Abstract
Spleen tyrosine kinase is a new promising target for drug discovery to treat human cancer and inflammatory disorders. A series of pyrazolopyrazine-3-amine and pyrazolopyrimidine-3-amine derivatives was designed and synthesized as new spleen tyrosine kinase inhibitors. The efforts yielded compound 6h with promising spleen tyrosine kinase inhibition in both enzymatic and B-lymphoma cell proliferation assays. Additionally, compound 6h dose dependently inhibited the activation of spleen tyrosine kinase signal in human B-cell lymphoma cells. Compound 6h might serve as a lead for further development of new spleen tyrosine kinase inhibitors.
Keywords:
design and synthesis; inhibitors; pyrazolopyrazine-3-amine; pyrazolopyrimidine-3-amine; spleen tyrosine kinase.
© 2016 John Wiley & Sons A/S.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Binding Sites
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Cell Line, Tumor
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Cell Proliferation / drug effects
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Humans
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Molecular Docking Simulation
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Protein Kinase Inhibitors / chemical synthesis
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Protein Kinase Inhibitors / chemistry*
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Protein Kinase Inhibitors / metabolism
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Protein Kinase Inhibitors / toxicity
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Protein Structure, Tertiary
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Pyrazines / chemical synthesis
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Pyrazines / chemistry*
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Pyrazines / metabolism
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Pyrazines / toxicity
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Pyrazoles / chemical synthesis
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Pyrazoles / chemistry*
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Pyrazoles / metabolism
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Pyrazoles / toxicity
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Pyridines / chemical synthesis
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Pyridines / chemistry*
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Pyridines / metabolism
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Pyridines / toxicity
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Signal Transduction / drug effects
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Spleen / enzymology*
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Structure-Activity Relationship
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Syk Kinase / antagonists & inhibitors*
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Syk Kinase / metabolism
Substances
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1-(3-(2H-1,2,3-triazol-2-yl)phenyl)-N-6-(2-aminocyclohexyl)-1H-pyrazolo(3,4-b)pyrazine-3,6-diamine
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Protein Kinase Inhibitors
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Pyrazines
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Pyrazoles
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Pyridines
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pyrazolopyridine
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Syk Kinase