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.
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.
Acker
Brad A
BA
Neuroscience Research, Pfizer Global Research and Development, Eastern Point Road, Groton, CT 06340, USA.
Jacobsen
E Jon
EJ
Rogers
Bruce N
BN
Wishka
Donn G
DG
Reitz
Steven C
SC
Piotrowski
David W
DW
Myers
Jason K
JK
Wolfe
Mark L
ML
Groppi
Vincent E
VE
Thornburgh
Bruce A
BA
Tinholt
Paula M
PM
Walters
Rodney R
RR
Olson
Barbara A
BA
Fitzgerald
Laura
L
Staton
Brian A
BA
Raub
Thomas J
TJ
Krause
Michael
M
Li
Kai S
KS
Hoffmann
William E
WE
Hajos
Mihaly
M
Hurst
Raymond S
RS
Walker
Daniel P
DP
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
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