12-N-m-Cyanobenzenesulfonyl matrinic butyl methyl ether is a potent anti-coxsackievirus B3（CVB3） agent bearing a novel structure skeleton. Taking this compound as a lead, totally 15 novel target compounds have been synthesized and evaluated for the anti-CVB3 activities using CPE method. Structure- activity relationship（SAR）demonstrated that the shorten-length of 11-side chain was not helpful for keeping the good anti-virus activity. Among the newly synthesized compounds, compound c1 displayed a good anti-CVB3 activity with the IC(50) of 7.1 μmol·L(-1) and SI of 35.5, similar to that of the lead. The SAR results provided useful information for further optimization of these compounds in the molecular structure.