Abstract
A series of pyrido[3',2':4,5]furo[3,2-d]pyrimidines (PFP) were synthesized and tested for phosphodiesterase type 4 (PDE4) inhibitory activity, with the potential to treat asthma and chronic obstructive pulmonary disease (COPD). Structure-activity relationships within this series, leading to an increase of potency on the enzyme, is presented. Both gem-dimethylcyclohexyl moieties fused to the pyridine ring and the substitution at the 5 position of the PFP scaffold, proved to be key elements in order to get a high affinity in the enzyme.
Copyright © 2011 Elsevier Masson SAS. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Asthma / drug therapy
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Asthma / enzymology
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Caco-2 Cells
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Cell Membrane Permeability
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Cyclic Nucleotide Phosphodiesterases, Type 4 / metabolism*
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Ferrets
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Humans
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Models, Molecular
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Phosphodiesterase 4 Inhibitors / chemical synthesis
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Phosphodiesterase 4 Inhibitors / chemistry*
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Phosphodiesterase 4 Inhibitors / pharmacokinetics
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Phosphodiesterase 4 Inhibitors / pharmacology*
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Pulmonary Disease, Chronic Obstructive / drug therapy
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Pulmonary Disease, Chronic Obstructive / enzymology
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Pyrimidines / chemical synthesis
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Pyrimidines / chemistry*
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Pyrimidines / pharmacokinetics
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Pyrimidines / pharmacology*
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Structure-Activity Relationship
Substances
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Phosphodiesterase 4 Inhibitors
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Pyrimidines
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Cyclic Nucleotide Phosphodiesterases, Type 4