4-amino-2-(4-methoxyphenyl)-6-nitro-1,2,4-triazolo[4,3-a]quinoxalin-1-one | 733746-29-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 4-amino-2-(4-methoxyphenyl)-6-nitro-1,2,4-triazolo[4,3-a]quinoxalin-1-one
• 英文别名: 4-amino-2-(4-methoxyphenyl)-6-nitro-[1,2,4]triazolo[4,3-a]quinoxalin-1(2H)-one；4-amino-2-(4-methoxyphenyl)-6-nitro-[1,2,4]triazolo[4,3-a]quinoxalin-1-one
• CAS: 733746-29-7
• 化学式: C₁₆H₁₂N₆O₄
• 分子量: 352.309
• InChiKey: JCIPMVJKIINWMG-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：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  129
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  4-amino-2-(4-methoxyphenyl)-6-nitro-1,2,4-triazolo[4,3-a]quinoxalin-1-one 在 palladium on activated charcoal 吡啶 、 氢气 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 12.0h， 生成 6-Amino-1,2-dihydro-2-(methoxyphenyl)-4-diphenylacetamido-1,2,4-triazolo[4,3-a]quinoxalin-1-one
  参考文献：
  名称：

  4-Amido-2-aryl-1,2,4-triazolo[4,3-a]quinoxalin-1-ones as New Potent and Selective Human A₃ Adenosine Receptor Antagonists. Synthesis, Pharmacological Evaluation, and Ligand−Receptor Modeling Studies

  摘要：

  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.

  DOI：

  10.1021/jm060373w
• 作为产物：
  描述：

  [(4-甲氧基苯基)肼基]氯乙酸乙酯 在 吡啶 、 五氯化磷 、 氨 、 三乙胺 、 三氯氧磷 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 反应 3.0h， 生成 4-amino-2-(4-methoxyphenyl)-6-nitro-1,2,4-triazolo[4,3-a]quinoxalin-1-one
  参考文献：
  名称：

  1,2,4-Triazolo[4,3-a]quinoxalin-1-one Moiety as an Attractive Scaffold To Develop New Potent and Selective Human A₃ Adenosine Receptor Antagonists:  Synthesis, Pharmacological, and Ligand−Receptor Modeling Studies

  摘要：

  In the past few years much effort in our laboratory has been directed toward the study of adenosine receptor antagonists, and recently we focused our attention on 2-aryl-1,2,4-triazolo[4,3-a]quinoxaline-1,4-diones and 2-aryl-1,2,4-triazolo [4,3-a]quinoxalin-4-amino-1-ones, some of which were potent and/or selective A(3) receptor antagonists. In the present paper, a new series of triazoloquinoxaline derivatives is described. Most of the new compounds, biologically evaluated in radioligand binding assays at bovine (b) A(1) and A(2A) and at human (h) A(1) and A(3) adenosine receptors, showed high hA(3) adenosine receptor affinity and selectivity. In particular, 2-(4-nitrophenyl)-1,2,4,5-tetrahydro-1,2,4-triazolo[4,3-a]quinoxaline-1,4-dione (1), also tested at the hA(2A) ARs, shows the best binding profile with a high hA(3) affinity (K-i = 0.60 nM) and strong selectivity vs hA(1) and vs hA(2A) receptors (both selectivity ratios greater than 16 600). To interpret our experimental results, we decided to theoretically depict the putative transmembrane binding motif of our triazoloquinoxaline analogues on hA(3) receptor. Structure-activity relationships have been explained analyzing the three-dimensional structure of the antagonist-receptor models obtained by molecular docking simulation.

  DOI：

  10.1021/jm031136l