Abstract
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.
MeSH terms
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Animals
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Drug Design
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Gelatinases / antagonists & inhibitors*
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Humans
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Hydroxamic Acids / chemical synthesis*
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Hydroxamic Acids / chemistry
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Hydroxamic Acids / pharmacology*
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Matrix Metalloproteinase Inhibitors*
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Microsomes, Liver / drug effects
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Molecular Structure
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Pyrazines / chemical synthesis*
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Pyrazines / chemistry
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Pyrazines / pharmacology*
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Rats
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Structure-Activity Relationship
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Sulfonamides / chemical synthesis
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Sulfonamides / chemistry
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Sulfonamides / pharmacology
Substances
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CGS 27023A
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Hydroxamic Acids
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Matrix Metalloproteinase Inhibitors
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Pyrazines
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Sulfonamides
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Gelatinases