4-(2-ethoxyethoxy)-3-methoxybenzyl isothiocyanate | 150059-12-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 4-(2-ethoxyethoxy)-3-methoxybenzyl isothiocyanate
• 英文别名: 4-(1-ethoxyethoxy)-3-methoxybenzyl isothiocyante；1-(1-Ethoxyethoxy)-4-(isothiocyanatomethyl)-2-methoxybenzene
• CAS: 150059-12-4
• 化学式: C₁₃H₁₇NO₃S
• 分子量: 267.349
• InChiKey: JNHGAWVAFXATDC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  18
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  72.1
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  4-(2-ethoxyethoxy)-3-methoxybenzyl isothiocyanate 在 盐酸 作用下， 以 四氢呋喃 、 乙酸乙酯 为溶剂， 反应 0.17h， 生成 3-(4-Hydroxy-3-methoxy-benzyl)-1-methyl-1-octyl-thiourea
  参考文献：
  名称：

  Analogs of capsaicin with agonist activity as novel analgesic agents; structure-activity studies. 3. The hydrophobic side-chain "C-region"

  摘要：

  Structural variants of the hydrophobic side chain (''C region'') of the capsaicin molecule have been incorporated into a series of vanillylamides and vanillylthioureas. These compounds have been tested in an in vitro assay for agonism (Ca-45(2+) influx into dorsal root ganglia neurones), previously shown to be predictive of analgesic activity. The results of this study have established the requirement for a hydrophobic substituent of limited size (molar refractivity, MR, <55) in order to obtain high potency. Combination of the information gained here about the ''C-region'' of the capsaicin molecule with the studies described in the preceding two papers provides a rational basis for the design of compounds of increased potency.

  DOI：

  10.1021/jm00068a016
• 作为产物：
  描述：

  硫光气 、 [4-(1-乙氧基乙氧基)-3-甲氧基苯基]甲胺 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 0.17h， 以25%的产率得到4-(2-ethoxyethoxy)-3-methoxybenzyl isothiocyanate
  参考文献：
  名称：

  Analogs of capsaicin with agonist activity as novel analgesic agents; structure-activity studies. 3. The hydrophobic side-chain "C-region"

  摘要：

  Structural variants of the hydrophobic side chain (''C region'') of the capsaicin molecule have been incorporated into a series of vanillylamides and vanillylthioureas. These compounds have been tested in an in vitro assay for agonism (Ca-45(2+) influx into dorsal root ganglia neurones), previously shown to be predictive of analgesic activity. The results of this study have established the requirement for a hydrophobic substituent of limited size (molar refractivity, MR, <55) in order to obtain high potency. Combination of the information gained here about the ''C-region'' of the capsaicin molecule with the studies described in the preceding two papers provides a rational basis for the design of compounds of increased potency.

  DOI：

  10.1021/jm00068a016

文献信息

• Analogues of Capsaicin with Agonist Activity as Novel Analgesic Agents:  Structure−Activity Studies. 4. Potent, Orally Active Analgesics
  作者：Roger Wrigglesworth、Christopher S. J. Walpole、Stuart Bevan、Elizabeth A. Campbell、Andy Dray、Glyn A. Hughes、Iain James、Kay J. Masdin、Janet Winter

  DOI：10.1021/jm960512h

  日期：1996.1.1

  reported modular approach. These in vitro agonist effects were shown to correlate with analgesic potency in rodent models. Combination of optimal structural features from each of these regions of the capsaicin molecule have led to highly potent agonists (eg., 1b). Evaluation in vivo established that 1b had analgesic properties but poor oral activity, short duration of action, and excitatory side effects

  辣椒素分子激动剂特性所必需的三个区域的结构特征已通过先前报道的模块化方法进行了描述。在啮齿动物模型中，这些体外激动剂作用与镇痛效果相关。辣椒素分子每个这些区域的最佳结构特征的组合导致了高效的激动剂（例如1b）。体内评估表明1b具有镇痛作用，但口服活性差，作用时间短和兴奋性副作用，使该化合物无法进一步开发。初步代谢研究表明，1b的酚部分在体内迅速被葡萄糖醛酸化，为不良的药代动力学提供了可能的解释。随后对酚基团的特定修饰导致化合物2a-j，保留了体外效能。与“母体”苯酚系列相比，该系列的两个代表2a，h的体内概况有很大改善，它们有望用作止痛药。
• Analogs of capsaicin with agonist activity as novel analgesic agents; structure-activity studies. 3. The hydrophobic side-chain "C-region"
  作者：Christopher S. J. Walpole、Roger Wrigglesworth、Stuart Bevan、Elizabeth A. Campbell、Andy Dray、Iain F. James、Kay J. Masdin、Martin N. Perkins、Janet Winter

  DOI：10.1021/jm00068a016

  日期：1993.8

  Structural variants of the hydrophobic side chain (''C region'') of the capsaicin molecule have been incorporated into a series of vanillylamides and vanillylthioureas. These compounds have been tested in an in vitro assay for agonism (Ca-45(2+) influx into dorsal root ganglia neurones), previously shown to be predictive of analgesic activity. The results of this study have established the requirement for a hydrophobic substituent of limited size (molar refractivity, MR, <55) in order to obtain high potency. Combination of the information gained here about the ''C-region'' of the capsaicin molecule with the studies described in the preceding two papers provides a rational basis for the design of compounds of increased potency.