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1. 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

Author

G. Wishka, Donn, P. Walker, Daniel, M. Yates, Karen, C. Reitz, Steven, Jia, Shaojuan, K. Myers, Jason, L. Olson, Kirk, Jon Jacobsen, E., L. Wolfe, Mark, E. Groppi, Vincent, J. Hanchar, Alexander, A. Thornburgh, Bruce, A. Cortes-Burgos, Luz, H. F. Wong, Erik, A. Staton, Brian, J. Raub, Thomas, R. Higdon, Nicole, M. Wall, Theron, S. Hurst, Raymond, R. Walters, Rodney, E. Hoffmann, William, Hajos, Mihaly, Franklin, Stanley, Carey, Galen, H. Gold, Lisa, K. Cook, Karen, B. Sands, Steven, X. Zhao, Sabrina, R. Soglia, John, S. Kalgutkar, Amit, P. Arneric, Stephen, and N. Rogers, Bruce

Abstract

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 α7 neuronal nicotinic acetylcholine receptor (α7 nAChR), has been identified as a potential treatment of cognitive deficits in schizophrenia. Compound 14 is a potent and selective α7 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.

Published
2006

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