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

• Published in: Bioorganic & medicinal chemistry 2008, Vol.16 (1), p.276-283
• Main Authors: Gadad, Andanappa K., Palkar, Mahesh B., Anand, K., Noolvi, Malleshappa N., Boreddy, Thippeswamy S., Wagwade, J.
• Format: Article
• Language: English
• Subjects: Animals; Anti-inflammatory activity; Anti-Inflammatory Agents - chemistry; Anti-Inflammatory Agents - pharmacology; Biological and medical sciences; Bones, joints and connective tissue. Antiinflammatory agents; Cyclooxygenase; Cyclooxygenase 2 Inhibitors - chemical synthesis; Cyclooxygenase 2 Inhibitors - pharmacology; Cyclooxygenase Inhibitors; Edema; Imidazo[2,1- b]-1,3,4-thiadiazoles; Inflammation - drug therapy; Medical sciences; Molecular Structure; NSAIDs; Pharmacology. Drug treatments; Rats; Spectrum Analysis; Thiadiazoles - chemical synthesis; Thiadiazoles - pharmacology
• ISSN: 0968-0896; 1464-3391
• DOI: 10.1016/j.bmc.2007.09.038

A series of 2-trifluoromethyl/sulfonamido-5,6-diarylsubstituted 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 α-bromo-1,2-( p-substituted)diaryl-1-ethanones 13a– h. Structures of these compounds were established by IR, 1H NMR, 13C NMR, Mass, and HRMS data. The selected compounds were evaluated for their preliminary in vitro cyclooxygenase inhibitory activity against COX-2 and COX-1enzymes 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.