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.

Bioorganic & medicinal chemistry letters 2008 May 1; In press

Acker B BA, Jacobsen E EJ, Rogers B BN, Wishka D DG, Reitz S SC, Piotrowski D DW, Myers J JK, Wolfe M ML, Groppi V VE, Thornburgh B BA, Tinholt P PM, Walters R RR, Olson B BA, Fitzgerald L, Staton B BA, Raub T TJ, Krause M, Li K KS, Hoffmann W WE, Hajos M, Hurst R RS, Walker D DP

Neuroscience Research, Pfizer Global Research and Development, Eastern Point Road, Groton, CT 06340, USA.

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.

Keywords: alpha7 nicotinic schizophrenia PHA-709829