Synthesis and analgesic activity of 1,3-dihydro-3-(substituted phenyl)imidazo[4,5-b]pyridin-2-ones and 3-(substituted phenyl)-1,2,3-triazolo[4,5-b]pyridines.
Synthesis and analgesic activity of 1,3-dihydro-3-(substituted phenyl)imidazo[4,5-b]pyridin-2-ones and 3-(substituted phenyl)-1,2,3-triazolo[4,5-b]pyridines.
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1,3-二氢-3-(取代苯基)咪唑并[4,5-b]吡啶-2-酮类和3-(取代苯基)-1,2,3-三唑并[4,5-]的合成及镇痛活性
DOI：
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发表时间：
1978
影响因子：
7.3
通讯作者：
L. Flataker
中科院分区：
文献类型：
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作者：
R. L. Clark;A. A. Pessolano;T. Shen;D. Jacobus;H. Jones;V. J. Lotti;L. Flataker
在非甾体镇痛药的研究中，合成了一系列1，3-二氢-3-（取代苯基）咪唑并[4，5-B]吡啶-2-酮和3-（取代苯基）三唑并[4，5-B]吡啶。许多咪唑啉酮在游离氮上被烷基化。在改良的Randall-Selitto镇痛试验中，发炎和正常足的疼痛阈值均升高。这在非甾体类抗炎药中并不常见。活性最高的化合物是1，3-二氢-3-[3，4-（亚甲二氧基）苯基]咪唑并[4，5-B]吡啶-2-酮（I-15）及其N-烯丙基（I-21）和N-异丙基（I-121）衍生物。在三唑类化合物中，以3-（2-氟-和2，4-二氟苯基）三唑并[4，5-B]吡啶（T-1和T-8）为最佳。咪唑类化合物的镇痛活性略上级可待因和d-丙氧芬，但未显示出任何麻醉特性。一些化合物还具有对抗角叉菜胶诱导的大鼠足水肿的活性，因此这些化合物代表了一类新的非麻醉性镇痛抗炎药，能够产生比其他非甾体类抗炎药更大程度的镇痛作用。
In a study of nonsteroidal antiinflammatory and analgesic agents, a series of 1,3-dihydro-3-(substituted phenyl)imidazo[4,5-b]pyridin-2-ones-and 3-(substituted phenyl)triazolo[4,5-b]pyridines was prepared. Many of the imidazolones were alkylated on the free nitrogen. In a modified Randall-Selitto analgesic assay, the pain thresholds of both the inflamed and normal foot were elevated. This is not commonly observed with nonsteroidal antiinflammatory agents. The most active compounds were 1,3-dihydro-3[3,4-(methylenedioxy)phenyl]imidazo[4,5-b]pyridin-2-one (I-15) and its N-allyl (I-21) and N-isopropyl (I-121) derivatives. In the triazole series the 3-(2-fluoro- and 2,4-difluorophenyl)triazolo[4,5-b]pyridines (T-1 and T-8) were the best. The imidazole compounds were somewhat superior in analgesic activity to codeine and d-propoxyphene without showing any narcotic characteristics. Some of the compounds also possessed activity against carrageenan-induced foot edema in the rat, so these compounds represent a new class of nonnarcotic analgesic antiinflammatories, capable of producing a greater degree of analgesia than that obtainable with other nonsteroidal antiinflammatory agents.