[2-(1,3-苯并二氧戊环-5-基)-4,4,5,5-四甲基-3-氧代-4,5-二氢-1H-咪唑-1-基]氧氮自由基 | 228712-12-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并间二氧杂环戊烯类
• 中文名称: [2-(1,3-苯并二氧戊环-5-基)-4,4,5,5-四甲基-3-氧代-4,5-二氢-1H-咪唑-1-基]氧氮自由基
• 英文名称: 2-(3',4'-dioxylmethylene-phenyl)-4,4,5,5-tetramethyl-imidazoline-1-oxyl-3-oxide
• CAS: 228712-12-7
• 化学式: C₁₄H₁₇N₂O₄
• 分子量: 277.3
• InChiKey: HNXQRKMAQIMYLB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  20
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  51.4
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  [2-(1,3-苯并二氧戊环-5-基)-4,4,5,5-四甲基-3-氧代-4,5-二氢-1H-咪唑-1-基]氧氮自由基 在 盐酸 、 sodium nitrite 作用下， 以 甲醇 为溶剂， 反应 1.0h， 以81%的产率得到1-oxyl-2-(3,4-methylenedioxyphenyl)-4,4,5,5-tetramethyl-2-imidazoline
  参考文献：
  名称：

  Novel 1-oxyl-2-substitutedphenyl-4,4,5,5-tetramethylimidazolines: Synthesis, selectively analgesic action, and QSAR analysis

  摘要：

  Based on the knowledge that imidazoline can result in analgesic action due to its selective binding with the prostacyclin receptor, 20 1-oxyl-2-substitutedphenyl-4,4,5,5-tetramethylimidazolines (3a-t) were prepared in moderate yields. At 0.13 mmol/kg dose, their in vivo analgesic activities were evaluated after the mice were administered at 30, 60, 90, and 150 min. Compared with the pain threshold (12.27 +/- 9.56-17.71 +/- 7.00%) of normal saline (NS) receiving mice, the pain threshold (23.42 +/- 8.14% to 102.58 +/- 10.66%) of 3a-t receiving mice increases significantly. Considering a prostacyclin receptor targeting analgesic agent usually had bleeding action and to appraise the bleeding risk, the in vivo tail bleeding time of 1.30 mmol/kg 3a-t receiving mice was found to be ranged from 116.3 +/- 8.2 s to 120.3 +/- 9.2 s, which was substantially equal to that (117.8 +/- 8.4 s to 119.0 +/- 8.6 s) of NS receiving mice. Based on the possibility of imidazoline acting as vasodilator, the in vitro vasorelaxations of 3a-t were tested using the rat aortic strip model. When the aortic strip contracted by noradrenaline (NE, final concentration 10(-7) mol/l) was treated with 3a-t (final concentration 5 x 10(-4) mol/l), only lower percentage inhibitions (6.55 +/- 5.70-37.40 +/- 4.07%) were recorded, implying that the vasorelaxation of 3a-t was neglectable. By selecting appropriate molecular descriptors generated from e-dragon server, the QSAR model of the analgesic activities of 3a-t was constructed using the multiple linear regression method. The established QSAR model showed reasonable accuracy and thus it is promising to be used for screening new 1-oxyl-2-substitutedphenyl-4,4,5,5-tetramethylimidazoline derivatives as analgesic agents. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2007.02.023
• 作为产物：
  描述：

  2,3-二甲基-2,3-二硝基丁烷 在 氯化铵 、 lead dioxide 、 锌 作用下， 以 四氢呋喃 、 甲醇 、 水 为溶剂， 反应 35.33h， 生成 [2-(1,3-苯并二氧戊环-5-基)-4,4,5,5-四甲基-3-氧代-4,5-二氢-1H-咪唑-1-基]氧氮自由基
  参考文献：
  名称：

