Potent matrix metalloproteinase inhibitors: Amino-carboxylate compounds containing modifications of the P1 residue

A series of amino-carboxylate inhibitors of matrix metalloproteinases containing different P1 modifications have been synthesized. It was discovered that a toluenesulfonamide-type substituent at the P1 position considerably enhances the binding affinity of inhibitors for stromelysin. Replacements of the P2′–P3′ residues with nonpeptide components result in loss of inhibitory activity.