Abstract
We have synthesized and evaluated a series of triaryl sulfonamide-based PTP1B inhibitors in which a difluoro-methylenephosphonate group of a potent lead has been replaced by potential bioisosteric replacements. Several mono- or di-charged compounds (8a, 8b, and 15a) were shown exhibit inhibitory activity in the low micromolar range, demonstrating the feasibility of using this approach in identifying non-phosphonate pTyr mimetics in a small molecular scaffold. These results also provide a useful indication of the relative effectiveness of these pTyr mimetics.
MeSH terms
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Enzyme Inhibitors / chemical synthesis*
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Enzyme Inhibitors / chemistry
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Enzyme Inhibitors / pharmacology*
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Fluorine Compounds / chemical synthesis*
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Fluorine Compounds / chemistry
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Fluorine Compounds / pharmacology
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Molecular Structure
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Organophosphorus Compounds / chemical synthesis*
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Organophosphorus Compounds / chemistry
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Organophosphorus Compounds / pharmacology*
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Protein Tyrosine Phosphatase, Non-Receptor Type 1 / antagonists & inhibitors*
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Protein Tyrosine Phosphatase, Non-Receptor Type 1 / metabolism
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Structure-Activity Relationship
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Sulfonamides / chemistry*
Substances
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Enzyme Inhibitors
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Fluorine Compounds
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Organophosphorus Compounds
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Sulfonamides
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Protein Tyrosine Phosphatase, Non-Receptor Type 1