Some pyrazinamide derivatives I (n = 1, 2, 3; X = S, NH, O, etc.) were synthesized and evaluated as antimycobacterial agents against Mycobacterium tuberculosis H37Rv strain.These pyrazinamide derivatives were designed by structural modification of pyrazinamide with alkyl chains and six-membered hetereocylic rings, resp.The title pyrazinamide derivatives I were synthesized using pyrazinamide as the starting material for haloakylation, and then halo-alkylpyrazinamides II were reacted with appropriate heterocyclic rings.The activity of pyrazinamide derivatives I was assayed using microplate alamar blue assay (MABA) and characterized by min. inhibitory concentrations (MICs).Results showed that the obtained pyrazinamide derivatives I exhibited high inhibitory effect on M. tuberculosis.The antimycobacterial activity of pyrazinamide derivatives I (n = 2; X = NH, O, S) was the best among all compounds tested, and their MIC values were about 6.25 mμ/mL.These compounds have ethylene chain between pyrazinamide moiety and six-membered hetereocylic rings.