Microwave Assisted Synthesis, Pharmacological Activities, and Molecular Docking Studies of Ethyl 2-[2-substituted-4-(thiophenyl)thiazolyl] acetates

A series of ethyl 2-[2-arylamino-4-(thiophen-2-yl)thiazol-5-yl] acetates (5a-5k) and ethyl 2-[2-(arylhydrazino)-4-(thiophen-2-yl)thiazol-5-yl] acetates (9a-9g) were synthesized and screened for their anti-inflammatory, analgesic, and antioxidant activities. In vivo test results showed that the compounds with halogen substitution (5c, 5g, 5h, 5i and 5j) at the para position on the 2-aryl amino group exhibited good anti-inflammatory and analgesic activities, similar to that of indomethacin and aspirin, respectively. The ethyl 2-[2-(arylhydrazino)-4-(thiophen-2-yl)thiazol-5-yl] acetates (9a-9g) showed better anti-oxidant activity than compounds 5a-5k, comparable to ascorbic acid. However, these compounds showed moderate to weak anti-inflammatory and analgesic activities. Further, a molecular docking study was performed to predict the possible binding modes on cyclooxygenase-1 (COX-1) and COX-2 for the tested compounds. Good correlation was observed between the anti-inflammatory activity of the compounds and the results of the binding modes in COX-2.