Powers L J, Fogt S W, Ariyan Z S, Rippin D J, Heilman R D, Matthews R J
J Med Chem. 1981 May;24(5):604-9. doi: 10.1021/jm00137a022.
The effect of structural change on the biological activity of a series of imidazothiazoles and thiazolobenzimidazoles is described. It was found that compounds with polar substituents at the 2 or 3 position of the ring system are less acutely toxic while maintaining antiinflammatory activity. Other structural changes, such as the incorporation of a gem-dimethyl substituent in the 6 position, increase acute toxicity and eliminate antiinflammatory activity. The compound with the best activity/toxicity ratio contains an alkyl sulfonyl substituent on the thiazole ring. The thiazolobenzimidazole analogues are more potent than the imidazole analogues.
描述了结构变化对一系列咪唑并噻唑和噻唑并苯并咪唑生物活性的影响。结果发现，在环系的2位或3位带有极性取代基的化合物急性毒性较小，同时保持抗炎活性。其他结构变化，如在6位引入偕二甲基取代基，会增加急性毒性并消除抗炎活性。活性/毒性比最佳的化合物在噻唑环上含有一个烷基磺酰基取代基。噻唑并苯并咪唑类似物比咪唑类似物更有效。
