DESIGN, SYNTHESIS, ACTIVITY, AND STRUCTURE OF A NOVEL CLASS OF MATRIXMETALLOPROTEINASE INHIBITORS CONTAINING A HETEROCYCLIC P-2'-P-3' AMIDE BOND ISOSTERE

A novel series of hydroxamate-based inhibitors of matrix metalloprotei nases containing benzimidazole and imidazole heterocycles as amide bon d isosteres have been prepared. Potent inhibition (in the low nanomola r range) and selectivity (> 100-fold) can be attained with inhibitors containing only one amide bond. X-ray crystal structures of matrilysin (MMP-7) with two different inhibitors bound confirm that imidazole is an excellent amide bond isostere. Copyright (C) 1996 Elsevier Science Ltd