beta-N-Biaryl ether sulfonamide hydroxamates as potent gelatinase inhibitors: part 1. Design, synthesis, and lead identification.

A new series of beta-N-biaryl ether sulfonamide hydroxamates as novel gelatinase inhibitors is described. These compounds exhibit good potency for MMP-2 and MMP-9 without inhibiting MMP-1. The structure-activity relationships (SAR) reveal the biaryl ether type P1' moiety together with methanesulfonamide is the optimal combination that provides inhibitory activity of MMP-9 in the single-digit nanomolar range.