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-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 alpha-bromo-1,2-(p-substituted)diaryl-1-ethanones 13a-h. Structures of these compounds were established by IR, (1)H NMR, (13)C 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.
Gadad
Andanappa K
AK
School of Pharmacy, Faculty of Medical Sciences, The University of the West Indies, St. Augustine, Champs Fleurs, Mount Hope, Trinidad and Tobago. akgadad@rediffmail.com
Palkar
Mahesh B
MB
Anand
K
K
Noolvi
Malleshappa N
MN
Boreddy
Thippeswamy S
TS
Wagwade
J
J
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000737:chemistry* / Q000494:pharmacology; D052246:Cyclooxygenase 2 Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D016861:Cyclooxygenase Inhibitors; D004487:Edema; D007249:Inflammation / Q000188:drug therapy; D015394:Molecular Structure; D051381:Rats; D013057:Spectrum Analysis; D013830:Thiadiazoles / Q000138:chemical synthesis* / Q000494:pharmacology
D000893:Anti-Inflammatory Agents; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D013830:Thiadiazoles