title: Discovery of N-[(3R,5R)-1-azabicyclo[3.2.1]oct-3-yl]furo[2,3-c]pyridine-5-carboxamide as an agonist of the alpha7 nicotinic acetylcholine receptor: in vitro and in vivo activity.
abstract: A novel alpha7 nAChR agonist, N-[(3R,5R)-1-azabicyclo[3.2.1]oct-3-yl]furo[2,3-c]pyridine-5-carboxamide (3a, PHA-709829), has been identified for the potential treatment of cognitive deficits in schizophrenia. The compound shows potent and selective alpha7 in vitro activity, excellent brain penetration, good rat oral bioavailability and robust in vivo efficacy in a rat auditory sensory gating model.
authors.affiliation: Neuroscience Research, Pfizer Global Research and Development, Eastern Point Road, Groton, CT 06340, USA.
authors.forename: Brad A
authors.initials: BA
authors.lastname: Acker
authors.forename: E Jon
authors.initials: EJ
authors.lastname: Jacobsen
authors.forename: Bruce N
authors.initials: BN
authors.lastname: Rogers
authors.forename: Donn G
authors.initials: DG
authors.lastname: Wishka
authors.forename: Steven C
authors.initials: SC
authors.lastname: Reitz
authors.forename: David W
authors.initials: DW
authors.lastname: Piotrowski
authors.forename: Jason K
authors.initials: JK
authors.lastname: Myers
authors.forename: Mark L
authors.initials: ML
authors.lastname: Wolfe
authors.forename: Vincent E
authors.initials: VE
authors.lastname: Groppi
authors.forename: Bruce A
authors.initials: BA
authors.lastname: Thornburgh
authors.forename: Paula M
authors.initials: PM
authors.lastname: Tinholt
authors.forename: Rodney R
authors.initials: RR
authors.lastname: Walters
authors.forename: Barbara A
authors.initials: BA
authors.lastname: Olson
authors.forename: Laura
authors.initials: L
authors.lastname: Fitzgerald
authors.forename: Brian A
authors.initials: BA
authors.lastname: Staton
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Raub
authors.forename: Michael
authors.initials: M
authors.lastname: Krause
authors.forename: Kai S
authors.initials: KS
authors.lastname: Li
authors.forename: William E
authors.initials: WE
authors.lastname: Hoffmann
authors.forename: Mihaly
authors.initials: M
authors.lastname: Hajos
authors.forename: Raymond S
authors.initials: RS
authors.lastname: Hurst
authors.forename: Daniel P
authors.initials: DP
authors.lastname: Walker
mesh_terms: D000818:Animals; D053961:Azabicyclo Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001549:Benzamides / Q000494:pharmacology; D001798:Blood Proteins / Q000187:drug effects; D001643:Bridged Bicyclo Compounds / Q000494:pharmacology; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D006801:Humans; D051379:Mice; D008862:Microsomes, Liver / Q000187:drug effects; D008968:Molecular Conformation; D018722:Nicotinic Agonists / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D011725:Pyridines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D011812:Quinuclidines / Q000494:pharmacology; D051381:Rats; D011976:Receptors, Muscarinic / Q000187:drug effects; D011978:Receptors, Nicotinic / Q000187:drug effects*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D064569:alpha7 Nicotinic Acetylcholine Receptor
chemical_list: D053961:Azabicyclo Compounds; D001549:Benzamides; D001798:Blood Proteins; D001643:Bridged Bicyclo Compounds; D019086:Bridged Bicyclo Compounds, Heterocyclic; C579167:Chrna7 protein, human; C579166:Chrna7 protein, mouse; C579165:Chrna7 protein, rat; C513163:N-(1-azabicyclo(2.2.2)oct-3-yl)furo(2,3-c)pyridine-5-carboxamide; C530874:N-(1-azabicyclo(3.2.1)oct-3-yl)furo(2,3-c)pyridine-5-carboxamide; D018722:Nicotinic Agonists; C498513:PNU-282987; D011725:Pyridines; D011812:Quinuclidines; D011976:Receptors, Muscarinic; D011978:Receptors, Nicotinic; D064569:alpha7 Nicotinic Acetylcholine Receptor