Discovery and structure-activity relationship of quinuclidine benzamides as agonists of alpha7 nicotinic acetylcholine receptors

  • J Med Chem. 2005 Feb 24;48(4):905-8. doi: 10.1021/jm049363q.
Alice L Bodnar  1 ,  Luz A Cortes-Burgos ,  Karen K Cook ,  Dac M Dinh ,  Vincent E Groppi ,  Mihaly Hajos ,  Nicole R Higdon ,  William E Hoffmann ,  Raymond S Hurst ,  Jason K Myers ,  Bruce N Rogers ,  Theron M Wall ,  Mark L Wolfe ,  Erik Wong
Affiliations
  • 1. Department of Neuroscience, Global Research and Development, Pfizer Inc., Groton, CT, USA.
PMID: 15715459 DOI: 10.1021/jm049363q
Abstract

A library of benzamides was tested for alpha7 nicotinic acetylcholine receptor (nAChR) agonist activity using a chimeric receptor in a functional, cell-based, high-throughput assay. From this library, quinuclidine benzamides were found to have alpha7 nAChR agonist activity. The SAR diverged from the activity of this compound class verses the 5-HT(3) receptor, a structural homologue of the alpha7 nAChR. PNU-282987, the most potent compound from this series, was also shown to open native alpha7 nAChRs in cultured rat neurons and to reverse an amphetamine-induced gating deficit in rats.

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