1-oxyl-2-(2,4-dimethoxyphenyl)-3-oxo-4,4,5,5-tetramethyl-2-imidazoline | 898562-20-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 1-oxyl-2-(2,4-dimethoxyphenyl)-3-oxo-4,4,5,5-tetramethyl-2-imidazoline
• 英文别名: 2-(2',4'-dimethoxyphenyl)-4,4,5,5-tetramethylimidazolidine-3-oxide-1-oxyl；2-(2′,4′-dimethoxyphenyl)-4,4,5,5-tetramethyl-imidazolyl-1-oxyl-3-oxide
• CAS: 898562-20-4
• 化学式: C₁₅H₂₁N₂O₄
• 分子量: 293.343
• InChiKey: NSGFAQJKORCOOK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  21
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.53
• 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：

  1-oxyl-2-(2,4-dimethoxyphenyl)-3-oxo-4,4,5,5-tetramethyl-2-imidazoline 在 盐酸 、 sodium nitrite 作用下， 以 甲醇 为溶剂， 反应 1.0h， 以64%的产率得到1-oxyl-2-(2,4-dimethoxyphenyl)-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 1-oxyl-2-(2,4-dimethoxyphenyl)-3-oxo-4,4,5,5-tetramethyl-2-imidazoline
  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

• 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
• Slow magnetic relaxation and field-induced metamagnetism in nitronyl nitroxide-Dy(<scp>iii</scp>) magnetic chains
  作者：Xiufeng Wang、Yungai Li、Peng Hu、Juanjuan Wang、Licun Li

  DOI：10.1039/c4dt01878h

  日期：——

  susceptibilities show that the directly bonded nitronyl nitroxide interacts ferromagnetically with Gd and Dy ions. The Dy complex exhibits three-step metamagnetism and frequency-dependent ac magnetic susceptibilities, indicating single-chain magnet behavior. This work shows that the magnetic behaviors of one-dimensional Ln-nitronyl nitroxide chains can be fine tuned by the substituents of the radicals

  镧系离子和硝酰基氮氧化物自由基的结合产生了四个新的Ln自由基一维化合物，即[Ln（hfac）3 NIT-Ph（OMe）2 }] n（Ln III = Sm（1），Eu （2），Gd（3），Dy（4）; hfac =六氟乙酰丙酮; NIT-Ph（OMe）2 = 2-（2'，4'-二甲氧基苯基）-4,4,5,5-四甲基-4， 5-二氢-1 H-咪唑基-1-氧基-3-氧化物）。发现这四个络合物是同构的，并显示出硝酰基硝基氧自由基桥接的镧系元素线性链。直流磁化率表明，直接键合的亚硝酰氮氧化物与Gd和Dy离子发生铁磁相互作用。Dy复合物表现出三步超磁性和频率相关的交流磁化率，表明单链磁体行为。这项工作表明，一维Ln-亚硝基硝基氮氧化物链的磁性行为可以通过自由基的取代基进行微调。
• Nitronyl nitroxide based 2p–3d–4f chains with the magnetocaloric effect and slow magnetic relaxation
  作者：Xiufeng Wang、Cun Li、Juan Sun、Licun Li

  DOI：10.1039/c5dt02783g

  日期：——

  Ln(hfac)3 and Cu(hfac)2 units are bridged by nitronyl nitroxide radicals through the NO groups. DC magnetic studies found that ferromagnetic interactions between metals and the coordinated NO groups are active in all four compounds. The Tb derivative displays frequency dependent ac magnetic susceptibilities, indicating slow magnetic relaxation behavior. The Gd complex shows an important cryogenic magnetocaloric

  四种新的基于硝酰基硝基氧自由基的杂三旋一维化合物，即[Ln（hfac）3 } 3 Cu（hfac）2 } NIT-Ph（OMe）2 } 4 ] n（Ln = Gd（1），Tb（2），Dy（3），Er（4）; hfac =六氟乙酰丙酮; NIT–Ph（OMe）2 = 2-（2'，4'-二甲氧基苯基）-4,4,5,5-已经成功制备了四甲基-咪唑基-1-氧基-3-氧化物。单晶X射线晶体学分析表明，配合物1-4具有一维链结构，具有重复的[Cu–Rad–Ln–Rad–Ln–Rad–Ln–Rad]部分，其中Ln（hfac）3Cu（hfac）2单元通过亚硝酰基氮氧化物自由基通过NO基团桥接。直流磁研究发现，金属与配位的NO基团之间的铁磁相互作用在所有四种化合物中均有效。Tb导数显示出随频率变化的交流磁化率，表明缓慢的磁弛豫行为。所谓Gd复合节目与熵变（-Δ一个重要的低温磁致热效应小号米13.5Ĵ千克）-1
• 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.