8-methylpyrazolo<5,1-c><1,2,4>benzotriazine 5-oxide | 177158-49-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 三嗪类
• 英文名称: 8-methylpyrazolo<5,1-c><1,2,4>benzotriazine 5-oxide
• 英文别名: 8-methylpyrazolo[5,1-c][1,2,4]-benzotriazine 5-oxide；8-Methyl-5-oxidopyrazolo[5,1-c][1,2,4]benzotriazin-5-ium
• CAS: 177158-49-5
• 化学式: C₁₀H₈N₄O
• 分子量: 200.2
• InChiKey: MOUZZUYJQJPDAU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  15
• 可旋转键数：
  0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  55.6
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  8-methylpyrazolo<5,1-c><1,2,4>benzotriazine 5-oxide 在 一氯化碘 作用下， 以 氯仿 为溶剂， 以62%的产率得到3-iodo-8-methylpyrazolo[5,1-c][1,2,4]-benzotriazine 5-oxide
  参考文献：
  名称：

  苯二氮杂receptor受体配体。图8：新的吡唑并[5，1-c] [1,2,4]苯并三嗪5-氧化物3-和8-二取代的合成和药理学评价：具有反向激动剂药理学功效的高亲和力配体。

  摘要：

  报道了新的3-芳基酯和3-杂芳基吡唑并[5,1-c] [1,2,4]苯并三嗪5-氧化物8-取代的合成和结合研究。这些取代基的性质（就亲脂性和电子特性而言）似乎会影响结合亲和力。研究了体内高亲和力配体的药理作用，其中考虑了六种潜在的苯二氮卓类作用：抗焦虑作用，肌肉松弛作用，运动协调，抗惊厥作用，自发运动和乙醇增强作用。化合物4d和6d显示出反向激动剂特征。还评估了这些化合物在GABAA受体复合物（GABAA / BzR复合物）亚型上苯并二氮杂位处的结合，以评估其亚型选择性。

  DOI：

  10.1016/j.bmc.2005.08.058
• 作为产物：
  描述：

  1-(2-nitro-5-methylphenyl)-5-aminopyrazole 在 sodium hydroxide 作用下， 反应 24.0h， 以85%的产率得到8-methylpyrazolo<5,1-c><1,2,4>benzotriazine 5-oxide
  参考文献：
  名称：

  Benzodiazepine receptor ligands. Synthesis and pharmacological evaluation of 3-, 7- and 8-substituted [5,1-c][1,2,4]benzotriazines and 5-oxide derivatives. Part I

  摘要：

  A new series of 3-, 7- and 8-substituted pyrazolo[5,1-c][1,2,4]benzotriazine 5-oxides and a series of pyrazolo[5,1-c][1,2,4]benzotriazines were synthesized and their benzodiazepine receptor affinities were evaluated in vitro. A study of structure-affinity relationships within the series is briefly discussed, considering the role of various substituents at the 3-, 7- and 8-positions and the role of N-5-oxide. Compounds 1b, 1c, 1cR, 4c, 4cR, 9d, 12d and 12dR were evaluated in vivo for their anticonvulsant effects.

  DOI：

  10.1016/0223-5234(96)80363-1

文献信息

• Novel 3-iodo-8-ethoxypyrazolo[5,1-c][1,2,4]benzotriazine 5-oxide as promising lead for design of α5-inverse agonist useful tools for therapy of mnemonic damage
  作者：Gabriella Guerrini、Giovanna Ciciani、Giovanni Cambi、Fabrizio Bruni、Silvia Selleri、François Besnard、Marina Montali、Claudia Martini、Carla Ghelardini、Nicoletta Galeotti、Annarella Costanzo

  DOI：10.1016/j.bmc.2007.01.053

  日期：2007.4

  binding study of new 3-iodiopyrazolo[5,1-c][1,2,4] benzotriazine 5-oxides 8-alkyloxy substituted are reported. The replacement at position 3 with an iodine atom, with respect to substituents capable to form a three centered hydrogen bond and/or to form pi-pi stacking interaction with receptor protein, gave high affinity ligands, independently of the 8-alkyloxy substituent. High-affinity ligands were studied

  报道了新的3-碘吡唑并[5,1-c] [1,2,4]苯并三嗪5-氧化物被8-烷氧基取代的合成及结合研究。相对于能够形成三个中心氢键和/或与受体蛋白形成π-π堆积相互作用的取代基，在3位用碘原子取代，得到了高亲和力的配体，而与8-烷氧基取代基无关。研究了体内高亲和力配体的药理作用，其中考虑了五种潜在的苯二氮卓类作用：抗焦虑作用，运动协调，抗惊厥作用，小鼠学习和记忆障碍以及乙醇增强作用。化合物5c和5'c具有相反的激动剂分布，并且首次被证明是促记忆的。
• Benzodiazepine receptor ligands. 8: Synthesis and pharmacological evaluation of new pyrazolo[5,1-c] [1,2,4]benzotriazine 5-oxide 3- and 8-disubstituted: High affinity ligands endowed with inverse-agonist pharmacological efficacy
  作者：Gabriella Guerrini、Annarella Costanzo、Giovanna Ciciani、Fabrizio Bruni、Silvia Selleri、Camilla Costagli、François Besnard、Barbara Costa、Claudia Martini、Gaetano De Siena、Petra Malmberg-Aiello

  DOI：10.1016/j.bmc.2005.08.058

  日期：2006.2

  The synthesis and the binding study of new 3-arylesters and 3-heteroarylpyrazolo[5,1-c][1,2,4]benzotriazine 5-oxide 8-substituted are reported. The nature of these substituents (in terms of lipophilic and electronic features) seems to influence the binding affinity. High-affinity ligands were studied in mice in vivo for their pharmacological effects, considering six potential benzodiazepine actions:

  报道了新的3-芳基酯和3-杂芳基吡唑并[5,1-c] [1,2,4]苯并三嗪5-氧化物8-取代的合成和结合研究。这些取代基的性质（就亲脂性和电子特性而言）似乎会影响结合亲和力。研究了体内高亲和力配体的药理作用，其中考虑了六种潜在的苯二氮卓类作用：抗焦虑作用，肌肉松弛作用，运动协调，抗惊厥作用，自发运动和乙醇增强作用。化合物4d和6d显示出反向激动剂特征。还评估了这些化合物在GABAA受体复合物（GABAA / BzR复合物）亚型上苯并二氮杂位处的结合，以评估其亚型选择性。
• Benzodiazepine receptor ligands. Synthesis and pharmacological evaluation of 3-, 7- and 8-substituted [5,1-c][1,2,4]benzotriazines and 5-oxide derivatives. Part I
  作者：G Guerrini、A Costanzo、F Bruni、S Selleri、L Casilli、L Giusti、C Martini、A Lucacchini、P Malmberg Aiello、A Ipponi

  DOI：10.1016/0223-5234(96)80363-1

  日期：1996.1

  A new series of 3-, 7- and 8-substituted pyrazolo[5,1-c][1,2,4]benzotriazine 5-oxides and a series of pyrazolo[5,1-c][1,2,4]benzotriazines were synthesized and their benzodiazepine receptor affinities were evaluated in vitro. A study of structure-affinity relationships within the series is briefly discussed, considering the role of various substituents at the 3-, 7- and 8-positions and the role of N-5-oxide. Compounds 1b, 1c, 1cR, 4c, 4cR, 9d, 12d and 12dR were evaluated in vivo for their anticonvulsant effects.