Effect of structural change on acute toxicity and antiinflammatory activity in a series of imidazothiazoles and thiazolobenzimidazoles.
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.
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000138:chemical synthesis*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis; D001169:Arthritis, Experimental / Q000188:drug therapy; D055598:Chemical Phenomena; D002621:Chemistry; D007093:Imidazoles / Q000138:chemical synthesis* / Q000494:pharmacology; D007928:Lethal Dose 50; D008124:Locomotion / Q000187:drug effects; D008297:Male; D051379:Mice; D009129:Muscle Tonus / Q000187:drug effects; D009420:Nervous System / Q000187:drug effects; D009949:Orientation / Q000187:drug effects; D051381:Rats; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000138:chemical synthesis* / Q000494:pharmacology
D000893:Anti-Inflammatory Agents; D000894:Anti-Inflammatory Agents, Non-Steroidal; D007093:Imidazoles; D013844:Thiazoles