title: Synthesis and biological evaluation of imidazol-2-one and 2-cyanoiminoimidazole derivatives: novel series of PDE4 inhibitors.
abstract: This communication describes the synthesis and in vitro PDE4 inhibitory activity of a novel series of imidazol-2-one and 2-cyanoiminoimidazole derivatives. The compounds described were also tested in in vivo models to evaluate their anti-inflammatory activity after topical administration as well as their gastro-intestinal side effects. Several compounds proved to be potent PDE4 inhibitors and some 2-cyanoiminoimidazoles showed less pronounced gastro-intestinal side effects than reference compounds but maintained anti-inflammatory activity after topical administration.
authors.affiliation: Janssen-Cilag, Basic Research Centre, Jarama s/n, 45007, Toledo, Spain. iandres@prodes.jnj.com
authors.forename: J Ignacio
authors.initials: JI
authors.lastname: Andrés
authors.forename: José M
authors.initials: JM
authors.lastname: Alonso
authors.forename: Adolfo
authors.initials: A
authors.lastname: Díaz
authors.forename: Javier
authors.initials: J
authors.lastname: Fernández
authors.forename: Laura
authors.initials: L
authors.lastname: Iturrino
authors.forename: Pedro
authors.initials: P
authors.lastname: Martínez
authors.forename: Encarna
authors.initials: E
authors.lastname: Matesanz
authors.forename: Eddy J
authors.initials: EJ
authors.lastname: Freyne
authors.forename: Frederik
authors.initials: F
authors.lastname: Deroose
authors.forename: Gustaaf
authors.initials: G
authors.lastname: Boeckx
authors.forename: Davy
authors.initials: D
authors.lastname: Petit
authors.forename: Gaston
authors.initials: G
authors.lastname: Diels
authors.forename: Anton
authors.initials: A
authors.lastname: Megens
authors.forename: Marijke
authors.initials: M
authors.lastname: Somers
authors.forename: Jean
authors.initials: J
authors.lastname: Van Wauwe
authors.forename: Paul
authors.initials: P
authors.lastname: Stoppie
authors.forename: Marina
authors.initials: M
authors.lastname: Cools
authors.forename: Fred
authors.initials: F
authors.lastname: De Clerck
authors.forename: Danielle
authors.initials: D
authors.lastname: Peeters
authors.forename: Didier
authors.initials: D
authors.lastname: de Chaffoy
mesh_terms: D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors*; D000287:Administration, Topical; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000494:pharmacology; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004427:Ear Diseases / Q000188:drug therapy; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000138:chemical synthesis / Q000494:pharmacology; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage / Q000138:chemical synthesis / Q000494:pharmacology*; D007249:Inflammation / Q000188:drug therapy; D020128:Inhibitory Concentration 50; D051381:Rats; D013329:Structure-Activity Relationship
chemical_list: D000893:Anti-Inflammatory Agents; D004791:Enzyme Inhibitors; D007093:Imidazoles; C117197:imidazolone; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4