Benzoic acid,4-[[(4-amino-1,2-dihydro-1-oxo-2-phenyl[1,2,4]triazolo[4,3-a]quinoxalin-6-yl)amino]methyl]-, methyl ester | 660438-86-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: Benzoic acid,4-[[(4-amino-1,2-dihydro-1-oxo-2-phenyl[1,2,4]triazolo[4,3-a]quinoxalin-6-yl)amino]methyl]-, methyl ester
• CAS: 660438-86-8
• 化学式: C₂₄H₂₀N₆O₃
• 分子量: 440.461
• InChiKey: JIVFZKCTOKAARS-UHFFFAOYSA-N

物化性质

• 沸点：
  657.7±65.0 °C(Predicted)
• 密度：
  1.42±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.01
• 重原子数：
  33.0
• 可旋转键数：
  5.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  116.54
• 氢给体数：
  2.0
• 氢受体数：
  9.0

反应信息

• 作为反应物：
  描述：

  Benzoic acid,4-[[(4-amino-1,2-dihydro-1-oxo-2-phenyl[1,2,4]triazolo[4,3-a]quinoxalin-6-yl)amino]methyl]-, methyl ester 在 sodium hydroxide 作用下， 以 甲醇 为溶剂， 反应 3.0h， 以80%的产率得到
  参考文献：
  名称：

  Synthesis of 4-amino-6-(hetero)arylalkylamino-1,2,4-triazolo[4,3-a]quinoxalin-1-one derivatives as potent A2A adenosine receptor antagonists

  摘要：

  In previous papers (Colotta, V. et al. Arch. Pharm. Pharm. Med. Chem. 1999, 332, 39. Colotta, V. et al. J. Med. Chem. 2000, 43, 1158) we reported the synthesis and binding affinity at bovine (b) A(1) and A(2A) and human (h) A(3) adenosine receptors (ARs) of the 4-amino-6-benzylamino-2-phenyl-1,2,4-triazolo[4,3-a]quinoxalin-1-one (compound A) which resulted in a potent and selective A(2A) AR antagonist. Compound A provided the lead compound of a series of 6- or 8-(hetero)arylalkylamino-4-amino-2-phenyl- 1,2,4-triazolo[4,3-a]quinoxatin-1-one derivatives (compounds 1-20) which are the object of this paper. Most of the newly synthesized compounds are inactive at hA(3) ARs while they possess both nanomolar bA(2A) affinities and different degrees of bA(2A) versus bA(1) selectivity. The binding data show that hydrophilic substituents on the benzyl moiety are the most profitable for bA(2A) receptor affinity. Furthermore, their steric hindrance seems to play an important role for the bA(2A) AR interaction, thus suggesting that the 6-aralkylamino moiety of these ligands interacts with a size-limited binding pocket of this AR subtype. Thus, the SAR studies provided us some new insights about the structural requirements of the bA(2A) AR recognition site. (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2003.09.019
• 作为产物：
  描述：

  4-amino-1,2-dihydro-6-[(4-methoxyphenyl)methylene]amino-2-phenyl-1,2,4-triazolo[4,3-a]quinoxalin-1-one 在 sodium tetrahydroborate 、 三溴化硼 、 zinc(II) chloride 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 为溶剂， 反应 26.0h， 生成 Benzoic acid,4-[[(4-amino-1,2-dihydro-1-oxo-2-phenyl[1,2,4]triazolo[4,3-a]quinoxalin-6-yl)amino]methyl]-, methyl ester
  参考文献：
  名称：

  Synthesis of 4-amino-6-(hetero)arylalkylamino-1,2,4-triazolo[4,3-a]quinoxalin-1-one derivatives as potent A2A adenosine receptor antagonists

  摘要：

  In previous papers (Colotta, V. et al. Arch. Pharm. Pharm. Med. Chem. 1999, 332, 39. Colotta, V. et al. J. Med. Chem. 2000, 43, 1158) we reported the synthesis and binding affinity at bovine (b) A(1) and A(2A) and human (h) A(3) adenosine receptors (ARs) of the 4-amino-6-benzylamino-2-phenyl-1,2,4-triazolo[4,3-a]quinoxalin-1-one (compound A) which resulted in a potent and selective A(2A) AR antagonist. Compound A provided the lead compound of a series of 6- or 8-(hetero)arylalkylamino-4-amino-2-phenyl- 1,2,4-triazolo[4,3-a]quinoxatin-1-one derivatives (compounds 1-20) which are the object of this paper. Most of the newly synthesized compounds are inactive at hA(3) ARs while they possess both nanomolar bA(2A) affinities and different degrees of bA(2A) versus bA(1) selectivity. The binding data show that hydrophilic substituents on the benzyl moiety are the most profitable for bA(2A) receptor affinity. Furthermore, their steric hindrance seems to play an important role for the bA(2A) AR interaction, thus suggesting that the 6-aralkylamino moiety of these ligands interacts with a size-limited binding pocket of this AR subtype. Thus, the SAR studies provided us some new insights about the structural requirements of the bA(2A) AR recognition site. (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2003.09.019