In order to find antibacterial candidate compounds, on the basis of previous studies, (E)- 2-hydroxy-3-isopentenyl-4-methoxy cinnamic acid (intermediate I) was synthesized through the hydrolysis of osthole under sodium methoxide/ethanol conditions, Then, seventeen target compounds were designed and synthesized by condensation of intermediate I with different amines. The compounds were confirmed by 1HNMR, 13CNMR and MS. The results of antibacterial activities in vitro showed that the derivatives with simplified structure had better antibacterial activities. Among them, the activities of compounds IIh and IIp were the most prominent. The minimum inhibitory concentration (MIC) of the former to S. aureus and MRSA were 16 mg/L and 32 mg/L, respectively. The MIC of the latter to S. aureus and MRSA of were 8 mg/L and 16 mg/L, respectively. The anti-S. aureus activity of the two compounds were close to that of oxacillin, and the anti-MRSA activity were much better than that of oxacillin. It is worth further structural optimization and in-depth study.