pyrazolopyridine and aniline

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.

Topics: 3',5'-Cyclic-AMP Phosphodiesterases; Aniline Compounds; Animals; Biological Assay; Cyclic Nucleotide Phosphodiesterases, Type 4; Drug Design; Ferrets; Guinea Pigs; Humans; Male; Molecular Structure; Phosphodiesterase Inhibitors; Pyrazoles; Pyridines; Rats; Rats, Sprague-Dawley; Structure-Activity Relationship; U937 Cells