Heterocycle-based MMP inhibitors with P2' substituents.

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Pikul S, Dunham KM, Almstead NG, De B, Natchus MG, Taiwo YO, Williams LE, Hynd BA, Hsieh LC, Janusz MJ, Gu F, Mieling GE

Heterocycle-based MMP inhibitors with P2' substituents.

Bioorg Med Chem Lett. 2001 Apr 23;11(8):1009-13.

PubMed ID

11327577 [ View in PubMed

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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.

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
1-Benzyl-3-(4-Methoxy-Benzenesulfonyl)-6-Oxo-Hexahydro-Pyrimidine-4-Carboxylic Acid Hydroxyamide	Stromelysin-1	IC 50 (nM)	3.1	N/A	N/A	Details