  作为自由基清除剂的新型2-取代硝酰基硝基氧化合物：合成，生物学评估和结构-活性关系。

  摘要：

  为了开发具有增强的自由基清除剂性能的更有效的小分子，我们设计并合成了一系列硝酰基硝基氧衍生物4a-h。基于Ach诱导的血管舒张测定法发现了前导化合物4f。基于该支架的进一步化学修饰提供了一系列新的2-取代的苯基亚硝酰基硝基氧化物衍生物6a-s。基于PC12细胞存活测定法，新合成的化合物6a-s具有改善的自由基清除剂的活性。就NO，H（2）O（2）和OH的清除能力而言，化合物6g，n，o和s是一些最有效的化合物。2-取代的苯基亚硝基硝基氮氧化物具有较高的自由基清除活性，带有给电子基团（EDG）。相比之下，吸电子基团（EWG）引入芳环导致其自由基清除活性急剧下降。这些结果表明，芳香环的给电子基团（EDG）可能是影响这些化合物清除自由基行为的重要因素，清除自由基的能力很大程度上取决于苯环的位置和电子性质。取代基。新型的2-取代的硝酰基氮氧化物的增强的自由基清除能力可能是对抗ROS（活性氧）/ R

  DOI：

  10.1016/j.bmc.2006.04.016

文献信息

• Four new rare-earth nitronyl nitroxide radical complexes: Magnetic and luminescent properties
  作者：Shuai-Liang Yang、Rui-Rui Wang、Xiao-Jiao Jin、Chen-Xi Zhang、Qing-Lun Wang

  DOI：10.1016/j.poly.2017.12.030

  日期：2018.4

  Abstract Four new rare-earth nitronyl nitroxide radical complexes, [Ln(hfac)3(NITPh-Pa)2][0.5CH3(CH2)5CH3] (Ln = Gd(1), Tb(2), Dy(3), Ho(4), hfac = hexafluoroacetylacetonate, NITPh-Pa = 2-(3′,4′-dioxylmethylene-phenyl)-4,4,5,5-tetramethyl-imidazoline-1-oxyl-3-oxide), have been synthesized. The X-ray crystal structure analysis revealed that four compounds have similar mononuclear tri-spin structures, in which

  摘要四种新的稀土硝酰基氮氧自由基自由基络合物[Ln（hfac）3（NITPh-Pa）2] [0.5CH3（CH2）5CH3]（Ln = Gd（1），Tb（2），Dy（3）， Ho（4），hfac =六氟乙酰丙酮，NITPh-Pa = 2-（3'，4'-二氧基亚甲基-苯基）-4,4,5,5-四甲基咪唑啉-1-氧基-3-氧化物）合成的。X射线晶体结构分析表明，四种化合物具有相似的单核三旋结构，其中Ln（III）离子由两个硝酰基硝基氧自由基和三个六氟乙酰丙酮酸酯配体八配位，形成略微扭曲的十二面体。在配合物1-4中，孤立的单核分子通过分子间氢键相互连接，形成3D超分子框架。磁性研究表明，配合物1中的Gd（III）离子与自由基之间存在铁磁相互作用。配合物2和3的交流（ac）磁化率表明不存在非零的异相信号，这表明不存在慢磁弛豫。配合物2的发光性质表现出Tb3 +离子的特征发射峰以及识别Cr2O72-和Cr3
• A novel rare-earth nitronyl nitroxide radical complex as a high-efficiency sensor for Cr³⁺ and Cr₂O₇²⁻ ions in aqueous solutions
  作者：Yue-Ying Yuan、Yu-Jun Sun、Peng-Jing Liu、Chen-Xi Zhang、Qing-Lun Wang

  DOI：10.1080/24701556.2019.1569688

  日期：2018.9.2

  a new complex with formula [Eu(hfac)3(NITPh-DOMe)2] (1) (hfac = hexafluoroacetylacetonate, NITPh-DOMe =2-(3′,4′-dioxylmethylene-phenyl)-4,4,5,5-tetramethyl-imidazoline-1-oxyl-3-oxide) has been successfully synthesized. Central Eu(III) ions of complex 1 are eight coordinated by two NITPh-DOMe radicals and three hexafluoroacetylacetonate ligands. The luminescent explorations show that complex 1 with

  在本文中，式[Eu（hfac）3（NITPh-DOMe）2 ]（1）（hfac =六氟乙酰丙酮，NITPh-DOMe = 2-（3'，4'-二氧亚甲基-苯基）-4，已经成功合成了4,5,5-四甲基-咪唑啉-1-氧基-3-氧化物。配合物1的中央Eu（III）离子由两个NITPh-DOMe自由基和三个六氟乙酰丙酮酸酯配体配位。发光探索表明络合物1具有高灵敏度，选择性，几乎是线性的低浓度和检测Cr的低检测限3+（1μM）和Cr 2 ö 7 2 -（0.1μM）在水溶液中的离子。
• Novel 2-substituted nitronyl nitroxides as free radical scavengers: Synthesis, biological evaluation and structure–activity relationship
  作者：Yihui Wu、Lanrong Bi、Wei Bi、Zeng Li、Ming Zhao、Chao Wang、Jingfang Ju、Shiqi Peng

