Aim:To design and synthesize a series of benzenesulfonamide derivatives,4-[2-alkylthio-5(4)-(4-substitutedphenyl)imidazole-4(5)-yl]benzenesulfonamides(4a-4j),which are intended to act as cyclooxygenase-2(COX-2)inhibitors with goodCOX-2 inhibitor activity,and which will exert anti-inflammatory activities in vivo.Methods:Benzenesulfonamide derivatives were designed and synthesized throughmulti-step chemical reactions.All the synthesized compounds were evaluated inan in vitro assay.The active compound 4a-af was selected for further evaluationin a carrageenan-induced rat paw edema model.Results:Docking studies showedthat compound 4 bind into the primary binding site of COX-2 with the sulfonamideSO_2NH_2 moiety interacting with the secondary pocket amino acid residues.In thein vitro assay,compound 4 inhibited COX-2 with an inhibition concentration IC_(50)value of 1.23-8 nmol/L,compared to celecoxib with IC50 value of 1.5 nmol/L.Com-pound 4b and 4c had good potency and selectivity in comparison to the celecoxib.In the in vivo model,compound 4a-4f exhibited a moderate potency to inhibit 50%carrageenan-induced paw edema with value of 1.58-4.3 mg/kg.In the latterexperiment,compound 4c was the most active compound.Conclusion:The anti-inflammatory effects obtained for compound 4a-4j could be due to the presenceof fluorine or hydrogen substituents in the para position of the phenyl ring ofthese compounds. Aim: To design and synthesize a series of benzenesulfonamide derivatives, 4- [2-alkylthio-5 (4) - (4-substitutedphenyl) imidazole- as cyclooxygenase-2 (COX-2) inhibitors with good COX-2 inhibitor activity, and which will exert anti-inflammatory activities in vivo. Methods: Benzenesulfonamide derivatives were designed and synthesized through multi-step chemical reactions. All the synthesized compounds were evaluated inan in vitro assay. The active compound 4a-af was selected for further evaluation in a carrageenan-induced rat paw edema model. Results: Docking studies showed that compound 4 bind into the primary binding site of COX-2 with the sulfonamide SO 2 -NH 2 moiety interacting with the secondary pocket amino acid residues. in the in vitro assay, compound 4 inhibited COX-2 with an inhibition concentration IC 50 value of 1.23-8 nmol / L, compared to celecoxib with IC 50 value of 1.5 nmol / L.Com-pound 4b and 4c had good potency and selectivity in compari son to the celecoxib. the in vivo model, compound 4a-4f exhibited a moderate potency to inhibit 50% carrageenan-induced paw edema with value of 1.58-4.3 mg / kg. in the latterexperiment, compound 4c was the most active compound. Conclusion: The anti-inflammatory effects obtained for compounds 4a-4j could be due to the presence of fluorine or hydrogen substituents in the para position of the phenyl ring of the compounds.