2-(1-(2-allylphenoxy)ethyl)-4,5-dihydro-1H-imidazole | 1043533-91-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 2-(1-(2-allylphenoxy)ethyl)-4,5-dihydro-1H-imidazole
• 英文别名: allyphenyline；2-[1-(2-prop-2-enylphenoxy)ethyl]-4,5-dihydro-1H-imidazole
• CAS: 1043533-91-0
• 化学式: C₁₄H₁₈N₂O
• 分子量: 230.31
• InChiKey: MNMDMCKHXVHLAW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  17
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  33.6
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  2-(2-allylphenoxy)propanenitrile 、 乙二胺 在 sodium methylate 作用下， 生成 2-(1-(2-allylphenoxy)ethyl)-4,5-dihydro-1H-imidazole
  参考文献：
  名称：

  Investigation of allyphenyline efficacy in the treatment of alcohol withdrawal symptoms

  摘要：

  We have recently demonstrated that allyphenylinc, behaving as alpha(2c)-acIrenocepLor/seroLonin 5-HT1A receptor agonist and alpha(2A)-adrenoceptor antagonist, in mice enhanced morphine analgesia, attenuated morphine withdrawal symptoms, showed significant antidepressant-like activity and was devoid of sedative side effects. Opioid and alcohol withdrawal shares several Common neurobiological and molecular mechanisms. Therefore, in this study we expanded our analysis of the pharmacological properties of allyphenyline by investigating its ability to prevent the expression of somatic withdrawal signs, anxiety-like behavior and hyperlocomotion associated with chronic ethanol intoxication. Rats were subjected to induction of ethanol dependence via repeated daily intragastric ethanol (20%) administration for 4 consecutive days. Twelve hours after the last alcohol administration, somatic alcohol withdrawal signs were scored. Results revealed a significant expression of physical withdrawal signs that were not affected by intraperitoneal (i.p.) administration of allyphenyline at the doses of 0.05, 0.275 and 0.5 mg/kg. In contrast, allyphenyline (0.05 and 0.275 mg/kg i.p.) significantly reduced hyperanxiety-like behavior observed 6 clays after alcohol intoxication as measured using the defensive burying test. Allyphenyline also reduced open field hyperlocomotor activity associated with alcohol withdrawal. Notably, the anxiolytic effect of the compound, as well as the already reported antidepressant action, was observed at very low closes, suggesting the involvement of its alpha(2c)-adrenoceptor/serotonin 5-HT1A receptor agonism. Therefore, the present investigation suggests that allyphenyline might represent an interesting pharmacological tool to investigate the potential of compounds exhibiting alpha(2c)-adrenoceptor/serotonin 5-HT1A receptor agonism and alpha(2A)-adrenoceptor antagonism in the treatment of hyperanxiety and hyperlocomotion occurring during alcohol withdrawal in dependent subjects. (C) 2015 Elsevier B.V. All rights reserved.

  DOI：

  10.1016/j.ejphar.2015.04.005

文献信息

• α₂-Adrenoreceptors Profile Modulation. 4. From Antagonist to Agonist Behavior
  作者：Francesco Gentili、Claudia Cardinaletti、Cristian Vesprini、Antonio Carrieri、Francesca Ghelfi、Aniket Farande、Mario Giannella、Alessandro Piergentili、Wilma Quaglia、Jonne M. Laurila、Anna Huhtinen、Mika Scheinin、Maria Pigini

  DOI：10.1021/jm800250z

  日期：2008.7.1

  The goal of the present study was to modulate the receptor interaction properties of known alpha(2)-adrenoreceptor (AR) antagonists to obtain novel alpha(2)-AR agonists with desirable subtype selectivity. Therefore, a phenyl group or one of its bioisosteres or aliphatic moieties with similar steric hindrance were introduced into the aromatic ring of the antagonist lead basic structure. The functional properties of the novel compounds allowed our previous observations to be confirmed. The high efficacy of 7, 12, and 13 as alpha(2)-AR agonists and the significant alpha(2C)-AR subtype selective activation displayed by 11 and 15 demonstrated that favorable interactions to induce alpha(2)-AR activation were formed between the pendant groups of the ligands and the aromatic cluster present in transmembrane domain 6 of the binding site cavity of the receptors.
• Biological profile and bioavailability of imidazoline compounds on morphine tolerance modulation
  作者：Giovanni Caprioli、Valerio Mammoli、Massimo Ricciutelli、Gianni Sagratini、Massimo Ubaldi、Esi Domi、Laura Mennuni、Chiara Sabatini、Chiara Galimberti、Flora Ferrari、Chiara Milia、Eleonora Comi、Marco Lanza、Mario Giannella、Maria Pigini、Fabio Del Bello

  DOI：10.1016/j.ejphar.2015.11.021

  日期：2015.12

  Tolerance to opioid administration represents a serious medical alert in different chronic conditions. This study compares the effects of the imidazoline compounds 1,2, and 3 on morphine tolerance in an animal model of inflammatory pain in the rat. 1,2, and 3 have been selected in that, although bearing a common scaffold, preferentially bind to alpha(2)-adrenoceptors, imidazoline 12 receptors, or both systems, respectively. Such compounds have been tested in vivo by measuring the paw withdrawal threshold to mechanical pressure after complete Freund's adjuvant injection. To determine the ligand levels in rat plasma, an HPLC-mass spectrometry method has been developed. All the compounds significantly reduced the induction of morphine tolerance, showing different potency and duration of action. Indeed, the selective imidazoline I-2 receptor interaction (2) restored the analgesic response by maintaining the same timedependent profile observed after a single morphine administration. Differently, the selective alpha(2c)-adrenoceptor activation (1) or the combination between alpha(2c)-adrenoceptor activation and imidazoline I-2 receptor engagement (3) promoted a change in the temporal profile of morphine analgesia by maintaining a mild but long lasting analgesic effect. Interestingly, the kinetics of compounds in rat plasma supported the pharmacodynamic data. Therefore, this study highlights that both peculiar biological profile and bioavailability of such ligands complement each other to modulate the reduction of morphine tolerance. Based on these observations, 1-3 can be considered useful leads in the design of new drugs able to turn off the undesired tolerance induced by opioids. (C) 2015 Elsevier B.V. All rights reserved.