Janusz J M, Buckwalter B L, Young P A, LaHann T R, Farmer R W, Kasting G B, Loomans M E, Kerckaert G A, Maddin C S, Berman E F
Procter & Gamble Company, Miami Valley Laboratories, Cincinnati, Ohio 45239-8707.
J Med Chem. 1993 Sep 3;36(18):2595-604. doi: 10.1021/jm00070a002.
As part of a program to establish structure-activity relationships for vanilloids, analogs of the pungent principle capsaicin, the alkyl chain portion of the parent structure (and related compounds derived from homovanillic acid) was varied. In antinociceptive and antiinflammatory assays (rat and mouse hot plate and croton oil-inflamed mouse ear), compounds with widely varying alkyl chain structures were active. Short-chain compounds were active by systemic administration in the assays mentioned above but they retained the high pungency and acute toxicity characteristic of capsaicin. In contrast, the long chain cis-unsaturates, NE-19550 (vanillyloleamide) and NE-28345 (oleylhomovanillamide), were orally active, less pungent, and less acutely toxic than capsaicin. The potential of these compounds as antiinflammatory/analgesic agents is discussed in light of recent data on the mechanism of action of vanilloids on sensory nerve fibers.
作为建立香草酸类构效关系项目的一部分，对辛辣成分辣椒素的类似物、母体结构的烷基链部分（以及源自高香草酸的相关化合物）进行了改变。在抗伤害感受和抗炎试验（大鼠和小鼠热板试验以及巴豆油致炎的小鼠耳部试验）中，具有广泛不同烷基链结构的化合物具有活性。短链化合物通过上述试验中的全身给药具有活性，但它们保留了辣椒素的高辛辣度和急性毒性特征。相比之下，长链顺式不饱和化合物NE - 19550（香草基油酰胺）和NE - 28345（油基高香草酰胺）口服具有活性，比辣椒素刺激性小且急性毒性低。根据最近关于香草酸类对感觉神经纤维作用机制的数据，讨论了这些化合物作为抗炎/镇痛药的潜力。
