Substituted heterocyclic analogs in the Flosulide class were investigated as potential selective cyclooxygenase-2 inhibitors. 6-(4-Ethyl-2-thiazolylthio)-5-methanesulfonamido-3H-isobe nzofuran-1-one 14 was found to be the optimal compound in the series with superior in vitro and in vivo activities.