Walpole C S, Wrigglesworth R, Bevan S, Campbell E A, Dray A, James I F, Masdin K J, Perkins M N, Winter J
Sandoz Institute for Medical Research, Gower Place, London, England.
J Med Chem. 1993 Aug 6;36(16):2381-9. doi: 10.1021/jm00068a016.
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.
辣椒素分子疏水侧链（“C区域”）的结构变体已被纳入一系列香草酰胺和香草基硫脲中。这些化合物已在体外试验中进行了激动作用测试（45Ca2+流入背根神经节神经元），此前已证明该测试可预测镇痛活性。这项研究的结果确定了需要有限大小的疏水取代基（摩尔折射度，MR，<55）才能获得高效能。将此处获得的有关辣椒素分子“C区域”的信息与前两篇论文中描述的研究相结合，为设计高效能化合物提供了合理依据。
