Design, synthesis and activity evaluation of novel matrix metalloproteinases inhibitors based on the structure of enzyme

A novel inhibitor series for matrix metalloproteinases (MMPs) were designed and synthesized. Using succinate and malonate as zinc binding groups and long hydrophobic substituents to bind with S₁′ pockets, the compounds showed micromolar inhibition and selectivity for MMP-2 over others. And we found a better activity compound. It is a chance to find a better precursor of MMP-2 inhibitors with activity and bioavailability by further optimization of compounds.