title: Discovery of new orally active phosphodiesterase (PDE4) inhibitors.
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.
authors.affiliation: Minase Research Institute, Ono Pharmaceutical Co., Ltd., 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*; D000818:Animals; D016084:Bronchoconstriction / Q000187:drug effects; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; D005289:Ferrets; D005746:Gastric Emptying / Q000187:drug effects; D006168:Guinea Pigs; D006801:Humans; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors; D008297:Male; D010726:Phosphodiesterase Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology; D011720:Pyrazoles / Q000138:chemical synthesis* / Q000494:pharmacology; D011725:Pyridines / Q000138:chemical synthesis* / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013189:SRS-A / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D014839:Vomiting / Q000139:chemically induced
chemical_list: D008070:Lipopolysaccharides; D010726:Phosphodiesterase Inhibitors; D011720:Pyrazoles; D011725:Pyridines; D013189:SRS-A; D014409:Tumor Necrosis Factor-alpha; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4