title: New orally active PDE4 inhibitors with therapeutic potential.
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.
authors.affiliation: Minase Research Institute, Ono Pharmaceutical Co. Ltd, 3-1-1 Sakurai, Shimamoto, Mishima, Osaka 618-8585, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ochiai
authors.forename: Akiharu
authors.initials: A
authors.lastname: Ishida
authors.forename: Tazumi
authors.initials: T
authors.lastname: Ohtani
authors.forename: Kensuke
authors.initials: K
authors.lastname: Kusumi
authors.forename: Katuya
authors.initials: K
authors.lastname: Kishikawa
authors.forename: Susumu
authors.initials: S
authors.lastname: Yamamoto
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Takeda
authors.forename: Takaaki
authors.initials: T
authors.lastname: Obata
authors.forename: Hisao
authors.initials: H
authors.lastname: Nakai
authors.forename: Masaaki
authors.initials: M
authors.lastname: Toda
mesh_terms: D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors*; D000814:Aniline Compounds / Q000737:chemistry; D000818:Animals; D001681:Biological Assay; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; D015195:Drug Design; D005289:Ferrets; D006168:Guinea Pigs; D006801:Humans; D008297:Male; D015394:Molecular Structure; D010726:Phosphodiesterase Inhibitors / Q000008:administration & dosage* / Q000138:chemical synthesis / Q000627:therapeutic use*; D011720:Pyrazoles / Q000008:administration & dosage* / Q000138:chemical synthesis / Q000627:therapeutic use*; D011725:Pyridines / Q000008:administration & dosage* / Q000138:chemical synthesis / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013329:Structure-Activity Relationship; D020298:U937 Cells
chemical_list: D000814:Aniline Compounds; D010726:Phosphodiesterase Inhibitors; D011720:Pyrazoles; D011725:Pyridines; C118531:pyrazolopyridine; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; C023650:aniline