Several classes of arylsulfone-based MMP-2/-9 inhibitors utilizing 6-to 8-membered heterocyclic rings as zinc-binding groups (ZBGs) have been synthesized and their enzyme inhibitory activities were evaluated. Although a number of 6-and 7-membered heterocycles were effective, the most potent arylsulfone inhibitors are based on the rigid 1-or 3- hydroxypyridone ZBG.