2. Academic Validation
  3. Discovery of 4-(5-methyloxazolo[4,5-b]pyridin-2-yl)-1,4-diazabicyclo[3.2.2]nonane (CP-810,123), a novel alpha 7 nicotinic acetylcholine receptor agonist for the treatment of cognitive disorders in schizophrenia: synthesis, SAR development, and in vivo efficacy in cognition models

Discovery of 4-(5-methyloxazolo[4,5-b]pyridin-2-yl)-1,4-diazabicyclo[3.2.2]nonane (CP-810,123), a novel alpha 7 nicotinic acetylcholine receptor agonist for the treatment of cognitive disorders in schizophrenia: synthesis, SAR development, and in vivo efficacy in cognition models

  • J Med Chem. 2010 Feb 11;53(3):1222-37. doi: 10.1021/jm9015075.
Christopher J O'Donnell 1,  Bruce N Rogers,  Brian S Bronk,  Dianne K Bryce,  Jotham W Coe,  Karen K Cook,  Allen J Duplantier,  Edelweiss Evrard,  Mihaly Hajós,  William E Hoffmann,  Raymond S Hurst,  Noha Maklad,  Robert J Mather,  Stafford McLean,  Frank M Nedza,  Brian T O'Neill,  Langu Peng,  Weimin Qian,  Melinda M Rottas,  Steven B Sands,  Anne W Schmidt,  Alka V Shrikhande,  Douglas K Spracklin,  Diane F Wong,  Andy Zhang,  Lei Zhang
Affiliations

Affiliation

  • 1 Pfizer Global Research and Development, Groton Laboratories, Eastern Point Road, Groton, Connecticut 06340, USA. christopher.j.odonnell@pfizer.com
PMID: 20043678 DOI: 10.1021/jm9015075
Abstract

A novel alpha 7 nAChR Agonist, 4-(5-methyloxazolo[4,5-b]pyridin-2-yl)-1,4-diazabicyclo[3.2.2]nonane (24, CP-810,123), has been identified as a potential treatment for cognitive deficits associated with psychiatric or neurological conditions including schizophrenia and Alzheimer's disease. Compound 24 is a potent and selective compound with excellent pharmaceutical properties. In rodent, the compound displays high oral bioavailability and excellent brain penetration affording high levels of receptor occupancy and in vivo efficacy in auditory sensory gating and novel object recognition. The structural diversity of this compound and its preclinical in vitro and in vivo package support the hypothesis that alpha 7 nAChR agonists may have potential as a pharmacotherapy for the treatment of cognitive deficits in schizophrenia.

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