3-iodo-8-chloropyrazolo[5,1-c][1,2,4]benzotriazine 5-oxide | 473272-67-2

• 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: 3-iodo-8-chloropyrazolo[5,1-c][1,2,4]benzotriazine 5-oxide
• 英文别名: 8-Chloro-3-iodo-5-oxidopyrazolo[5,1-c][1,2,4]benzotriazin-5-ium；8-chloro-3-iodo-5-oxidopyrazolo[5,1-c][1,2,4]benzotriazin-5-ium
• CAS: 473272-67-2
• 化学式: C₉H₄ClIN₄O
• 分子量: 346.514
• InChiKey: JQGBOYBINJCVKR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  16
• 可旋转键数：
  0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 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：

  3-iodo-8-chloropyrazolo[5,1-c][1,2,4]benzotriazine 5-oxide 在 四(三苯基膦)钯 sodium carbonate 、 亚磷酸三乙酯 作用下， 以 乙醇 、 甲苯 为溶剂， 反应 12.0h， 生成 3-(3-furyl)-8-chloropyrazolo[5,1-c][1,2,4]benzotriazine
  参考文献：
  名称：

  Costanzo, Annarella; Guerrini, Gabriella; Ciciani, Giovanna, Medicinal Chemistry Research, 2002, vol. 11, # 2, p. 87 - 101

  摘要：

  DOI：
• 作为产物：
  描述：

  8-chloropyrazolo[5,1-c][1,2,4]benzotriazine 5-oxide 在 一氯化碘 作用下， 以 氯仿 为溶剂， 以56%的产率得到3-iodo-8-chloropyrazolo[5,1-c][1,2,4]benzotriazine 5-oxide
  参考文献：
  名称：

  Costanzo, Annarella; Guerrini, Gabriella; Ciciani, Giovanna, Medicinal Chemistry Research, 2002, vol. 11, # 2, p. 87 - 101

  摘要：

  DOI：

文献信息

• Synthesis of novel cognition enhancers with pyrazolo[5,1- c ][1,2,4]benzotriazine core acting at γ-aminobutyric acid type A (GABA A ) receptor
  作者：Gabriella Guerrini、Giovanna Ciciani、Annarella Costanzo、Simona Daniele、Claudia Martini、Carla Ghelardini、Lorenzo Di Cesare Mannelli、Samuele Ciattini

  DOI：10.1016/j.bmc.2013.02.027

  日期：2013.4

  with a pyrazolo[5,1-c][1,2,4]benzotriazine core to identify ligands on GABAA receptors subtype (benzodiazepine site on GABAA-receptor) endowed with the potential of enhancing cognition activity without the side effects usually associated with non-selective GABAA modulators. In fact, there is much evidence that GABAA-R (γ-aminobutyric acid, type A receptor) subtype ligands have relevance in learning

  与衰老，神经退行性疾病和精神疾病相关的记忆功能障碍代表了日益增长的医疗需求。探索学习和记忆基础的生物学机制的研究进展为开发针对选择性神经元靶标的记忆增强疗法开辟了新的潜在方法。在这项工作中，我们合成了一些具有吡唑并[5,1- c ] [1,2,4]苯并三嗪核心的衍生物，以鉴定具有增强潜力的GABA A受体亚型（GABA A受体上的苯二氮卓部位）上的配体无副作用的认知活动通常与非选择性GABA A调节剂有关。实际上，有很多证据表明GABA A-R（γ-氨基丁酸，A型受体）亚型配体与学习和记忆有关。已经进行了体外和体内测试。药理学数据表明，化合物7，13，14和22充当GABA的双重功能调节剂阿-Rs（promnemonic和抗焦虑药），而仅化合物3和10立场选择性地显示良好antiamnesic和促认知活性（1和3mg /公斤）。
• Development of ligands at γ-aminobutyrric acid type A (GABAA) receptor subtype as new agents for pain relief
  作者：Gabriella Guerrini、Giovanna Ciciani、Fabrizio Bruni、Silvia Selleri、Claudia Martini、Simona Daniele、Carla Ghelardini、Lorenzo Di Cesare Mannelli、Annarella Costanzo

  DOI：10.1016/j.bmc.2011.10.047

  日期：2011.12

  The identification of compounds with selective anxiolytic-like effects, exerted through the benzodiazepine site on gamma-aminobutyric acid type A (GABA(A)) receptors, and that show pronounced antihyperalgesia in several pain models, has oriented research towards the development of new agents for the relief of pain. Starting from our previously reported ligands at the benzodiazepine site on GABA(A) receptors showing selective anxiolytic-like effects, we have designed new compounds with the aim of identifying those devoid of the typical side effects of the classical benzodiazepines. Our preliminary results indicate that compounds 4, 10(+/-) and 11 have a very promising antihyperalgesic profile in different animal pain models (peripheral mono-neuropathy, STZ-induced hyperalgesia). In particular 11 exhibits high potency since it exerted its protective effect starting from the dose of 3 mg/kg po, after single injection. (C) 2011 Elsevier Ltd. All rights reserved.
• Synthesis, in Vivo Evaluation, and Molecular Modeling Studies of New Pyrazolo[5,1-<i>c</i>][1,2,4]benzotriazine 5-Oxide Derivatives. Identification of a Bifunctional Hydrogen Bond Area Related to the Inverse Agonism
  作者：Gabriella Guerrini、Giovanna Ciciani、Giovanni Cambi、Fabrizio Bruni、Silvia Selleri、Chiara Guarino、Fabrizio Melani、Marina Montali、Claudia Martini、Carla Ghelardini、Monica Norcini、Annarella Costanzo

  DOI：10.1021/jm801599a

  日期：2009.8.13

  A new series of pyrazolo[5,1-c-][1,2,4]benzotriazine 5-oxide 8-alkyloxy-/aryloxy-/arylalkyloxy and 8-aryl-/arylalkylderivatives variously substituted at the 3-position were synthesized and binding studies at the benzodiazepine site on GABA(A) receptor were carried out. The pharmacological profile was identified for compounds 10, 11, 16(+), 16(-), and 17 by considering six potential benzodiazepine actions: motor coordination, anticonvulsant action, spontaneous motility and explorative activity, potential anxiolytic-like effects, mouse learning and memory modulation., and finally, ethanol-potentiating action. Compound 17 stands out as the compound that improves mouse memory processes selectively, safely, and in a statistically significant manner. From a ligand-based pharmacophoric model, we identified a hydrogen bond interaction area HBp-3 near the lipophilic area. This new pharmacophoric model allowed us to identify four structural compound typologics and thus to rationalize the affinity data of all compounds.