Abstract
Quinazoline 3 was discovered as a novel c-jun N-terminal kinase (JNK) inhibitor with good brain penetration and pharmacokinetic (PK) properties. A number of analogs which were potent both in the biochemical and cellular assays were discovered. Quinazoline 13a was found to be a potent JNK3 inhibitor (IC(50)=40 nM), with >500-fold selectivity over p38, and had good PK and brain penetration properties. With these properties, 13a is considered a potential candidate for in vivo evaluation.
Copyright © 2011 Elsevier Ltd. All rights reserved.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Brain / metabolism
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Inhibitory Concentration 50
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JNK Mitogen-Activated Protein Kinases / antagonists & inhibitors*
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Protein Kinase Inhibitors / chemical synthesis*
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Protein Kinase Inhibitors / chemistry
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Protein Kinase Inhibitors / pharmacokinetics
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Protein Kinase Inhibitors / pharmacology*
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Quinazolines / chemical synthesis*
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Quinazolines / chemistry
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Quinazolines / pharmacokinetics
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Quinazolines / pharmacology*
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Structure-Activity Relationship
Substances
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Protein Kinase Inhibitors
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Quinazolines
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JNK Mitogen-Activated Protein Kinases