Discovery of N-[(3R)-1-azabicyclo[2.2.2]oct-3-yl]furo[2,3-c]pyridine-5-carboxamide, an agonist of the alpha7 nicotinic acetylcholine receptor, for the potential treatment of cognitive deficits in schizophrenia: synthesis and structure--activity relationship

N-[(3R)-1-Azabicyclo[2.2.2]oct-3-yl]furo[2,3-c]pyridine-5-carboxamide (14, PHA-543,613), a novel agonist of the alpha7 neuronal nicotinic acetylcholine receptor (alpha7 nAChR), has been identified as a potential treatment of cognitive deficits in schizophrenia. Compound 14 is a potent and selective...

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Veröffentlicht in:	Journal of medicinal chemistry 2006-07, Vol.49 (14), p.4425-4436
Hauptverfasser:	Wishka, Donn G, Walker, Daniel P, Yates, Karen M, Reitz, Steven C, Jia, Shaojuan, Myers, Jason K, Olson, Kirk L, Jacobsen, E Jon, Wolfe, Mark L, Groppi, Vincent E, Hanchar, Alexander J, Thornburgh, Bruce A, Cortes-Burgos, Luz A, Wong, Erik H F, Staton, Brian A, Raub, Thomas J, Higdon, Nicole R, Wall, Theron M, Hurst, Raymond S, Walters, Rodney R, Hoffmann, William E, Hajos, Mihaly, Franklin, Stanley, Carey, Galen, Gold, Lisa H, Cook, Karen K, Sands, Steven B, Zhao, Sabrina X, Soglia, John R, Kalgutkar, Amit S, Arneric, Stephen P, Rogers, Bruce N
Format:	Artikel
Sprache:	eng
Schlagworte:	alpha7 Nicotinic Acetylcholine Receptor Animals Biological Availability Brain - metabolism Bridged Bicyclo Compounds, Heterocyclic - chemical synthesis Bridged Bicyclo Compounds, Heterocyclic - chemistry Bridged Bicyclo Compounds, Heterocyclic - pharmacology Cognition Disorders - drug therapy Drug Stability Ether-A-Go-Go Potassium Channels - drug effects Evoked Potentials, Auditory - drug effects Humans In Vitro Techniques Learning - drug effects Male Memory - drug effects Microsomes, Liver - drug effects Microsomes, Liver - metabolism Neurons - drug effects Neurons - physiology Nicotinic Agonists - chemical synthesis Nicotinic Agonists - pharmacokinetics Nicotinic Agonists - pharmacology Nootropic Agents - chemical synthesis Nootropic Agents - pharmacokinetics Nootropic Agents - pharmacology Patch-Clamp Techniques Quinuclidines - chemical synthesis Quinuclidines - chemistry Quinuclidines - pharmacology Radioligand Assay Rats Rats, Sprague-Dawley Receptors, Nicotinic - metabolism Receptors, Nicotinic - physiology Recognition (Psychology) - drug effects Schizophrenia - drug therapy Stereoisomerism Structure-Activity Relationship
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