1,3-dihydroxy-2-(2'-hydroxyphenyl)-4,4,5,5-tetramethylimidazolidine | 626206-01-7

• 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-(2'-hydroxyphenyl)-4,4,5,5-tetramethylimidazolidine
• 英文别名: 2-(2-Hydroxyphenyl)-4,4,5,5-tetramethylimidazolidine-1,3-diol；2-(1,3-dihydroxy-4,4,5,5-tetramethylimidazolidin-2-yl)phenol
• CAS: 626206-01-7
• 化学式: C₁₃H₂₀N₂O₃
• 分子量: 252.313
• InChiKey: ZFYQBMRUUBDBLE-UHFFFAOYSA-N

物化性质

• 熔点：
  154-155 °C(Solv: chloroform (67-66-3))
• 沸点：
  367.8±42.0 °C(Predicted)
• 密度：
  1.235±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  18
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  67.2
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  1,3-dihydroxy-2-(2'-hydroxyphenyl)-4,4,5,5-tetramethylimidazolidine 在 magnesium sulfate 作用下， 以 四氢呋喃 为溶剂， 反应 24.0h， 以115 mg的产率得到2-[(3-hydroxy-4,4,5,5-tetramethylimidazoline)-2-yl]phenol
  参考文献：
  名称：

  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

  摘要：

  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.

  DOI：

  10.1016/j.ejmech.2007.07.007
• 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-(2'-hydroxyphenyl)-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

• Design, synthesis and biological evaluation of novel nitric oxide donors with antioxidative activity
  作者：Jing Liang、Pengfei Zhang、Hongyan Yang、Ying Zhang、Tuanli Yao、Keke Liu、Yukun Wang、Xing Zhang、Xiangyang Qin

  DOI：10.1016/j.ejmech.2022.114331

  日期：2022.6

  of novel epimeric nitroxide-nitrate conjugates (15(S) and 15(R)), which had pharmacophore connections. We also synthesized 8 NIT radicals without 5-ISMN in order to compare the activities of these novel nitric oxide donors. Several dual-acting nitroxide-based nitrate conjugates showed the ability to release NO and cause anti-oxidant effects in human umbilical vein endothelial cells. Among these conjugates

  活性氧（ROS）是有机硝酸盐药物耐受和内皮功能障碍的主要原因。为了清除 ROS 并维持硝酸盐的治疗效果，我们将 NIT 型氮氧化物和 5-ISMN 结合，设计并合成了 10 种新型双作用硝酸盐分子。其中包括两种新型差向异构氮氧化物-硝酸盐偶联物（15( S )和15( R ))，它具有药效团连接。我们还合成了 8 个不含 5-ISMN 的 NIT 自由基，以比较这些新型一氧化氮供体的活性。几种基于双效氮氧化物的硝酸盐缀合物显示出在人脐静脉内皮细胞中释放 NO 并引起抗氧化作用的能力。在这些缀合物中，15( S )表现出最显着的促血管舒张作用。在血管紧张素 II 输注诱导的高血压小鼠中，15( S )治疗 4 周降低了收缩压和舒张压，并改善了孤立胸主动脉的血管内皮和平滑肌功能。此外，小鼠血管结构得到恢复，血管氧化应激降低。结果表明，这些新型一氧化氮供体可用作治疗血管疾病的潜在药物。因此，结合使用抗氧化剂和
• 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.