Analogues of capsaicin with agonist activity as novel analgesic agents; structure-activity studies. 3. The hydrophobic side-chain "C-region".
Analogues of capsaicin with agonist activity as novel analgesic agents; structure-activity studies. 3. The hydrophobic side-chain "C-region".
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作为新型镇痛剂的具有激动剂活性的辣椒素类似物；
DOI：
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发表时间：
1993
影响因子：
7.3
通讯作者：
J. Winter
中科院分区：
文献类型：
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作者：
C. Walpole;R. Wrigglesworth;S. Bevan;E. Campbell;A. Dray;I. James;K. J. Masdin;M. Perkins;J. Winter
辣椒素分子疏水侧链（“C区”）的结构变体已被纳入一系列香草酰胺和香草硫脲中。这些化合物已经在体外实验中测试了激动作用（45Ca2+内流到背根神经节神经元），先前显示可以预测镇痛活性。本研究的结果表明，为了获得高效，需要具有有限尺寸的疏水取代基（摩尔折射率，MR, < 55）。本文所获得的辣椒素分子c区信息与前两篇论文所描述的研究相结合，为设计更有效的化合物提供了合理的基础。
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 (45Ca2+ 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.