N-(4-hydroxy-3-methoxybenzyl)-N'-<(4-chlorophenyl)ethyl>thiourea

• 分子结构分类: 有机化合物 - 苯类化合物 - 酚类
• 英文名称: N-(4-hydroxy-3-methoxybenzyl)-N'-<(4-chlorophenyl)ethyl>thiourea
• 英文别名: 1-[2-(4-Chlorophenyl)ethyl]-3-[(4-hydroxy-3-methoxyphenyl)methyl]thiourea
• 化学式: C₁₇H₁₉ClN₂O₂S
• 分子量: 350.869
• InChiKey: KDXZRBCUTLWBGQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  23
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  85.6
• 氢给体数：
  3
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  2-(4-氯苯基)乙基 异硫代氰酸酯 、 香兰素胺盐酸盐 在 sodium hydroxide 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以48%的产率得到N-(4-hydroxy-3-methoxybenzyl)-N'-<(4-chlorophenyl)ethyl>thiourea
  参考文献：
  名称：

  具有激动剂活性的辣椒素类似物作为新型镇痛药的类似物：结构活性研究。4.有力的口服活性止痛药。

  摘要：

  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。

  DOI：

  10.1021/jm960512h

文献信息

• The Discovery of Capsazepine, the First Competitive Antagonist of the Sensory Neuron Excitants Capsaicin and Resiniferatoxin
  作者：Christopher S. J. Walpole、Stuart Bevan、Guenter Bovermann、Johann J. Boelsterli、Robin Breckenridge、John W. Davies、Glyn A. Hughes、Iain James、Lukas Oberer、Janet Winter、Roger Wrigglesworth

  DOI：10.1021/jm00039a006

  日期：1994.6.1

  Capsaicin and resiniferatoxin are natural products which act specifically on a subset of primary afferent sensory neurons to open a novel cation-selective ion channel in the plasma membrane. These sensory neurons are involved in nociception, and so, these agents are targets for the design of a novel class of analgesics. Although synthetic agonists at the capsaicin receptor have been described previously, competitive antagonists at this receptor would be interesting and novel pharmacological agents. Structure-activity relationships for capsaicin agonists have previously been rationalized, by ourselves and others, by dividing the capsaicin molecule into three regions-the A (aromatic ring)-, B (amide bond)-, and C (hydrophobic side chain)-regions. In this study, the effects on biological activity of conformational constraint of the A-region with respect to the B-region are discussed. Conformational constraint was achieved by the introduction of saturated ring systems of different sizes. The resulting compounds provided agonists of comparable potency to unconstrained analogues as well as a moderately potent antagonist, capsazepine. This compound is the first competitive antagonist of capsaicin and resiniferatoxin to be described and is active in various systems, in vitro and in vivo. It has recently attracted considerable interest as a tool for dissecting the mechanisms by which capsaicin analogues evoke their effects. NMR spectroscopy and X-ray crystallography experiments, as well as molecular modeling techniques, were used to study the conformational behavior of a representative constrained agonist and antagonist. The conformation of the saturated ring contraint in the two cases was found to differ markedly, dramatically affecting the relative disposition of the A-ring and B-region pharmacophores. In agonist structures, the A- and B-regions were virtually coplanar in contrast to those in the antagonist, in which they were approximately orthogonal. A rationale for agonist and antagonist activity at the capsaicin receptor is proposed, based on the consideration of these conformational differences.