Abstract
The synthesis and in vitro antiplatelet activity significant data of coumarin derivatives 5i-x and quinolin-2(1H)-one derivatives 22a,b, as well as the corresponding structure-activity relationships are described. The recently reported 8-methyl-4-(1-piperazinyl)-7-(3-pyridylmethoxy)coumarin 5f and its potent 7-(2-morpholinoethoxy)-substituted new analogue 5u were notably more effective inhibitors of pure human platelet PDE3 than milrinone and cilostazol: these data were related, through a molecular modeling study, with the molecular interactions of the four compounds with the human PDE3A catalytic site.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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3',5'-Cyclic-AMP Phosphodiesterases / antagonists & inhibitors*
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3',5'-Cyclic-AMP Phosphodiesterases / blood
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3',5'-Cyclic-AMP Phosphodiesterases / chemistry
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Catalytic Domain
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Coumarins / chemical synthesis*
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Coumarins / chemistry
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Coumarins / pharmacology
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Cyclic Nucleotide Phosphodiesterases, Type 3
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Humans
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In Vitro Techniques
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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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Phosphodiesterase Inhibitors / chemical synthesis*
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Phosphodiesterase Inhibitors / chemistry
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Phosphodiesterase Inhibitors / pharmacology
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Piperazines / chemical synthesis*
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Piperazines / chemistry
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Piperazines / pharmacology
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Platelet Aggregation Inhibitors / chemical synthesis*
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Platelet Aggregation Inhibitors / chemistry
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Platelet Aggregation Inhibitors / pharmacology
Substances
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8-methyl-4-(1-piperazinyl)-7-(3-pyridylmethoxy)coumarin
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8-methyl-7-(2-morpholinoethoxy)-4-(1-piperazinyl)-2H-1-benzopyran-2-one
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Coumarins
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Morpholines
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Phosphodiesterase Inhibitors
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Piperazines
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Platelet Aggregation Inhibitors
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3',5'-Cyclic-AMP Phosphodiesterases
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Cyclic Nucleotide Phosphodiesterases, Type 3
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PDE3A protein, human