Synthesis and biological evaluation of 2-trifluoromethyl/sulfonamido-5,6-diaryl substituted imidazo[2,1-b]-1,3,4-thiadiazoles:: A novel class of cyclooxygenase-2 inhibitors

A series of 2-trifluoromethyl/sulfonamido-5,6-diaryl substituted imidazo[2,1-b]-1,3,4-thiadiazole derivatives 15a-j have been synthesized by the reaction of 2-amino-5-trifluoromethyl/sulfonamido-1,3,4-thiadiazoles 14a-b and appropriately substituted alpha-bromo-1,2-(p-substituted)diaryl-l-ethanones 13a-h. Structures of these compounds were established by IR, H-1 NMR, C-13 NMR, Mass, and HRMS data. The selected compounds were evaluated for their preliminary in vitro cyclooxygenase inhibitory activity against COX-2 and COX-lenzymes using colorimetric method. The compounds tested showed selective inhibitory activity toward COX-2 (80.6-49.4%) over COX-1 (30.6-8.6), amongst them compounds 15f and 15j showed appreciable COX-2 selective inhibitory activity. These compounds also exhibited significant anti-inflammatory activity (70.09-42.32%), which is comparable to that of celecoxib in the carrageenan-induced rat paw edema method. (c) 2007 Elsevier Ltd. All rights reserved.