8-iodopyrazolo[5,1-c][1,2,4]benzotriazine 5-oxide | 933473-11-1

• 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-iodopyrazolo[5,1-c][1,2,4]benzotriazine 5-oxide
• 英文别名: 8-Iodo-5-oxidopyrazolo[5,1-c][1,2,4]benzotriazin-5-ium
• CAS: 933473-11-1
• 化学式: C₉H₅IN₄O
• 分子量: 312.069
• InChiKey: LLLZYDAQBWVIAS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  15
• 可旋转键数：
  0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 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：

  8-iodopyrazolo[5,1-c][1,2,4]benzotriazine 5-oxide 在 溴 作用下， 以 氯仿 为溶剂， 以90%的产率得到3-Bromo-8-iodo-5-oxidopyrazolo[5,1-c][1,2,4]benzotriazin-5-ium
  参考文献：
  名称：

  新型3-碘-8-乙氧基吡唑并[5,1-c] [1,2,4]苯并三嗪5-氧化物作为有前途的先导，可用于设计α5反向激动剂，用于治疗记忆损伤。

  摘要：

  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。

  DOI：

  10.1016/j.bmc.2007.01.053
• 作为产物：
  描述：

  ethyl 1-(2-nitro-5-iodophenyl)-5-aminopyrazole-4-carboxylate 在 盐酸 、 sodium hydroxide 作用下， 以 水 为溶剂， 反应 11.0h， 生成 8-iodopyrazolo[5,1-c][1,2,4]benzotriazine 5-oxide
  参考文献：
  名称：

  新型3-碘-8-乙氧基吡唑并[5,1-c] [1,2,4]苯并三嗪5-氧化物作为有前途的先导，可用于设计α5反向激动剂，用于治疗记忆损伤。

  摘要：

  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。

  DOI：

  10.1016/j.bmc.2007.01.053

文献信息

• Synthesis of new pyrazolo[5,1-c][1,2,4] benzotriazines, pyrazolo[5,1-c]pyrido[4,3-e][1,2,4] triazines and their open analogues as cytotoxic agents in normoxic and hypoxic conditions
  作者：Giovanna Ciciani、Marcella Coronnello、Gabriella Guerrini、Silvia Selleri、Miriam Cantore、Paola Failli、Enrico Mini、Annarella Costanzo

  DOI：10.1016/j.bmc.2008.09.055

  日期：2008.11

  The synthesis and antitumor activity in normoxic and hypoxic conditions of a series of pyrazolo[5,1-c][1,2,4]benzotriazine and its related analogues are reported. All compounds were tested on human colorectal adenocarcinoma cell line HCT-8 and for compounds 15 and 20, which show to have selective cytotoxicity in hypoxic and in normoxic conditions respectively, ROS production, cell cycle, and DNA fragmentation

  报道了一系列吡唑并[5,1-c] [1,2,4]苯并三嗪及其相关类似物在常氧和低氧条件下的合成和抗肿瘤活性。所有化合物均在人大肠腺癌细胞系HCT-8和化合物15和20上进行了测试，化合物15和20在低氧和常氧条件下分别显示出选择性的细胞毒性，测定了ROS的产生，细胞周期和DNA片段化。这项初步研究鼓励我们将15和20视为进一步优化的有趣线索。
• New 3-, 8-disubstituted pyrazolo[5,1-c][1,2,4]benzotriazines useful for studying the interaction with the HBp-3 area (hydrogen bond point area) in the benzodiazepine site on the γ-aminobutyric acid type A (GABAA) receptor
  作者：Gabriella Guerrini、Giovanna Ciciani、Fabrizio Bruni、Silvia Selleri、Fabrizio Melani、Simona Daniele、Claudia Martini、Annarella Costanzo

  DOI：10.1016/j.bmc.2011.04.009

  日期：2011.5

  The pharmacophoric model using ADLR procedure, based on pyrazolo[5,1-c][1,2,4]benzotriazine system, studied in our laboratory, allowed us to identify the essential interaction points (HBp-1, HBp-2, and Lp-1) and the important areas for affinity modulation (HBp-3 and Lp-2) for binding recognition at benzodiazepine (Bzs) site of GABA(A) receptors (GABA(A)-Rs). In this work ADLR method is used to rationalize the affinity data of 23 new compounds and to improve the knowledge on HBp-3 area, hydrogen bond area. Among these new compounds emerge the pyrrolo derivatives (18, 25, 28, 34, and 37) for their good affinity value (14.9 > K-i(nM) > 63.0). In the orientations proposed by ADLR, the NH moiety of the pyrrole ring, independently of the position in the pyrazolobenzotriazine core, fits in HBp-3 area and points out the acceptor feature of this hydrogen bond area, already known as donor area. Unexpectedly, the oxygen atom of the furane ring does not form efficient hydrogen bond with the same area, probably for an imperfect distance. The size of substituent at position 8 is important but not necessary for the receptor recognition, in fact the interdependence between the features of the 3- and 8-substituent's is again verified, (i.e., compound 20 vs 32). (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.