title: Potent and selective xanthine-based inhibitors of phosphodiesterase 5.
abstract: Inhibitors of PDE5 are useful therapeutic agents for treatment of erectile dysfunction. A series of novel xanthine derivatives has been identified as potent inhibitors of PDE5, with good levels of selectivity against other PDE isoforms, including PDE6. Studies in the dog indicate excellent oral bioavailability for compound 21.
authors.affiliation: Novartis Institutes of Biomedical Research, Horsham Research Centre, Wimblehurst Road, Horsham, West Sussex RH12 5AB, UK.
authors.forename: Nichola J
authors.initials: NJ
authors.lastname: Arnold
authors.forename: Ruth
authors.initials: R
authors.lastname: Arnold
authors.forename: David
authors.initials: D
authors.lastname: Beer
authors.forename: Gurdip
authors.initials: G
authors.lastname: Bhalay
authors.forename: Stephen P
authors.initials: SP
authors.lastname: Collingwood
authors.forename: Sarah
authors.initials: S
authors.lastname: Craig
authors.forename: Nicholas
authors.initials: N
authors.lastname: Devereux
authors.forename: Mark
authors.initials: M
authors.lastname: Dodds
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Dunstan
authors.forename: Robin A
authors.initials: RA
authors.lastname: Fairhurst
authors.forename: David
authors.initials: D
authors.lastname: Farr
authors.forename: Joseph D
authors.initials: JD
authors.lastname: Fullerton
authors.forename: Angela
authors.initials: A
authors.lastname: Glen
authors.forename: Sylvie
authors.initials: S
authors.lastname: Gomez
authors.forename: Sandra
authors.initials: S
authors.lastname: Haberthuer
authors.forename: Julia D I
authors.initials: JD
authors.lastname: Hatto
authors.forename: Colin
authors.initials: C
authors.lastname: Howes
authors.forename: Darryl
authors.initials: D
authors.lastname: Jones
authors.forename: Thomas H
authors.initials: TH
authors.lastname: Keller
authors.forename: Beate
authors.initials: B
authors.lastname: Leuenberger
authors.forename: Heinz E
authors.initials: HE
authors.lastname: Moser
authors.forename: Irene
authors.initials: I
authors.lastname: Muller
authors.forename: Reto
authors.initials: R
authors.lastname: Naef
authors.forename: Paul A
authors.initials: PA
authors.lastname: Nicklin
authors.forename: David A
authors.initials: DA
authors.lastname: Sandham
authors.forename: Katharine L
authors.initials: KL
authors.lastname: Turner
authors.forename: Morris F
authors.initials: MF
authors.lastname: Tweed
authors.forename: Simon J
authors.initials: SJ
authors.lastname: Watson
authors.forename: Mauro
authors.initials: M
authors.lastname: Zurini
mesh_terms: D015106:3',5'-Cyclic-GMP Phosphodiesterases / Q000037:antagonists & inhibitors*; D000818:Animals; D001682:Biological Availability; D002417:Cattle; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5; D004285:Dogs; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D007172:Erectile Dysfunction / Q000188:drug therapy; D006801:Humans; D020128:Inhibitory Concentration 50; D008297:Male; D010599:Pharmacokinetics; D020033:Protein Isoforms / Q000187:drug effects; D013329:Structure-Activity Relationship; D014970:Xanthines / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D004791:Enzyme Inhibitors; D020033:Protein Isoforms; D014970:Xanthines; D015106:3',5'-Cyclic-GMP Phosphodiesterases; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5; C517381:PDE5A protein, human