A series of 2-alkoxyphenyl methanesulfonamide based compounds were synthesised and evaluated for their anti-inflammatory activity in carrageenan-induced rat paw edema model. The compounds 4–7 showed comparable antiinflammatory activity to rofecoxib and indomethacin, the standard drugs taken in both the studies. The synthesised compounds were also investigated for their gastric ulcerogenic potential and found to be non-ulcerogenic at the test doses. In silico (docking studies) were done to investigate the hypothetical binding mode of the target compounds to the cyclooxygenase isoenzyme (COX-2). A binding model has been proposed based on the docking studies to explain the observed pharmacological activity of the test compounds. Selected physicochemical parameters for the target compounds suggest good drug transport properties and potential bioavailability.