Abstract
A series of 3-aryl-4-(arylhydrazono)-1H-pyrazol-5-one inhibitors of GSK3beta was developed from a low molecular weight, highly ligand efficient screening hit 1. Hit-to-lead optimization led to a number of highly potent inhibitors, while maintaining the high ligand efficiency of the screening hit.
Copyright 2010 Elsevier Ltd. All rights reserved.
MeSH terms
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Binding Sites
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Crystallography, X-Ray
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Glycogen Synthase Kinase 3 / antagonists & inhibitors*
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Glycogen Synthase Kinase 3 / metabolism
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Glycogen Synthase Kinase 3 beta
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Ligands*
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Protein Binding
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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 Kinases / chemistry
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Protein Kinases / metabolism
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Pyrazolones / chemical synthesis
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Pyrazolones / chemistry*
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Pyrazolones / pharmacology
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Structure-Activity Relationship
Substances
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Ligands
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Protein Kinase Inhibitors
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Pyrazolones
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Protein Kinases
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Glycogen Synthase Kinase 3 beta
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Glycogen Synthase Kinase 3