In order to find antibacterial candidate agents. Using fragment based drug discovery methods, fifteen sulfanilamide derivatives were designed and synthesized with aminophosphonate and sulfonyl chloride as raw material. Their structures were confirmed by IR, 1HNMR and 13CNMR. MICs of the target compounds were determined by double dilution method. The results showed that some compounds have potential inhibitory activities against standard bacteria and drug resistant bacteria, the MIC of the compoundⅡf〔N-[（diethoxyphosphonyl -4-fluorobenzyl]-4-methoxybenzenesulfonamide〕 for S.aureus, E. coli, MRSA and MREC was 32, 64, 128, 128μg/mL, respectively, and the MIC of the compoundⅡl 〔N-[（diethoxyphosphonyl -4-fluorobenzyl]-4-fluorobenzenesulfonamide〕was 32, 32, 64, 64μg/mL, respectively. Its antibacterial activities were better than that of the control drug sulfadiazine.