Preparation and antiarthritic and analgesic activity of 4,5-diaryl-2-(substituted thio)-1H-imidazoles and their sulfoxides and sulfones.
Preparation and antiarthritic and analgesic activity of 4,5-diaryl-2-(substituted thio)-1H-imidazoles and their sulfoxides and sulfones.
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DOI：
10.1021/jm00147a011
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发表时间：
1985-09
影响因子：
7.3
通讯作者：
T. Sharpe;S. Cherkofsky;W. E. Hewes;D. H. Smith;W. A. Gregory;S. Haber;M. Leadbetter;J. G. Whitney
中科院分区：
文献类型：
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作者：
T. Sharpe;S. Cherkofsky;W. E. Hewes;D. H. Smith;W. A. Gregory;S. Haber;M. Leadbetter;J. G. Whitney
合成了一系列4，5-二芳基-2-(取代硫代)-1H-咪唑类化合物，并在大鼠佐剂性关节炎实验和小鼠苯-对苯二酚扭体实验中评价了它们的抗炎和镇痛作用。有几个类似物被发现比苯丁酮和消炎痛更有效。讨论了构效关系。其中一种化合物4，5-bis(4-fluorophenyl)-2-[(1，1，2，2-tetrafluoroethyl)-sulfonyl]-1H-咪唑(8d，替弗拉咪唑)在大鼠佐剂性关节炎试验中的效力是吲哚美辛的8倍，目前正在进行临床试验。
A series of 4,5-diaryl-2-(substituted thio)-1H-imidazoles was synthesized and evaluated as antiinflammatory and analgesic agents in the rat adjuvant induced arthritis assay and the mouse phenyl-p-benzoquinone writhing (PQW) assay. Several analogues were found to be more potent than phenylbutazone and indomethacin. Structure-activity relationships are discussed. One of the compounds, 4,5-bis(4-fluorophenyl)-2-[(1,1,2,2-tetrafluoroethyl)-sulfonyl]-1H- imidazole (8d, tiflamizole), was found to be 8 times as potent as indomethacin in the rat adjuvant induced arthritis assay and is presently undergoing clinical trial as an antiarthritic drug.