Design, synthesis, activity, and structure of a novel class of matrix metalloproteinase inhibitors containing a heterocyclic P'2-P'3 amide bond isostere

Article abstract of DOI:10.1016/S0960-894X(96)00283-1

A novel series of hydroxamate-based inhibitors of matrix metalloproteinases containing benzimidazole and imidazole heterocycles as amide bond isosteres have been prepared. Potent inhibition (in the low nanomolar 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.