Abstract
A series of 4-anilinopyrazolopyridine derivatives were synthesized and biologically evaluated as inhibitors of phosphodiesterase (PDE4). Chemical modification of 3, a structurally new chemical lead that was found in our in-house library, was focused on 1- and 3-substituents. Full details of the discovery of a new orally active chemical lead 5 are presented. Structure-activity relationship data, pharmacological evaluation, and the subtype selectivity study are also presented.
MeSH terms
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3',5'-Cyclic-AMP Phosphodiesterases / antagonists & inhibitors*
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Animals
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Bronchoconstriction / drug effects
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Cyclic Nucleotide Phosphodiesterases, Type 4
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Ferrets
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Gastric Emptying / drug effects
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Guinea Pigs
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Humans
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Lipopolysaccharides / antagonists & inhibitors
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Male
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Phosphodiesterase Inhibitors / chemical synthesis
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Phosphodiesterase Inhibitors / pharmacology
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Pyrazoles / chemical synthesis*
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Pyrazoles / pharmacology
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Pyridines / chemical synthesis*
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Pyridines / pharmacology
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Rats
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Rats, Sprague-Dawley
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SRS-A / pharmacology
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Structure-Activity Relationship
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Tumor Necrosis Factor-alpha / biosynthesis
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Vomiting / chemically induced
Substances
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Lipopolysaccharides
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Phosphodiesterase Inhibitors
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Pyrazoles
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Pyridines
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SRS-A
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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