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

…, Y Zhang, S Hammond, N Dewdney, T Ho, X Lin…

Index: Chen, Jian Jeffrey; Zhang, Yiping; Hammond, Scott; Dewdney, Nolan; Ho, Teresa; Lin, Xiaohong; Browner, Michelle F.; Castelhano, Arlindo L. Bioorganic and Medicinal Chemistry Letters, 1996 , vol. 6, # 13 p. 1601 - 1606

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Citation Number: 42

Abstract

A novel series of hydrozamate-based inhibitors of matrix metalloproteinases containing benzimidazole and imidazole heterocyles 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 ...