2-[1-(2-[1,3]dioxolan-2-ylphenoxy)ethyl]-4,5-dihydro-1H-imidazole | 1043534-13-9

• 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-[1,3]dioxolan-2-ylphenoxy)ethyl]-4,5-dihydro-1H-imidazole
• CAS: 1043534-13-9
• 化学式: C₁₄H₁₈N₂O₃
• 分子量: 262.309
• InChiKey: QKBUGMPLWNSPRU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  19.0
• 可旋转键数：
  4.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  52.08
• 氢给体数：
  1.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  2-[1-(2-[1,3]dioxolan-2-ylphenoxy)ethyl]-4,5-dihydro-1H-imidazole 在 盐酸 、 水 、 sodium hydroxide 作用下， 以 水 为溶剂， 反应 2.0h， 以84%的产率得到2-(1-(4,5-dihydro-1H-imidazol-2-yl)ethoxy)benzaldehyde
  参考文献：
  名称：

  Might the observed α2A-adrenoreceptor agonism or antagonism of allyphenyline analogues be ascribed to different molecular conformations?

  摘要：

  We recently reported that the alpha(2)-adrenoreceptor (AR) ligand allyphenyline (9) significantly enhanced morphine analgesia (due to its alpha(2C)-AR agonism), was devoid of sedative side effects (due to its alpha(2A)-AR antagonism), prevented and reversed morphine tolerance and dependence. To highlight the molecular characteristics compatible with this behaviour and to obtain novel agents potentially useful in chronic pain and opioid addiction management, the allyl group of 9 was replaced by substituents of moderate steric bulk (MR) and positive or negative lipophilic (pi) and electronic (sigma) contributions in all the possible combinations. Effective novel alpha(2C)-agonists/alpha(2A)-antagonists (2, 3, 10, 12, and 17) were obtained. This study also demonstrated that contradictory combinations of the physicochemical parameters were similarly able to induce the alpha(2A)-activation. Since we had previously observed that the absolute configuration affected only the potency, but not the functional profile of the ligands, we hypothesized that the alpha(2A)-activation was governed by a ligand preferred conformation. From a structural overlay investigation it emerged that an extended conformation appeared to be associated with dual alpha(2C)-agonism/alpha(2A)-antagonism, whereas a folded conformation associated with alpha(2C)-/alpha(2A)-agonism. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2012.01.035
• 作为产物：
  描述：

  2-(2-[1,3]dioxolan-2-ylphenoxy)propionitrile 、 乙二胺 在 sodium methylate 、 盐酸 作用下， 以 甲醇 为溶剂， 反应 36.0h， 以42%的产率得到2-[1-(2-[1,3]dioxolan-2-ylphenoxy)ethyl]-4,5-dihydro-1H-imidazole
  参考文献：
  名称：

  α₂-Adrenoreceptors Profile Modulation. 4. From Antagonist to Agonist Behavior

  摘要：

  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.

  DOI：

  10.1021/jm800250z