N-(2-(4-methoxyphenyl)-6-nitro-1-oxo-1,2-dihydro-[1,2,4]triazolo[4,3-a]quinoxalin-4-yl)-2,2-diphenylacetamide

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: N-(2-(4-methoxyphenyl)-6-nitro-1-oxo-1,2-dihydro-[1,2,4]triazolo[4,3-a]quinoxalin-4-yl)-2,2-diphenylacetamide
• 英文别名: N-[2-(4-methoxyphenyl)-6-nitro-1-oxo-[1,2,4]triazolo[4,3-a]quinoxalin-4-yl]-2,2-diphenylacetamide
• 化学式: C₃₀H₂₂N₆O₅
• 分子量: 546.542
• InChiKey: NYQXAUGPKPPXNS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5
• 重原子数：
  41
• 可旋转键数：
  6
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  132
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  N-(2-(4-methoxyphenyl)-6-nitro-1-oxo-1,2-dihydro-[1,2,4]triazolo[4,3-a]quinoxalin-4-yl)-2,2-diphenylacetamide 在 palladium on activated charcoal 氢气 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 12.0h， 以65%的产率得到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：

  二苯基乙酰氯 、 4-amino-2-(4-methoxyphenyl)-6-nitro-1,2,4-triazolo[4,3-a]quinoxalin-1-one 在 吡啶 作用下， 以98%的产率得到N-(2-(4-methoxyphenyl)-6-nitro-1-oxo-1,2-dihydro-[1,2,4]triazolo[4,3-a]quinoxalin-4-yl)-2,2-diphenylacetamide
  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

文献信息

• 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.