9-[2-(biphenyl-4-yl)ethyl]-2-(4-methylphenyl)-2,6-dihydro[1,2,4]triazolo[4,3-c]-quinazoline-3,5-dione | 1189797-74-7

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 二苯乙烯类
• 英文名称: 9-[2-(biphenyl-4-yl)ethyl]-2-(4-methylphenyl)-2,6-dihydro[1,2,4]triazolo[4,3-c]-quinazoline-3,5-dione
• 英文别名: 9-[2-(biphen-4-yl)ethyl]-2-(4-methylphenyl)-2,6-dihydro[1,2,4]triazolo[4,3-c]-quinazoline-3,5-dione；2-(4-methylphenyl)-9-[2-(4-phenylphenyl)ethyl]-6H-[1,2,4]triazolo[4,3-c]quinazoline-3,5-dione
• CAS: 1189797-74-7
• 化学式: C₃₀H₂₄N₄O₂
• 分子量: 472.546
• InChiKey: ADPAIMPXYZVGII-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.2
• 重原子数：
  36
• 可旋转键数：
  5
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  65
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  9-(biphenyl-4-ylethynyl)-2-(4-methylphenyl)-2,6-dihydro-[1,2,4]triazolo[4,3-c]-quinazoline-3,5-dione 在 palladium 10% on activated carbon 、 氢气 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 20.0 ℃ 、101.33 kPa 条件下， 反应 12.0h， 以98%的产率得到9-[2-(biphenyl-4-yl)ethyl]-2-(4-methylphenyl)-2,6-dihydro[1,2,4]triazolo[4,3-c]-quinazoline-3,5-dione
  参考文献：
  名称：

  Triazoloquinazolinediones as novel high affinity ligands for the benzodiazepine site of GABAA receptors

  摘要：

  Based on a pharmacophore model of the benzodiazepine-binding site of GABA(A) receptors, a series of 2-aryl-2,6-dihydro[1,2,4]triazolo[4,3-c]quinazoline-3,5-diones (structure type I) were designed, synthesized, and identified as high-affinity ligands of the binding site. For several compounds, K-i values of around 0.20 nM were determined. They show a structural resemblance with the previously described 2-phenyl-2H-pyrazolo[4,3-c]quinolin-3(5H)-ones (II) and 2-phenyl-[1,2,4]triazolo[1,5-a]quinoxalin-4(5H)-one (III). The 9-bromo substituted compounds 8a-d were prepared in an 8-step synthesis in an overall yield of approximately 40%, and a library of 9-substituted analogues was prepared by cross-coupling reactions. Compound 8e, 21, 22, and 24 were tested on recombinant rat alpha(1)beta(3)gamma(2), alpha(2)beta(3)gamma(2), alpha(3)beta(3)gamma(2), and alpha(5)beta(3)gamma(2) subtypes, and displayed selectivity for the alpha(1)beta(3)gamma(2) isoform. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2010.11.050

文献信息

• Triazoloquinazolinediones as novel high affinity ligands for the benzodiazepine site of GABAA receptors
  作者：Jakob Nilsson、Ritha Gidlöf、Elsebet Østergaard Nielsen、Tommy Liljefors、Mogens Nielsen、Olov Sterner

  DOI：10.1016/j.bmc.2010.11.050

  日期：2011.1

  Based on a pharmacophore model of the benzodiazepine-binding site of GABA(A) receptors, a series of 2-aryl-2,6-dihydro[1,2,4]triazolo[4,3-c]quinazoline-3,5-diones (structure type I) were designed, synthesized, and identified as high-affinity ligands of the binding site. For several compounds, K-i values of around 0.20 nM were determined. They show a structural resemblance with the previously described 2-phenyl-2H-pyrazolo[4,3-c]quinolin-3(5H)-ones (II) and 2-phenyl-[1,2,4]triazolo[1,5-a]quinoxalin-4(5H)-one (III). The 9-bromo substituted compounds 8a-d were prepared in an 8-step synthesis in an overall yield of approximately 40%, and a library of 9-substituted analogues was prepared by cross-coupling reactions. Compound 8e, 21, 22, and 24 were tested on recombinant rat alpha(1)beta(3)gamma(2), alpha(2)beta(3)gamma(2), alpha(3)beta(3)gamma(2), and alpha(5)beta(3)gamma(2) subtypes, and displayed selectivity for the alpha(1)beta(3)gamma(2) isoform. (C) 2010 Elsevier Ltd. All rights reserved.