Selective, Orally Active γ-Aminobutyric Acid A α5 Receptor Inverse Agonists as Cognition Enhancers
Journal of Medicinal Chemistry2004Vol. 47(9), pp. 2176–2179
Citations Over TimeTop 10% of 2004 papers
Francine Sternfeld, Robert W. Carling, Richard A. Jelley, Tamara Ladduwahetty, Kevin J. Merchant, Kevin W. Moore, Austin J. Reeve, Leslie J. Street, Desmond O’Connor, Bindi Sohal, John Atack, Susan M. Cook, Guy R. Seabrook, Keith A. Wafford, F.D. Tattersall, Neil Collinson, Gerard R. Dawson, José L. Castro, Angus M. MacLeod
Abstract
Nonselective inverse agonists at the gamma-aminobutyric acid(A) (GABA-A) benzodiazepine binding site have cognition-enhancing effects in animals but are anxiogenic and can precipitate convulsions. Herein, we describe novel GABA-A alpha5 subtype inverse agonists leading to the identification of 16 as an orally active, functionally selective compound that enhances cognition in animals without anxiogenic or convulsant effects. Compounds of this type may be useful in the symptomatic treatment of memory impairment associated with Alzheimer's disease and related dementias.
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