8-ethoxypyrazolo[5,1-c][1,2,4]-benzotriazine 5-oxide | 161464-48-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 8-ethoxypyrazolo[5,1-c][1,2,4]-benzotriazine 5-oxide
• 英文别名: 8-Ethoxy-5-oxidopyrazolo[5,1-c][1,2,4]benzotriazin-5-ium
• CAS: 161464-48-8
• 化学式: C₁₁H₁₀N₄O₂
• 分子量: 230.226
• InChiKey: WJTPADAUNYWPAF-UHFFFAOYSA-N

物化性质

• 沸点：
  284.0±45.0 °C(Predicted)
• 密度：
  1.45±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  17
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  64.9
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  8-ethoxypyrazolo[5,1-c][1,2,4]-benzotriazine 5-oxide 在 盐酸 、 双氧水 、 锌 作用下， 以 乙酸酐 、 溶剂黄146 为溶剂， 生成 6-Ethoxy-1-oxy-4H-benzo[1,2,4]triazin-3-one
  参考文献：
  名称：

  Benzodiazepine receptor ligands — Part II. Synthesis and biological evaluation of pyrazolo[5,1-c][1,2,4]benzotriazine 4-oxide

  摘要：

  A new series of 3-, 8-substituted pyrazolo[5,1-c][1,2,4]benzotriazine 4-oxides 3 were synthesized and their benzodiazepine receptor (BZR) affinities were evaluated in vitro in comparison with their 5-oxide isomers 2. The 4-oxide compounds 3c,m,n,o showed a better receptor affinity than their corresponding 5-oxide isomers, with an efficacy trend of antagonist/partial inverse agonist. From a structure-affinity relationship point of view some insight in the role played by N-4 and Id-oxide is gained. (C) Elsevier, Paris.

  DOI：

  10.1016/s0223-5234(98)80013-5
• 作为产物：
  描述：

  2-硝基-5-氯苯基肼 在 盐酸 、 sodium hydroxide 、 溶剂黄146 作用下， 以 乙醇 为溶剂， 反应 12.0h， 生成 8-ethoxypyrazolo[5,1-c][1,2,4]-benzotriazine 5-oxide
  参考文献：
  名称：

  1-（2-硝基苯基）-5-氨基吡唑在碱性条件下的反应性和新的3-，7-和8-取代的吡唑并[5,1- c ] [1,2,4]苯并三嗪5-氧化物的合成，作为苯二氮杂receptor受体配体

  摘要：

  对1-（2-硝基苯基）-5-氨基吡唑在碱性条件下的反应进行了重新研究，并通过光谱法证实了所获得的吡唑并[5,1- c ] [1,2,4]苯并三嗪5-氧化物的结构。特别地，确定了对8-氯衍生物4a和6a以及7-硝基衍生物11a和12a的不同芳族亲核攻击。从这些后面的化合物意外（苯基ONN -azoxy）吡唑类中分离得到。

  DOI：

  10.1002/jhet.5570310612

文献信息

• 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。
• 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。
• Reactivity of 1-(2-nitrophenyl)-5-aminopyrazoles under basic conditions and synthesis of new 3-, 7-, and 8-substituted pyrazolo[5,1-<i>c</i>][1,2,4]benzotriazine 5-oxides, as benzodiazepine receptor ligands
  作者：Annarella Costanzo、Gabriella Guerrini、Fabrizio Bruni、Silvia Selleri

  DOI：10.1002/jhet.5570310612

  日期：1994.11

  1-(2-nitrophenyl)-5-aminopyrazoles under basic conditions has been reinvestigated and the structures of the obtained pyrazolo[5,1-c][1,2,4]benzotriazine 5-oxides confirmed by spectroscopic means. In particular the different aromatic nucleophilic attack on 8-chloro derivatives 4a and 6a and 7-nitro derivatives 11a and 12a was determined. From these latter compounds unexpected (phenyl-ONN-azoxy)pyrazoles were isolated

  对1-（2-硝基苯基）-5-氨基吡唑在碱性条件下的反应进行了重新研究，并通过光谱法证实了所获得的吡唑并[5,1- c ] [1,2,4]苯并三嗪5-氧化物的结构。特别地，确定了对8-氯衍生物4a和6a以及7-硝基衍生物11a和12a的不同芳族亲核攻击。从这些后面的化合物意外（苯基ONN -azoxy）吡唑类中分离得到。
• Benzodiazepine receptor ligands — Part II. Synthesis and biological evaluation of pyrazolo[5,1-c][1,2,4]benzotriazine 4-oxide
  作者：Annarella Costanzo、Gabriella Guerrini、Fabrizio Bruni、Giovanna Ciciani、Silvia Selleri、Silvia Cappelletti、Barbara Costa、Claudia Martini、Antonio Lucacchini

  DOI：10.1016/s0223-5234(98)80013-5

  日期：1998.3

  A new series of 3-, 8-substituted pyrazolo[5,1-c][1,2,4]benzotriazine 4-oxides 3 were synthesized and their benzodiazepine receptor (BZR) affinities were evaluated in vitro in comparison with their 5-oxide isomers 2. The 4-oxide compounds 3c,m,n,o showed a better receptor affinity than their corresponding 5-oxide isomers, with an efficacy trend of antagonist/partial inverse agonist. From a structure-affinity relationship point of view some insight in the role played by N-4 and Id-oxide is gained. (C) Elsevier, Paris.