Abstract
The structure-based design and synthesis of isothiazolidinone (IZD) inhibitors of PTP1B containing imidazoles and imidazolines and their modification to interact with the B site of PTP1B are described here. The X-ray crystal structures of 3I and 4I complexed with PTP1B were solved and revealed the inhibitors are interacting extensively with the B site of the enzyme.
MeSH terms
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Crystallography, X-Ray
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Drug Design
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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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Imidazoles / chemical synthesis
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Imidazoles / chemistry*
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Imidazoles / pharmacology*
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Imidazolines / chemical synthesis
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Imidazolines / chemistry
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Imidazolines / pharmacology
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Models, Molecular
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Protein Tyrosine Phosphatase, Non-Receptor Type 1 / antagonists & inhibitors*
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Structure-Activity Relationship
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Thiazoles / chemical synthesis
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Thiazoles / chemistry*
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Thiazoles / pharmacology*
Substances
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Enzyme Inhibitors
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Imidazoles
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Imidazolines
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Thiazoles
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isothiazolidinone
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Protein Tyrosine Phosphatase, Non-Receptor Type 1