Abstract
A series of aminopyrazines as inhibitors of Syk kinase activity and showing inhibition of LAD2 cells degranulation is described. Optimization of the carboxamide motif with aminomethylpiperidines provided high potency inhibiting Syk but low cellular activity. Amides of cis and trans adamantanol showed good inhibitory activity against Syk as well as remarkable activity in LAD2 cells degranulation assay.
Copyright © 2012 Elsevier Ltd. All rights reserved.
MeSH terms
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Adamantane / analogs & derivatives
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Adamantane / chemistry
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Adamantane / pharmacology
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Cell Line, Tumor
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Crystallography, X-Ray
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Enzyme Activation / drug effects
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Enzyme Inhibitors / pharmacology
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Humans
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Inhibitory Concentration 50
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Intracellular Signaling Peptides and Proteins / antagonists & inhibitors*
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Molecular Structure
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Protein-Tyrosine Kinases / antagonists & inhibitors*
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Pyrazines / chemical synthesis*
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Pyrazines / chemistry
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Pyrazines / pharmacology*
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Syk Kinase
Substances
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Enzyme Inhibitors
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Intracellular Signaling Peptides and Proteins
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Pyrazines
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Protein-Tyrosine Kinases
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SYK protein, human
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Syk Kinase
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1-adamantanol
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Adamantane