13), which shows high hA(3) affinity (K-i = 5.5 nM) and selectivity versus hA(1), hA(2A) (both selectivity ratios > 1800) and hA(2B) (cAMP assay, IC50 > 10,000 nM) receptors, was tested in an in vitro rat model of cerebral ischemia, proving to be effective in preventing the failure of synaptic activity, induced by oxygen and glucose deprivation in the hippocampus, and in delaying the occurrence of anoxic depolarization. (C) 2008 Elsevier Ltd. All rights reserved.
• 4-Amido-2-aryl-1,2,4-triazolo[4,3-<i>a</i>]quinoxalin-1-ones as New Potent and Selective Human A₃ Adenosine Receptor Antagonists. Synthesis, Pharmacological Evaluation, and Ligand−Receptor Modeling Studies
  作者：Ombretta Lenzi、Vittoria Colotta、Daniela Catarzi、Flavia Varano、Guido Filacchioni、Claudia Martini、Letizia Trincavelli、Osele Ciampi、Katia Varani、Federico Marighetti、Erika Morizzo、Stefano Moro

  DOI：10.1021/jm060373w

  日期：2006.6.1

  A structural investigation on some 4-amido-2-phenyl-1,2-dihydro-1,2,4-triazolo[ 4,3-a] quinoxalin-1-one derivatives, designed as human A(3) adenosine receptor ( hA(3) AR) antagonists, is described. In the new derivatives, some acyl residues with different steric bulk were introduced on the 4-amino group, and their combination with the 4-methoxy group on the 2-phenyl moiety, and/or the 6-nitro/6-amino substituent on the fused benzo ring, was also evaluated. Most of the new derivatives were potent and selective hA(3) AR antagonists. SAR analysis showed that hindering and lipophilic acyl moieties not only are well tolerated but even ameliorate the hA(3) affinity. Interestingly, the 4-methoxy substituent on the appended 2-phenyl moiety, as well as the 6-amino group, always exerted a positive effect, shifting the affinity toward the hA(3) receptor subtype. In contrast, the 6-nitro substituent exerted a variable effect. An intensive molecular modeling investigation was performed to rationalize the experimental SAR findings.
• Derivatives of 4,6-diamino-1,2-dihydro-2-phenyl-1,2,4-triazolo[4,3-a]quinoxalin-2H-1-one: potential antagonist ligands for imaging the A2A adenosine receptor by positron emission tomography (PET)
  作者：Marcus H. Holschbach、Dirk Bier、Walter Wutz、Wiebke Sihver、M. Schüller、Ray A. Olsson

  DOI：10.1016/j.ejmech.2004.12.005

  日期：2005.5

  in movement disorders urges the development of radiolabeled ligands for imaging those receptors by positron emission tomography (PET). This study evaluated one class of A(2A)AR antagonists, derivatives of 4-amino-6-benzylamino-1,2-dihydro-2-phenyl-1,2,4-triazolo[4,3-a]quinoxalin-2H-1-o ne, 10a, as agents for imaging brain A(2A)ARs by PET.. Modifications of a literature synthesis of 10a efficiently

  脑A2A腺苷受体（A（2A）AR）在运动障碍中的重要性促使开发通过正电子发射断层扫描（PET）对这些受体成像的放射性标记配体。这项研究评估了一类A（2A）AR拮抗剂，即4-氨基-6-苄氨基-1,2-二氢-2-苯基-1,2,4-三唑[4,3-a]喹喔啉-2H的衍生物-1-o ne，10a，作为通过PET对大脑A（2A）ARs进行成像的试剂。对10a文献合成的修改有效地产生了用于药理学评估的类似物10b-s。放射性配体结合实验显示出在低纳摩尔范围内对大鼠脑A（2A）AR的亲和力，但对A1AR的亲和力和基本的非特异性结合却很相似。使用[3H] 10a的放射自显影显示高的非特异性结合使对A1AR和A（2A）AR的特异性结合变得模糊。因此，
• 4-Amino-6-benzylamino-1,2-dihydro-2-phenyl-1,2,4-triazolo[4,3-α]-quinoxalin-1-one: A New A2A Adenosine Receptor Antagonist with High Selectivity versus A1 Receptors
  作者：Vittoria Colotta、Daniela Catarzi、Flavia Varano、Lucia Cecchi、Guido Filacchioni、Claudia Martini、Letizia Trincavelli、Antonio Lucacchini

  DOI：10.1002/(sici)1521-4184(19993)332:2<39::aid-ardp39>3.3.co;2-6

  日期：1999.3