Substituted Phenyl acetic acids have been used for the synthesis of various γ-butyrolactone. γ-butyrolactone compounds were designed by docking studies with cycloxygenase II active site. Thirteen compounds of γ-butyrolactone have been synthesized, characterized and subjected for analgesic activity in mice by hot plate method. Some of the compounds have been found to show better hydrogen and hydrophobic interactions with the cyclooxygenase enzyme. Out of 13 compounds 05 compounds have shown significant analgesic activity and can serve as future potential to be active as analgesic agents by inhibiting cyclooxygenase II enzyme. It has been observed that the analgesic activity of the compounds depends on the structure activity relationship of certain functional group. Structure activity relationship studies shows that by introduction of groups like halogens, hydroxyl and methoxy group plays a prominent role in enhancing analgesic activity of the substituted butyrolactones.