Abstract
A novel series of highly selective JNK inhibitors based on the 4-quinolone scaffold was designed and synthesized. Structure based drug design was utilized to guide the compound design as well as improvements in the physicochemical properties of the series. Compound (13c) has an IC(50) of 62/170 nM for JNK1/2, excellent kinase selectivity and impressive efficacy in a rodent asthma model.
Published by Elsevier Ltd.
MeSH terms
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4-Quinolones / chemical synthesis
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4-Quinolones / chemistry
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4-Quinolones / pharmacology*
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Crystallography, X-Ray
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Dose-Response Relationship, Drug
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Drug Discovery*
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Humans
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JNK Mitogen-Activated Protein Kinases / antagonists & inhibitors*
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JNK Mitogen-Activated Protein Kinases / metabolism
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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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Structure-Activity Relationship
Substances
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4-Quinolones
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Protein Kinase Inhibitors
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JNK Mitogen-Activated Protein Kinases