4-Amino-2-phenyl-2H-[1,2,4]triazolo[4,3-a]quinoxalin-1-one | 269716-64-5

• 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-phenyl-2H-[1,2,4]triazolo[4,3-a]quinoxalin-1-one
• 英文别名: 4-amino-2-phenyl-[1,2,4]triazolo[4,3-a]quinoxalin-1-one
• CAS: 269716-64-5
• 化学式: C₁₅H₁₁N₅O
• 分子量: 277.285
• InChiKey: UNENFDNBTZLJMG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  21
• 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：
  74.3
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  二苯基乙酰氯 、 4-Amino-2-phenyl-2H-[1,2,4]triazolo[4,3-a]quinoxalin-1-one 在 吡啶 作用下， 以55%的产率得到N-(1-oxo-2-phenyl-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
• 作为产物：
  描述：

  2-Phenyl-2H,5H-[1,2,4]triazolo[4,3-a]quinoxaline-1,4-dione 在 吡啶 、 五氯化磷 、 氨 、 三氯氧磷 作用下， 以 乙醇 为溶剂， 生成 4-Amino-2-phenyl-2H-[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:  A Versatile Tool for the Synthesis of Potent and Selective Adenosine Receptor Antagonists

  摘要：

  4-Amino-6-benzylamino-1,2-dihydro-2-phenyl-1,2,4-triazolo[4,3-a]quinoxalin-1-one (1) has been found to be an A(2A) versus A(1) selective antagonist (Colotta et al. Arch. Pharm. Pharm. Med. Chem. 1999,332, 39-41). In this paper some novel triazoloquinoxalin-1-ones 4-25 bearing different substituents on the 2-phenyl and/or 4-amino moiety of the parent 4-amino-1,2-dihydro-2-phenyl-1,2,4-triazolo[4,3-a]quinoxalin-1-one (3) have been synthesized and tested in radioligand binding assays at bovine A(1) and A(2A) and cloned human A(3) adenosine receptors (AR). Moreover, the binding activities at the above-mentioned AR subtypes of the 1,4-dione parent compounds 26-31 and their 5-N-alkyl derivatives 33-37 were also evaluated. The substituent on the 2-phenyl ring exerted a different effect on AR subtypes, while replacement of a hydrogen atom of the 4-amino group with suitable substituents yielded selective A(1) or A(3) antagonists. Replacement of a hydrogen atom of the 4-NH2 with an acyl group, or replacement of the whole 4-NH2 with a 4-oxo moiety, shifted the binding activity toward the A(3) AR. The binding results allowed elucidation of the structural requirements for the binding of these novel tricyclic derivatives at each receptor subtype. In particular, A(1) and A(2A) binding required the presence of a proton donor group at position-4, while for A(3) affinity the presence of a proton acceptor in this same region was of paramount importance.

  DOI：

  10.1021/jm991096e

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.