title: Synthesis and biological activities of 1-pyridylisoquinoline and 1-pyridyldihydroisoquinoline derivatives as PDE4 inhibitors.
abstract: A novel series of 1-pyridylisoquinoline and 1-pyridyldihydroisoquinoline derivatives has been prepared. These compounds showed potent PDE4 inhibitory activities and a broad margin between the K(i) value of the rolipram binding affinity and the IC(50) value of PDE4 inhibition. They also exhibited potent inhibitory activities toward LPS-induced TNF-alpha production in mice.
authors.affiliation: Discovery Research Laboratory, Tanabe Seiyaku Co., Ltd., 3-16-89, Kashima, Yodogawa, 532-8505, Osaka, Japan. t-ukita@tanabe.co.jp
authors.forename: Tatsuzo
authors.initials: T
authors.lastname: Ukita
authors.forename: Masakatsu
authors.initials: M
authors.lastname: Sugahara
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Terakawa
authors.forename: Tooru
authors.initials: T
authors.lastname: Kuroda
authors.forename: Kazuteru
authors.initials: K
authors.lastname: Wada
authors.forename: Aya
authors.initials: A
authors.lastname: Nakata
authors.forename: Hideo
authors.initials: H
authors.lastname: Kikkawa
authors.forename: Katsuo
authors.initials: K
authors.lastname: Ikezawa
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Naito
mesh_terms: D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors*; D000818:Animals; D001667:Binding, Competitive / Q000187:drug effects; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; D004305:Dose-Response Relationship, Drug; D007202:Indicators and Reagents; D007546:Isoquinolines / Q000138:chemical synthesis; D007700:Kinetics; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors / Q000494:pharmacology; D051379:Mice; D010726:Phosphodiesterase Inhibitors / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology*; D011804:Quinolines / Q000138:chemical synthesis; D020889:Rolipram / Q000378:metabolism; D013237:Stereoisomerism; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D007202:Indicators and Reagents; D007546:Isoquinolines; D008070:Lipopolysaccharides; D010726:Phosphodiesterase Inhibitors; D011804:Quinolines; D014409:Tumor Necrosis Factor-alpha; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; D020889:Rolipram