  DOI：10.1016/j.bmc.2006.04.016

  日期：2006.8

  nitroxide derivatives 4a-h. A lead compound 4f was discovered based on Ach-induced vascorelaxation assay. Further chemical modification based on this scaffold provided a new series of 2-substituted phenylnitronyl nitroxide derivatives 6a-s. The newly synthesized compounds 6a-s possess improved radical scavenger's activity based on PC12 cell survival assay. Compounds 6g,n,o, and s are some of the most

  为了开发具有增强的自由基清除剂性能的更有效的小分子，我们设计并合成了一系列硝酰基硝基氧衍生物4a-h。基于Ach诱导的血管舒张测定法发现了前导化合物4f。基于该支架的进一步化学修饰提供了一系列新的2-取代的苯基亚硝酰基硝基氧化物衍生物6a-s。基于PC12细胞存活测定法，新合成的化合物6a-s具有改善的自由基清除剂的活性。就NO，H（2）O（2）和OH的清除能力而言，化合物6g，n，o和s是一些最有效的化合物。2-取代的苯基亚硝基硝基氮氧化物具有较高的自由基清除活性，带有给电子基团（EDG）。相比之下，吸电子基团（EWG）引入芳环导致其自由基清除活性急剧下降。这些结果表明，芳香环的给电子基团（EDG）可能是影响这些化合物清除自由基行为的重要因素，清除自由基的能力很大程度上取决于苯环的位置和电子性质。取代基。新型的2-取代的硝酰基氮氧化物的增强的自由基清除能力可能是对抗ROS（活性氧）/ R
• Novel 1-oxyl-2-substitutedphenyl-4,4,5,5-tetramethylimidazolines: Synthesis, selectively analgesic action, and QSAR analysis
  作者：Ming Zhao、Zheng Li、Li Peng、Yu-Rong Tang、Chao Wang、Ziding Zhang、Shiqi Peng

  DOI：10.1016/j.bmc.2007.02.023

  日期：2007.4

  Based on the knowledge that imidazoline can result in analgesic action due to its selective binding with the prostacyclin receptor, 20 1-oxyl-2-substitutedphenyl-4,4,5,5-tetramethylimidazolines (3a-t) were prepared in moderate yields. At 0.13 mmol/kg dose, their in vivo analgesic activities were evaluated after the mice were administered at 30, 60, 90, and 150 min. Compared with the pain threshold (12.27 +/- 9.56-17.71 +/- 7.00%) of normal saline (NS) receiving mice, the pain threshold (23.42 +/- 8.14% to 102.58 +/- 10.66%) of 3a-t receiving mice increases significantly. Considering a prostacyclin receptor targeting analgesic agent usually had bleeding action and to appraise the bleeding risk, the in vivo tail bleeding time of 1.30 mmol/kg 3a-t receiving mice was found to be ranged from 116.3 +/- 8.2 s to 120.3 +/- 9.2 s, which was substantially equal to that (117.8 +/- 8.4 s to 119.0 +/- 8.6 s) of NS receiving mice. Based on the possibility of imidazoline acting as vasodilator, the in vitro vasorelaxations of 3a-t were tested using the rat aortic strip model. When the aortic strip contracted by noradrenaline (NE, final concentration 10(-7) mol/l) was treated with 3a-t (final concentration 5 x 10(-4) mol/l), only lower percentage inhibitions (6.55 +/- 5.70-37.40 +/- 4.07%) were recorded, implying that the vasorelaxation of 3a-t was neglectable. By selecting appropriate molecular descriptors generated from e-dragon server, the QSAR model of the analgesic activities of 3a-t was constructed using the multiple linear regression method. The established QSAR model showed reasonable accuracy and thus it is promising to be used for screening new 1-oxyl-2-substitutedphenyl-4,4,5,5-tetramethylimidazoline derivatives as analgesic agents. (c) 2007 Elsevier Ltd. All rights reserved.