title: The discovery of novel, potent and selective PDE5 inhibitors.
abstract: The design and synthesis of a novel scaffold for potent and selective PDE5 inhibitors are described. Compound 3a was more potent (PDE5 IC50=0.31 nM) and selective (>10,000-fold vs PDE1 and 160-fold selective vs PDE6) PDE5 inhibitor than sildenafil.
authors.affiliation: Department of Discovery Chemistry, Bristol-Myers Squibb Pharmaceutical Research Institute, PO Box 5400, Princeton, NJ 08543-5400, USA. yingzhi.bi@bms.com
authors.forename: Y
authors.initials: Y
authors.lastname: Bi
authors.forename: P
authors.initials: P
authors.lastname: Stoy
authors.forename: L
authors.initials: L
authors.lastname: Adam
authors.forename: B
authors.initials: B
authors.lastname: He
authors.forename: J
authors.initials: J
authors.lastname: Krupinski
authors.forename: D
authors.initials: D
authors.lastname: Normandin
authors.forename: R
authors.initials: R
authors.lastname: Pongrac
authors.forename: L
authors.initials: L
authors.lastname: Seliger
authors.forename: A
authors.initials: A
authors.lastname: Watson
authors.forename: J E
authors.initials: JE
authors.lastname: Macor
mesh_terms: D015106:3',5'-Cyclic-GMP Phosphodiesterases; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5; D054707:Cyclic Nucleotide Phosphodiesterases, Type 6; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D020128:Inhibitory Concentration 50; D010726:Phosphodiesterase Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D010727:Phosphoric Diester Hydrolases / Q000187:drug effects*; D010879:Piperazines / Q000494:pharmacology; D011687:Purines; D000068677:Sildenafil Citrate; D013329:Structure-Activity Relationship; D013450:Sulfones
chemical_list: D010726:Phosphodiesterase Inhibitors; D010879:Piperazines; D011687:Purines; D013450:Sulfones; D000068677:Sildenafil Citrate; D010727:Phosphoric Diester Hydrolases; D015106:3',5'-Cyclic-GMP Phosphodiesterases; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5; D054707:Cyclic Nucleotide Phosphodiesterases, Type 6