Discovery of N-[(3R)-1-Azabicyclo[2.2.2]oct-3-yl]furo[2,3-c]pyridine-5-carboxamide, an Agonist of the α7 Nicotinic Acetylcholine Receptor, for the Potential Treatment of Cognitive Deficits in Schizophrenia: Synthesis and Structure−Activity Relationship

Autor: Arneric Sp, Karen K. Cook, Thomas J. Raub, Bruce N. Rogers, Mark L. Wolfe, Eric Jon Jacobsen, Vincent E. Groppi, Carey G, Brian A. Staton, Daniel P. Walker, Raymond S. Hurst, Luz A. Cortes-Burgos, Rodney R. Walters, Donn G. Wishka, Theron M. Wall, Jia S, Hanchar Aj, Karen M. Yates, Steven B. Sands, Bruce A. Thornburgh, Gold Lh, Soglia, Jason K. Myers, Franklin S, Steven Charles Reitz, Sabrina X. Zhao, Amit S. Kalgutkar, Nicole R. Higdon, Olson Kl, Erik H. F. Wong, Mihály Hajós, William E. Hoffmann
Rok vydání: 2006
Předmět:
Male
Agonist
Quinuclidines
medicine.medical_specialty
Psychosis
Patch-Clamp Techniques
alpha7 Nicotinic Acetylcholine Receptor
medicine.drug_class
Biological Availability
Carboxamide
In Vitro Techniques
Receptors
Nicotinic
Pharmacology
Rats
Sprague-Dawley
Radioligand Assay
Structure-Activity Relationship
Drug Stability
Memory
In vivo
Internal medicine
Drug Discovery
medicine
Animals
Humans
Learning
Structure–activity relationship
Nicotinic Agonists
Nootropic Agents
Acetylcholine receptor
Neurons
Chemistry
Brain
Recognition
Psychology
Stereoisomerism
Bridged Bicyclo Compounds
Heterocyclic
medicine.disease
Ether-A-Go-Go Potassium Channels
Rats
Nicotinic acetylcholine receptor
Endocrinology
Nicotinic agonist
Evoked Potentials
Auditory
Microsomes
Liver
Schizophrenia
Molecular Medicine
Cognition Disorders
Zdroj: Journal of Medicinal Chemistry. 49:4425-4436
ISSN: 1520-4804
0022-2623
DOI: 10.1021/jm0602413
Popis: 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 alpha7 nAChR agonist with an excellent in vitro profile. The compound is characterized by rapid brain penetration and high oral bioavailability in rat and demonstrates in vivo efficacy in auditory sensory gating and, in an in vivo model to assess cognitive performance, novel object recognition.
Databáze: OpenAIRE
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