title: N-arylrolipram derivatives as potent and selective PDE4 inhibitors.
abstract: Derivatization of rolipram led to the identification of 3-[4-(3-cyclopentyloxy-4-methoxyphenyl)-2-oxo-pyrrolidin-1-yl]-5-( 3- methoxybenzyloxy)-benzoic acid N',N'-dimethylhydrazide (4), a potent and selective inhibitor of PDE4, which inhibits the activation of human leukocytes with pIC50 values in the range of 7.3-7.8, and blocks antigen induced eosinophilia in Brown Norway rats at a dose of 1 mg/kg (i.t.).
authors.affiliation: Respiratory Disease Therapeutic Area, Novartis Horsham Research Center, West Sussex, UK.
authors.forename: E
authors.initials: E
authors.lastname: Bacher
authors.forename: C
authors.initials: C
authors.lastname: Boer
authors.forename: K
authors.initials: K
authors.lastname: Bray-French
authors.forename: F W
authors.initials: FW
authors.lastname: Demnitz
authors.forename: T H
authors.initials: TH
authors.lastname: Keller
authors.forename: L
authors.initials: L
authors.lastname: Mazzoni
authors.forename: T
authors.initials: T
authors.lastname: Müller
authors.forename: C
authors.initials: C
authors.lastname: Walker
mesh_terms: D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors*; D000818:Animals; D018927:Anti-Asthmatic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; D006801:Humans; D007962:Leukocytes / Q000187:drug effects; D010726:Phosphodiesterase Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D011760:Pyrrolidinones / Q000138:chemical synthesis* / Q000494:pharmacology; D051381:Rats; D011914:Rats, Inbred BN; D020889:Rolipram; D013329:Structure-Activity Relationship
chemical_list: D018927:Anti-Asthmatic Agents; D010726:Phosphodiesterase Inhibitors; D011760:Pyrrolidinones; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; D020889:Rolipram