Abstract
The discovery of 4-morpholino-pyrimidin-6-one and 4-morpholino-pyrimidin-2-one-containing inhibitors of Phosphoinositide 3-kinases (PI3K) p110β isoform is reported. Structure-based optimisation of the original fragment hit resulted in lead compounds with improvements in ligand efficiency, lipophilicity efficiency, p110β potency and selectivity over p110α.
Copyright © 2012 Elsevier Ltd. All rights reserved.
MeSH terms
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Drug Discovery*
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Enzyme Activation / drug effects
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Enzyme Inhibitors / chemistry*
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Enzyme Inhibitors / pharmacology
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Inhibitory Concentration 50
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Models, Molecular
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Morpholines / chemical synthesis
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Morpholines / chemistry
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Morpholines / pharmacology
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Peptide Fragments / chemical synthesis
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Peptide Fragments / chemistry
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Peptide Fragments / pharmacology
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Phosphoinositide-3 Kinase Inhibitors*
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Protein Binding / drug effects
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Protein Isoforms / antagonists & inhibitors
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Pyrimidinones / chemical synthesis
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Pyrimidinones / chemistry
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Pyrimidinones / pharmacology
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Solubility
Substances
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Enzyme Inhibitors
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Morpholines
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Peptide Fragments
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Phosphoinositide-3 Kinase Inhibitors
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Protein Isoforms
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Pyrimidinones