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ID: ALA1134017
Journal: Bioorg Med Chem Lett
Title: Heterocycle-based MMP inhibitors with P2' substituents.
Authors: Pikul S, Dunham KM, Almstead NG, De B, Natchus MG, Taiwo YO, Williams LE, Hynd BA, Hsieh LC, Janusz MJ, Gu F, Mieling GE.
Abstract: Potent and selective inhibition of matrix metalloproteinases was demonstrated for a series of sulfonamide-based hydroxamic acids. The design of the heterocyclic sulfonamides incorporates a six- or seven-member central ring with a P2' substituent that can be modified. Binding interactions of this substituent at the S2' site are believed to contribute to high inhibitory potency against stromelysin, collagenase-3 and gelatinases A and B, and to provide selectivity against collagenase-1 and matrilysin. An X-ray structure of a stromelysin inhibitor complex was obtained to provide insights into the SAR and selectivity trends observed for the series.
CiteXplore: 11327577