Abstract
G-protein-coupled receptor kinase (GRK)-2 and -5 are emerging therapeutic targets for the treatment of cardiovascular disease. In our efforts to discover novel small molecules to inhibit GRK-2 and -5, a class of compound based on 3-(benzo[d]oxazol-2-yl)-5-(1-(piperidin-4-yl)-1H-pyrazol-4-yl)pyridin-2-amine was identified as a novel hit by high throughput screening campaign. Structural modification of parent benzoxazole scaffolds by introducing substituents on phenyl displayed potent inhibitory activities toward GRK-2 and -5.
Keywords:
Benzoxazole; G-protein-coupled receptor kinase-2 (GRK-2); GRK-5; Heart failure.
Copyright © 2013 Elsevier Ltd. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amines / chemistry*
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Benzoxazoles / chemistry
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Binding Sites
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Catalytic Domain
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Drug Design*
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Enzyme Activation / drug effects
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G-Protein-Coupled Receptor Kinase 2 / antagonists & inhibitors*
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G-Protein-Coupled Receptor Kinase 2 / metabolism
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G-Protein-Coupled Receptor Kinase 5 / antagonists & inhibitors*
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G-Protein-Coupled Receptor Kinase 5 / metabolism
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Molecular Docking Simulation
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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 / metabolism
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Protein Kinase Inhibitors / pharmacology*
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Pyrazoles / chemistry
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Pyridines / chemistry
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Structure-Activity Relationship
Substances
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Amines
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Benzoxazoles
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Protein Kinase Inhibitors
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Pyrazoles
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Pyridines
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pyrazole
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G-Protein-Coupled Receptor Kinase 2
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G-Protein-Coupled Receptor Kinase 5
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pyridine