Diclofenac sodium is being used for the treatment of pain and inflammation. But as all the NSAIDs are suffering from severe GI toxicities, Diclofenac sodium is also not an exception to these toxocities. The GI toxicity associated with all traditional NSAIDs is mainly due to the presence of free carboxylic group. In the present research work, the main motto was to develop some new heterocyclic analogues of diclofenac as potential analgesic and anti-inflammatory agents with negligible ulcerogenicity. In this paper various heterocyclic analogues of diclofenac were designed by replacing the free –COOH with some less acidic heterocycles and evaluated for COX-1, COX-2 and LTA4 hydrolase binding ability by molecular docking. The most potent ligands were selected as the lead and structural modifications were done to the selected lead compounds in order to increase the potency. Finally these potent ligands were synthesized and characterized by FTIR and 1HNMR. Furthermore the synthesized compounds were also tested for their analgesic, anti-inflammatory and ulcerogenicity activities. Out of all the synthesized compounds, 6 new compounds were found to have significant analgesic and anti-inflammatory activities with negligible ulcerogenicity.