4-Amino-6-(4-methoxy-benzylamino)-2-phenyl-2H-[1,2,4]triazolo[4,3-a]quinoxalin-1-one | 660438-82-4

• 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-(4-methoxy-benzylamino)-2-phenyl-2H-[1,2,4]triazolo[4,3-a]quinoxalin-1-one
• CAS: 660438-82-4
• 化学式: C₂₃H₂₀N₆O₂
• 分子量: 412.451
• InChiKey: XYBFHZLWOSIISI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.24
• 重原子数：
  31.0
• 可旋转键数：
  5.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  99.47
• 氢给体数：
  2.0
• 氢受体数：
  8.0

反应信息

• 作为反应物：
  描述：

  4-Amino-6-(4-methoxy-benzylamino)-2-phenyl-2H-[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
  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：

  4,6-Diamino-2-phenyl-2H-[1,2,4]triazolo[4,3-a]quinoxalin-1-one 在 sodium tetrahydroborate 、 zinc(II) chloride 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 生成 4-Amino-6-(4-methoxy-benzylamino)-2-phenyl-2H-[1,2,4]triazolo[4,3-a]quinoxalin-1-one
  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

文献信息

• 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，