Abstract
A series of pyrazolylpyrimidine scaffold based Syk inhibitors were synthesized and evaluated for their biological activities and selectivity. Lead optimization efforts provided compounds with potent Syk inhibition in both enzymatic and TNF-α release assay.
Keywords:
Pyrazolylpyrimidine; Rheumatoid arthritis; Spleen tyrosine kinase; Structure–activity relationship; Syk inhibitors.
Copyright © 2015 Elsevier Ltd. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Crystallography, X-Ray
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Dogs
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Dose-Response Relationship, Drug
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Humans
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Intracellular Signaling Peptides and Proteins / antagonists & inhibitors*
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Intracellular Signaling Peptides and Proteins / metabolism
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Male
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Models, Molecular
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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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Protein-Tyrosine Kinases / metabolism
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Pyrazoles / chemical synthesis
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Pyrazoles / chemistry
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Pyrazoles / pharmacology*
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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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Rats, Sprague-Dawley
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Structure-Activity Relationship
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Syk Kinase
Substances
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Intracellular Signaling Peptides and Proteins
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Protein Kinase Inhibitors
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Pyrazoles
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Pyrimidines
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pyrazolylpyrimidine
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Protein-Tyrosine Kinases
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SYK protein, human
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Syk Kinase
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Syk protein, rat