Abstract
The design, synthesis, and biological evaluation of a series of pyrazolopyridines was carried out. Structural optimization of the aniline moiety of 4-anilinopyrazolopyridine derivative 3a, which is one of the newly discovered chemical leads for PDE4 inhibitors from our in-house library, was performed successfully. The details of the discovery of new orally active PDE4 inhibitors, which are expected to show therapeutic potential, are presented and their structure-activity relationships are discussed. Pharmacological evaluation and pharmacokinetic data for representative compounds are also presented.
MeSH terms
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3',5'-Cyclic-AMP Phosphodiesterases / antagonists & inhibitors*
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Aniline Compounds / chemistry
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Animals
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Biological Assay
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Cyclic Nucleotide Phosphodiesterases, Type 4
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Drug Design
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Ferrets
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Guinea Pigs
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Humans
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Male
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Molecular Structure
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Phosphodiesterase Inhibitors / administration & dosage*
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Phosphodiesterase Inhibitors / chemical synthesis
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Phosphodiesterase Inhibitors / therapeutic use*
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Pyrazoles / administration & dosage*
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Pyrazoles / chemical synthesis
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Pyrazoles / therapeutic use*
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Pyridines / administration & dosage*
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Pyridines / chemical synthesis
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Pyridines / therapeutic use*
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Rats
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Rats, Sprague-Dawley
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Structure-Activity Relationship
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U937 Cells
Substances
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Aniline Compounds
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Phosphodiesterase Inhibitors
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Pyrazoles
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Pyridines
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pyrazolopyridine
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3',5'-Cyclic-AMP Phosphodiesterases
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Cyclic Nucleotide Phosphodiesterases, Type 4
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aniline