Abstract
Synthetic 2-morpholinochromones, including the known PI3-kinase inhibitor LY294002, have been evaluated in vitro as inhibitors of isolated human platelet phosphodiesterases. Inhibition of the cAMP-phosphodiesterases, PDE2 and PDE3 by LY294002 is reported for the first time. Preliminary screening across a range of 2-morpholinochromones has revealed structural features for optimised PDE2 inhibition.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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3',5'-Cyclic-AMP Phosphodiesterases / chemistry
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Blood Platelets / enzymology
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Chromones / pharmacology*
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Cyclic Nucleotide Phosphodiesterases, Type 2
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Cyclic Nucleotide Phosphodiesterases, Type 3
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Dose-Response Relationship, Drug
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Humans
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Morpholines / pharmacology*
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Phosphodiesterase Inhibitors / chemical synthesis
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Phosphodiesterase Inhibitors / pharmacology
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Phosphoinositide-3 Kinase Inhibitors
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Phosphoric Diester Hydrolases / chemistry*
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Structure-Activity Relationship
Substances
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Chromones
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Morpholines
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Phosphodiesterase Inhibitors
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Phosphoinositide-3 Kinase Inhibitors
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2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
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Phosphoric Diester Hydrolases
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3',5'-Cyclic-AMP Phosphodiesterases
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Cyclic Nucleotide Phosphodiesterases, Type 2
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Cyclic Nucleotide Phosphodiesterases, Type 3
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PDE2A protein, human