Abstract
A series of SYK inhibitors based on the phenylamino pyrimidine thiazole lead 4 were prepared and evaluated for biological activity. Lead optimization provided compounds with nanomolar K(i)'s against SYK and potent inhibition in mast cell degranulation assays.
MeSH terms
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Animals
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Combinatorial Chemistry Techniques
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Crystallography, X-Ray
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Drug Design
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Intracellular Signaling Peptides and Proteins / antagonists & inhibitors*
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Mast Cells / drug effects
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Microsomes, Liver / drug effects
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Molecular Conformation
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Molecular Structure
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Protein Kinase Inhibitors / chemical synthesis*
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Protein Kinase Inhibitors / chemistry
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Protein Kinase Inhibitors / pharmacology*
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Protein-Tyrosine Kinases / antagonists & inhibitors*
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Pyrimidines / chemical synthesis*
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Pyrimidines / chemistry
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Pyrimidines / pharmacology*
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Rats
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Spleen / enzymology*
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Structure-Activity Relationship
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Syk Kinase
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Thiazoles / chemical synthesis*
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Thiazoles / chemistry
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Thiazoles / pharmacology*
Substances
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Intracellular Signaling Peptides and Proteins
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Protein Kinase Inhibitors
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Pyrimidines
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Thiazoles
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Protein-Tyrosine Kinases
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Syk Kinase
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Syk protein, rat