Abstract
The synthesis and the phosphodiesterase-4 (PDE4) inhibitory activity of 2-pyridinemethanol derivatives is described. The evaluation of the structure-activity relationship (SAR) in this series of novel PDE4 inhibitors led to the identification of compound 9 which exhibits excellent in vitro activity, desirable pharmacokinetic parameters and good efficacy in animal models of bronchoconstriction.
MeSH terms
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3',5'-Cyclic-AMP Phosphodiesterases / antagonists & inhibitors*
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Administration, Oral
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Animals
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Biological Availability
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Cyclic Nucleotide Phosphodiesterases, Type 4
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Half-Life
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Humans
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Inhibitory Concentration 50
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Phosphodiesterase Inhibitors / chemical synthesis
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Phosphodiesterase Inhibitors / chemistry*
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Phosphodiesterase Inhibitors / pharmacokinetics
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Phosphodiesterase Inhibitors / pharmacology*
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Picolines / chemical synthesis
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Picolines / chemistry*
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Picolines / pharmacokinetics
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Picolines / pharmacology*
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Rats
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Saimiri
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Stereoisomerism
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Structure-Activity Relationship
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Tumor Necrosis Factor-alpha / antagonists & inhibitors
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Tumor Necrosis Factor-alpha / biosynthesis
Substances
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Phosphodiesterase Inhibitors
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Picolines
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Tumor Necrosis Factor-alpha
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3',5'-Cyclic-AMP Phosphodiesterases
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Cyclic Nucleotide Phosphodiesterases, Type 4