Discovery and Structure−Activity Relationship of Quinuclidine Benzamides as Agonists of α7 Nicotinic Acetylcholine ReceptorsClick to copy article linkArticle link copied!
- Alice L. Bodnar
- 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
Abstract

A library of benzamides was tested for α7 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 α7 nAChR agonist activity. The SAR diverged from the activity of this compound class verses the 5-HT3 receptor, a structural homologue of the α7 nAChR. PNU-282987, the most potent compound from this series, was also shown to open native α7 nAChRs in cultured rat neurons and to reverse an amphetamine-induced gating deficit in rats.
*
To whom correspondence should be addressed. Phone: 317-651-3855. Fax: 317-433-1685. E-mail: [email protected].
†
Current address: Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN 46285.
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