title: Investigation of aminopyridiopyrazinones as PDE5 inhibitors: Evaluation of modifications to the central ring system.
abstract: Efforts to improve the potency and physical properties of the aminopyridiopyrazinone class of PDE5 inhibitors through modification of the core ring system are described. Five new ring systems are evaluated and features that impart improved potency and improved solubility are delineated.
authors.affiliation: Pfizer Global Research and Development, Chesterfield Parkway West, St. Louis, MO 63017, USA. robert.o.hughes@pfizer.com
authors.forename: Robert O
authors.initials: RO
authors.lastname: Hughes
authors.forename: John K
authors.initials: JK
authors.lastname: Walker
authors.forename: Jerry W
authors.initials: JW
authors.lastname: Cubbage
authors.forename: Yvette M
authors.initials: YM
authors.lastname: Fobian
authors.forename: D Joseph
authors.initials: DJ
authors.lastname: Rogier
authors.forename: Steve E
authors.initials: SE
authors.lastname: Heasley
authors.forename: Rhadika M
authors.initials: RM
authors.lastname: Blevis-Bal
authors.forename: Alan G
authors.initials: AG
authors.lastname: Benson
authors.forename: Dafydd R
authors.initials: DR
authors.lastname: Owen
authors.forename: E Jon
authors.initials: EJ
authors.lastname: Jacobsen
authors.forename: John N
authors.initials: JN
authors.lastname: Freskos
authors.forename: John M
authors.initials: JM
authors.lastname: Molyneaux
authors.forename: David L
authors.initials: DL
authors.lastname: Brown
authors.forename: William C
authors.initials: WC
authors.lastname: Stallings
authors.forename: Brad A
authors.initials: BA
authors.lastname: Acker
authors.forename: Todd M
authors.initials: TM
authors.lastname: Maddux
authors.forename: Mike B
authors.initials: MB
authors.lastname: Tollefson
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Williams
authors.forename: Joseph B
authors.initials: JB
authors.lastname: Moon
authors.forename: Brent V
authors.initials: BV
authors.lastname: Mischke
authors.forename: Jeanne M
authors.initials: JM
authors.lastname: Rumsey
authors.forename: Yi
authors.initials: Y
authors.lastname: Zheng
authors.forename: Alan
authors.initials: A
authors.lastname: Macinnes
authors.forename: Brian R
authors.initials: BR
authors.lastname: Bond
authors.forename: Ying
authors.initials: Y
authors.lastname: Yu
mesh_terms: D000284:Administration, Oral; D000631:Aminopyridines / Q000138:chemical synthesis* / Q000494:pharmacology; D000818:Animals; D002626:Chemistry, Pharmaceutical / Q000379:methods; D006152:Cyclic GMP / Q000737:chemistry; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5 / Q000737:chemistry; D015195:Drug Design; D006801:Humans; D006863:Hydrogen-Ion Concentration; D006973:Hypertension / Q000188:drug therapy; D008861:Microsomes / Q000187:drug effects; D008956:Models, Chemical; D058986:Phosphodiesterase 5 Inhibitors; D010726:Phosphodiesterase Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D011719:Pyrazines / Q000138:chemical synthesis* / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012995:Solubility
chemical_list: D000631:Aminopyridines; D058986:Phosphodiesterase 5 Inhibitors; D010726:Phosphodiesterase Inhibitors; D011719:Pyrazines; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5; D006152:Cyclic GMP