title: Identification of a brain penetrant PDE9A inhibitor utilizing prospective design and chemical enablement as a rapid lead optimization strategy.
abstract: By use of chemical enablement and prospective design, a novel series of selective, brain penetrant PDE9A inhibitors have been identified that are capable of producing in vivo elevations of brain cGMP.
authors.affiliation: Neuroscience Chemistry, Pfizer Global Research and Development, Groton, CT 06340, USA.
authors.forename: Patrick R
authors.initials: PR
authors.lastname: Verhoest
authors.forename: Caroline
authors.initials: C
authors.lastname: Proulx-Lafrance
authors.forename: Michael
authors.initials: M
authors.lastname: Corman
authors.forename: Lois
authors.initials: L
authors.lastname: Chenard
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Helal
authors.forename: Xinjun
authors.initials: X
authors.lastname: Hou
authors.forename: Robin
authors.initials: R
authors.lastname: Kleiman
authors.forename: Shenping
authors.initials: S
authors.lastname: Liu
authors.forename: Eric
authors.initials: E
authors.lastname: Marr
authors.forename: Frank S
authors.initials: FS
authors.lastname: Menniti
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Schmidt
authors.forename: Michelle
authors.initials: M
authors.lastname: Vanase-Frawley
authors.forename: Anne W
authors.initials: AW
authors.lastname: Schmidt
authors.forename: Robert D
authors.initials: RD
authors.lastname: Williams
authors.forename: Frederick R
authors.initials: FR
authors.lastname: Nelson
authors.forename: Kari R
authors.initials: KR
authors.lastname: Fonseca
authors.forename: Spiros
authors.initials: S
authors.lastname: Liras
mesh_terms: D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000201:enzymology* / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism; D006801:Humans; D006860:Hydrogen Bonding; D051379:Mice; D008958:Models, Molecular; D010726:Phosphodiesterase Inhibitors / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology
chemical_list: D010726:Phosphodiesterase Inhibitors; D015105:3',5'-Cyclic-AMP Phosphodiesterases; C116137:PDE9A protein, human; C507055:Pde9a protein, mouse; D006152:Cyclic GMP