title: Design, synthesis and biological activity of beta-carboline-based type-5 phosphodiesterase inhibitors.
abstract: The SAR of a series of beta-carboline derived type 5 phosphodiesterase inhibitors has been explored and we have discovered compounds with excellent levels of PDE5 potency and selectivity over PDE6. However, the series exhibits low levels of selectivity over PDE11, a phosphodiesterase with unknown function.
authors.affiliation: Department of Discovery Chemistry, Pfizer Global Research and Development, Sandwich Laboratories (IPC351), Ramsgate Road, Sandwich, Kent, CT13 9NJ, UK. graham_maw@sandwich.pfizer.com
authors.forename: Graham N
authors.initials: GN
authors.lastname: Maw
authors.forename: Charlotte M N
authors.initials: CM
authors.lastname: Allerton
authors.forename: Eugene
authors.initials: E
authors.lastname: Gbekor
authors.forename: William A
authors.initials: WA
authors.lastname: Million
mesh_terms: D015106:3',5'-Cyclic-GMP Phosphodiesterases; D000818:Animals; D001555:Benzene Derivatives / Q000737:chemistry / Q000494:pharmacology; D002243:Carbolines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002417:Cattle; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5; D004285:Dogs; D015195:Drug Design; D006801:Humans; D020128:Inhibitory Concentration 50; D007527:Isoenzymes; D010726:Phosphodiesterase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism*; D011759:Pyrrolidines / Q000737:chemistry / Q000494:pharmacology; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors; D018411:Spodoptera; D013329:Structure-Activity Relationship
chemical_list: D001555:Benzene Derivatives; D002243:Carbolines; D007527:Isoenzymes; D010726:Phosphodiesterase Inhibitors; D011759:Pyrrolidines; D011994:Recombinant Proteins; D010727:Phosphoric Diester Hydrolases; D015106:3',5'-Cyclic-GMP Phosphodiesterases; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5; C517381:PDE5A protein, human