MATRIX METALLOPROTEINASE INHIBITORS CONTAINING A (CARBOXYALKYL)AMINO ZINC LIGAND - MODIFICATION OF THE P1 AND P2' RESIDUES

Systematic modification of the presumed P1 side chain in a series of ( carboxyalkyl)amino-based inhibitors of matrix metalloproteinases enabl ed identification of the 2-(1,3-dihydro-1,3-dioxo-2H-benz [f] isoindol -2-yl)ethyl group as a preferred substituent imparting potent inhibiti on of the enzymes collagenase and gelatinase. It was subsequently foun d 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.