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

  • Bioorg Med Chem Lett. 2008 Jun 15;18(12):3611-5. doi: 10.1016/j.bmcl.2008.04.070.
Brad A Acker  1 ,  E Jon Jacobsen ,  Bruce N Rogers ,  Donn G Wishka ,  Steven C Reitz ,  David W Piotrowski ,  Jason K Myers ,  Mark L Wolfe ,  Vincent E Groppi ,  Bruce A Thornburgh ,  Paula M Tinholt ,  Rodney R Walters ,  Barbara A Olson ,  Laura Fitzgerald ,  Brian A Staton ,  Thomas J Raub ,  Michael Krause ,  Kai S Li ,  William E Hoffmann ,  Mihaly Hajos ,  Raymond S Hurst ,  Daniel P Walker
Affiliations
  • 1. Neuroscience Research, Pfizer Global Research and Development, Eastern Point Road, Groton, CT 06340, USA.
PMID: 18490160 DOI: 10.1016/j.bmcl.2008.04.070
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.