Discovery of a New class of potent MMP inhibitors by structure-based optimization of the arylsulfonamide scaffold

M Mori, A Massaro, V Calderone, M Fragai…

Index: Mori, Mattia; Massaro, Assunta; Calderone, Vito; Fragai, Marco; Luchinat, Claudio; Mordini, Alessandro ACS Medicinal Chemistry Letters, 2013 , vol. 4, # 6 p. 565 - 569

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Citation Number: 9

Abstract

A new class of potent matrix metalloproteinase (MMP) inhibitors designed by structure- based optimization of the well-known arylsulfonamide scaffold is presented. Molecules show an ethylene linker connecting the sulfonamide group with the P1′ aromatic portion and a d- proline residue bearing the zinc-binding group. The affinity improvement provided by these modifications led us to discover a nanomolar MMP inhibitor bearing a carboxylate moiety ...

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