Matrix metalloproteinase inhibitors containing a (carboxyalkyl)amino zinc ligand: Modification of the P1 and P2' residues

Article abstract of DOI:10.1021/jm00031a018

Systematic modification of the presumed P1 side chain in a series of (carboxyalkyl)amino-based inhibitors of matrix metalloproteinases enabled identification of the 2-(1,3-dihydro-1,3-dioxo-2H-benz[f]isoindol-2-yl)ethyl group as a preferred substituent imparting potent inhibition of the enzymes collagenase and gelatinase. It was subsequently found that the P2'-P3' residues in this series could be replaced by small non-peptide residues, while maintaining inhibitory potency. The imide group in this series of compounds can undergo autocatalytic hydrolysis under neutral conditions.