Toward the development of selective cyclooxygenase-2 inhibitors, a series of pyrrolidine derivatives is described. All the compounds containing sulfonamide, ester, nitrile, acid, amide and urea functionalities were computationally screened, and binding affinity scores for all synthesized compounds with cyclooxygenase-1 and cyclooxygenase -2 were compared. The computational observations showed three top-ranked compounds (8b, 8d and 10a) having selectively more affinity for cyclooxygenase -2. These were selected for pharmacological evaluation using carrageenan-induced rat paw edema model. Compound 8b showed maximum activity (54.83%) which was closer to standard drug indometacin (57.48%). The safety parameter of the potent compound (8b) was assessed using aspirin induced gastric ulceration animal model.