Ethyl 2-(4-tert-butyl-2,6-dimethylphenyl)ethanimidate | 208719-08-8

• 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: Ethyl 2-(4-tert-butyl-2,6-dimethylphenyl)ethanimidate
• CAS: 208719-08-8
• 化学式: C₁₆H₂₅NO
• 分子量: 247.381
• InChiKey: ZIWJBERLYLPXRB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  18
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  33.1
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  Ethyl 2-(4-tert-butyl-2,6-dimethylphenyl)ethanimidate 在 palladium on activated charcoal 作用下， 以 乙醇 、 甲苯 为溶剂， 反应 4.0h， 生成 2-[(4-t-butyl-2,6-dimethylphenyl)methyl]-1-methylimidazole
  参考文献：
  名称：

  Imidazoline-modified benzylimidazolines as h5-HT1D/1B serotonergic ligands

  摘要：

  Sumatriptan, a h5-HT1D and h5-HT1B receptor agonist used clinically as a migraine-abortive, produces certain side effects thought to result from its affinity for h(5)-HT1B receptors. The present investigation extends our work with benzylimidazolines as novel non-tryptamine h5-(HT1D/1B) ligands. The effect of N-methylation, N-benzylation, ring-aromatization, and variation of the imidazoline ring on affinity both at h5-HT1D and h5-HT1B receptors was examined. Several compounds were identified with good affinity and enhanced(i.e., > 100-fold) h5-HT1D versus h5-HT1B selectivity. (C) 2001 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(00)00275-3
• 作为产物：
  描述：

  乙醇 、 (4-叔丁基-2,6-二甲基苯基)乙腈 在 盐酸 作用下， 以 乙醚 、 乙醇 为溶剂， 反应 2.0h， 以56%的产率得到Ethyl 2-(4-tert-butyl-2,6-dimethylphenyl)ethanimidate
  参考文献：
  名称：

  Benzylimidazolines as h5-HT_1B/1D Serotonin Receptor Ligands: A Structure−Affinity Investigation

  摘要：

  Benzylimidazolines may represent a class of 5-HT1D ligands that has yet to be exploited. On the basis of a previous report that the 2-(substituted-benzyl)imidazoline alpha-adrenergic agonist oxymetazoline (8) binds with high affinity at calf brain 5-HT1D receptors, we explored the structure-affinity relationships of a series of related derivatives. Each of the aromatic substituents was removed and then reinstated in a systematic manner to determine the influence of the individual substituents on binding. It was found that all of the aromatic substituents of 8 act in concert to impart high affinity. However, although the 3-hydroxy group could be removed without significantly reducing affinity for h5-HT1D (i.e., human 5-HT1D alpha) receptors, this modification reduced h5-HT1B (i.e., human 5-HT1D beta) receptor affinity by nearly 50-fold. The 2,6-dimethyl groups also contribute to binding but seem to play a greater role for h5-HT1B binding than h5-HT1D binding.With the appropriate structural modifications, several compounds were identified that display 20- to >100-fold selectivity for h5-HT1D versus h5-HT1B receptors. Preliminary functional data suggest that these compounds behave as agonists. Given that 5-HT1D agonists are currently being explored for their antimigraine action and that activation of h5-HT1B receptors might be associated with cardiovascular side effects, h5-HT1D-selective agents may offer a new lead for the development of therapeutically efficacious agents.

  DOI：

  10.1021/jm970513p

文献信息

• Imidazoline-modified benzylimidazolines as h5-HT1D/1B serotonergic ligands
  作者：Thomas Prisinzano、Ho Law、Małgorzata Dukat、Abdelmalik Slassi、Neil MaClean、Lidia Demchyshyn、Richard A. Glennon

  DOI：10.1016/s0968-0896(00)00275-3

  日期：2001.3

  Sumatriptan, a h5-HT1D and h5-HT1B receptor agonist used clinically as a migraine-abortive, produces certain side effects thought to result from its affinity for h(5)-HT1B receptors. The present investigation extends our work with benzylimidazolines as novel non-tryptamine h5-(HT1D/1B) ligands. The effect of N-methylation, N-benzylation, ring-aromatization, and variation of the imidazoline ring on affinity both at h5-HT1D and h5-HT1B receptors was examined. Several compounds were identified with good affinity and enhanced(i.e., > 100-fold) h5-HT1D versus h5-HT1B selectivity. (C) 2001 Elsevier Science Ltd. All rights reserved.
• Benzylimidazolines as h5-HT_1B/1D Serotonin Receptor Ligands: A Structure−Affinity Investigation
  作者：Ho Law、Malgorzata Dukat、Milt Teitler、David K. H. Lee、Lucia Mazzocco、Raj Kamboj、Vik Rampersad、Thomas Prisinzano、Richard A. Glennon

  DOI：10.1021/jm970513p

  日期：1998.6.1

  Benzylimidazolines may represent a class of 5-HT1D ligands that has yet to be exploited. On the basis of a previous report that the 2-(substituted-benzyl)imidazoline alpha-adrenergic agonist oxymetazoline (8) binds with high affinity at calf brain 5-HT1D receptors, we explored the structure-affinity relationships of a series of related derivatives. Each of the aromatic substituents was removed and then reinstated in a systematic manner to determine the influence of the individual substituents on binding. It was found that all of the aromatic substituents of 8 act in concert to impart high affinity. However, although the 3-hydroxy group could be removed without significantly reducing affinity for h5-HT1D (i.e., human 5-HT1D alpha) receptors, this modification reduced h5-HT1B (i.e., human 5-HT1D beta) receptor affinity by nearly 50-fold. The 2,6-dimethyl groups also contribute to binding but seem to play a greater role for h5-HT1B binding than h5-HT1D binding.With the appropriate structural modifications, several compounds were identified that display 20- to >100-fold selectivity for h5-HT1D versus h5-HT1B receptors. Preliminary functional data suggest that these compounds behave as agonists. Given that 5-HT1D agonists are currently being explored for their antimigraine action and that activation of h5-HT1B receptors might be associated with cardiovascular side effects, h5-HT1D-selective agents may offer a new lead for the development of therapeutically efficacious agents.