Syntheses and in vitro evaluation of arylsulfone-based MMP inhibitors with heterocycle-derived zinc-binding groups (ZBGs)

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.

Graphical abstractSeveral 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. The most potent arylsulfone inhibitors are based on the rigid 1- or 3-hydroxypyridone ZBG.Figure optionsDownload full-size imageDownload as PowerPoint slide