9-bromo-2-phenyl-5-(methylsulfanyl)[1,2,4]triazolo[4,3-c]-quinazolin-3(2H)-one | 1189797-85-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 9-bromo-2-phenyl-5-(methylsulfanyl)[1,2,4]triazolo[4,3-c]-quinazolin-3(2H)-one
• 英文别名: 9-Bromo-5-methylsulfanyl-2-phenyl-[1,2,4]triazolo[4,3-c]quinazolin-3-one
• CAS: 1189797-85-0
• 化学式: C₁₆H₁₁BrN₄OS
• 分子量: 387.26
• InChiKey: HDQOAGZTGPNXFJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  23
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  73.6
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  9-bromo-2-phenyl-5-(methylsulfanyl)[1,2,4]triazolo[4,3-c]-quinazolin-3(2H)-one 在 间氯过氧苯甲酸 作用下， 以 二氯甲烷 为溶剂， 反应 6.0h， 以100%的产率得到9-bromo-2-phenyl-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
• 作为产物：
  描述：

  6-溴-4-氯-2-(甲基磺酰基)喹唑啉 、 乙基1-苯基肼羧酸酯 在 N,N-二异丙基乙胺 作用下， 反应 60.0h， 以71%的产率得到9-bromo-2-phenyl-5-(methylsulfanyl)[1,2,4]triazolo[4,3-c]-quinazolin-3(2H)-one
  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

• [EN] GABAa RECEPTOR MODULATORS<br/>[FR] MODULATEURS DES RÉCEPTEURS GABAA
  申请人：FORSKARPATENT I SYD AB

  公开号：WO2009123537A1

  公开（公告）日：2009-10-08

  the resent invention relates to novel compounds of the general formula (I) having anxiolytic, anticonvulsant, sedative-hypnotic and myorelaxant conditions as well as anxiogenic, somnolytic and convulsant conditions in mammals, including humans, as GABAA receptor modulator.

  这项最新的发明涉及具有广谱公式(I)的新化合物，具有镇静、抗惊厥、催眠-催眠和肌肉松弛条件，以及作为GABAA受体调节剂的哺乳动物，包括人类，具有焦虑、催眠和癫痫症状。
• GABAA RECEPTOR MODULATORS
  申请人：Nielsen Mogens

  公开号：US20110092525A1

  公开（公告）日：2011-04-21

  The resent invention relates to novel compounds of the general formula (I) having anxiolytic, anticonvulsant, sedative-hypnotic and myorelaxant conditions as well as anxiogenic, somnolytic and convulsant conditions in mammals, including humans, as GABA A receptor modulator.

  本发明涉及具有广泛公式（I）的新化合物，作为GABAA受体调节剂在哺乳动物，包括人类中具有抗焦虑，抗惊厥，镇静催眠和肌肉松弛条件，以及焦虑，催眠和惊厥条件。
• US8809355B2
  申请人：——

  公开号：US8809355B2

  公开（公告）日：2014-08-19
• 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.