1,3-dihydroxy-2-(3',4'-dimethoxyphenyl)-4,4,5,5-tetramethylimidazolidine | 898562-13-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑烷类
• 英文名称: 1,3-dihydroxy-2-(3',4'-dimethoxyphenyl)-4,4,5,5-tetramethylimidazolidine
• 英文别名: 2-(3,4-Dimethoxyphenyl)-1,3-dihydroxy-4,4,5,5-tetramethylimidazolidine
• CAS: 898562-13-5
• 化学式: C₁₅H₂₄N₂O₄
• 分子量: 296.367
• InChiKey: JTCMIPXIHOUFJP-UHFFFAOYSA-N

物化性质

• 熔点：
  147-149 °C
• 沸点：
  429.7±45.0 °C(Predicted)
• 密度：
  1.167±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  21
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  65.4
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  1,3-dihydroxy-2-(3',4'-dimethoxyphenyl)-4,4,5,5-tetramethylimidazolidine 在 四丙基高钌酸铵 、 N-甲基吗啉氧化物 作用下， 以 二氯甲烷 为溶剂， 反应 1.5h， 以90%的产率得到1-oxyl-2-(3,4-dimethoxyphenyl)-3-oxo-4,4,5,5-tetramethyl-2-imidazoline
  参考文献：
  名称：

  TPAP/NMO System as a Novel Method for the Synthesis of Nitronyl Nitroxide Radicals

  摘要：

  利用四-N-丙基铵过钌酸盐/N-甲基吗啉 N-氧化物（TPAP/NMO）体系，可以轻松地将二羟基咪唑烷衍生物氧化成硝基亚硝基自由基（NNRs）。该方法在操作简单、产量高、成本低和 "绿色 "化学方面具有诸多优势。

  DOI：

  10.1055/s-2006-939045
• 作为产物：
  描述：

  2,3-二甲基-2,3-二硝基丁烷 在 氯化铵 、 锌 作用下， 以 四氢呋喃 、 甲醇 、 水 为溶剂， 反应 35.0h， 生成 1,3-dihydroxy-2-(3',4'-dimethoxyphenyl)-4,4,5,5-tetramethylimidazolidine
  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
• TPAP/NMO System as a Novel Method for the Synthesis of Nitronyl Nitroxide Radicals
  作者：Lapo Gorini、Andrea Caneschi、Stefano Menichetti

  DOI：10.1055/s-2006-939045

  日期：——

  An easy oxidation of dihydroxyimidazolidine derivatives to nitronyl nitroxide radicals (NNRs) can be achieved using the tetra-N-propylamonium perruthenate/N-methylmorpholine N-oxide (TPAP/NMO) system. The procedure offers several advantages in terms of simplicity, yield, cost and ‘green’ chemistry.

  利用四-N-丙基铵过钌酸盐/N-甲基吗啉 N-氧化物（TPAP/NMO）体系，可以轻松地将二羟基咪唑烷衍生物氧化成硝基亚硝基自由基（NNRs）。该方法在操作简单、产量高、成本低和 "绿色 "化学方面具有诸多优势。
• A new class of analgesic agents toward prostacyclin receptor inhibition: Synthesis, biological studies and QSAR analysis of 1-hydroxyl-2-substituted phenyl-4,4,5,5-tetramethylimidazolines
  作者：Ming Zhao、Zheng Li、Li Peng、Yu-Rong Tang、Chao Wang、Ziding Zhang、Shiqi Peng

  DOI：10.1016/j.ejmech.2007.07.007

  日期：2008.5

  By studying the structural similarity of analgesic imidazolines and 2-phenylnitronyl nitroxides, 20 1-hydroxyl-2-substituted phenyl-4,4,5,5-tetramethylimidazolines (2a-t) were newly synthesized as selective antagonists of prostacyclin receptor (IP receptor). In the in vivo tail-flick assay, 2a-t (dose, 0.13 mmol/kg) receiving mice showed increased pain thresholds ranging from 20.52 +/- 7.25% to 90.94 +/- 11.97%, which were significantly higher than that ranged from 12.27 +/- 9.56% to 17.71 +/- 7.00% shown by normal saline (NS) receiving mice. In the in vivo tail bleeding assay, 2a-t (dose, 1.30 mmol/kg) receiving mice gave a bleeding time ranging from 116.3 +/- 8.0 s to 119.6 +/- 7.1 s, and NS receiving mice gave a bleeding time ranging from 116.7 +/- 7.5 s to 119.1 +/- 8.7 s, which were at a substantially equal level. These observations imply that no bleeding risk occurred even when 10-fold dose of analgesic assay was used. In the in vitro vasorelaxation assay, it was found that when the aortic strip contracted by noradrenaline (NE, final concentration, 10(-7) M) was treated with the solution of 2a-t in NS (final concentration, 5 x 10(-3) M) only lower percentage inhibitions ranged from 6.63 +/- 2.72% to 46.28 +/- 2.63% were recorded. Relatively higher concentration of 2a-t (5 x 10(-3) M) and relatively lower percentage inhibitions (13 of 20 less than 23.27 +/- 3.47%) suggest that 2a-t exhibit few vasodilation activity. To shed some light on the potential analgesic mechanisms of 2a-t, moreover, a QSAR analysis was carried out by using the multiple linear regression method. Taken altogether, the current study confirms that as selective antagonist of IP receptor 1-hydroxyl-2-substituted phenyl-4,4,5,5-tetramethylimidazoline may be a promising lead compound of analgesic agent without cardiovascular and bleeding side effects. (C) 2007 Elsevier Masson SAS. All rights reserved.
• 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.