title: Design, synthesis, and biological evaluation of new phosphodiesterase type 4 inhibitors.
abstract: The design, synthesis, and biological evaluation of new phosphodiesterase type 4 inhibitors, which possess new templates instead of a cyclohexane ring, are described. The mode of interaction with the enzyme is discussed based on the structure-activity relationship (SAR) data obtained for the synthesized inhibitors. Furthermore, the roles of three pharmacophores, a catechol moiety, a nitrile moiety, and acidic moieties, are discussed using in silico docking studies. More detailed biological evaluations of selected 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: Yoshihiko
authors.initials: Y
authors.lastname: Odagaki
authors.forename: Tazumi
authors.initials: T
authors.lastname: Ohtani
authors.forename: Akiharu
authors.initials: A
authors.lastname: Ishida
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: Kaoru
authors.initials: K
authors.lastname: Kobayashi
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; D001665:Binding Sites; D016084:Bronchoconstriction / Q000187:drug effects; D003198:Computer Simulation; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D005289:Ferrets; D005746:Gastric Emptying / Q000187:drug effects; D006168:Guinea Pigs; D006576:Heterocyclic Compounds, 4 or More Rings / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D020889:Rolipram / Q000737:chemistry; D013329:Structure-Activity Relationship; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D014839:Vomiting / Q000188:drug therapy
chemical_list: D004791:Enzyme Inhibitors; D006576:Heterocyclic Compounds, 4 or More Rings; D014409:Tumor Necrosis Factor-alpha; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; D020889:Rolipram