Bioorganic & Medicinal Chemistry Letters 2004-04-05

Tricyclic pyridones as functionally selective human GABAA alpha 2/3 receptor-ion channel ligands.

James Crawforth, John R Atack, Susan M Cook, Karl R Gibson, Alan Nadin, Andrew P Owens, Andrew Pike, Michael Rowley, Alison J Smith, Bindi Sohal, Francine Sternfeld, Keith Wafford, Leslie J Street

Index: Bioorg. Med. Chem. Lett. 14(7) , 1679-82, (2004)

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Abstract

A series of tricyclic pyridones has been evaluated as benzodiazepine site ligands with functional selectivity for the alpha(3) over the alpha(1) containing subtype of the human GABA(A) receptor ion channel. This investigation led to the identification of a high affinity, functionally selective, orally bioavailable benzodiazepine site ligand that demonstrated activity in rodent anxiolysis models and reduced sedation relative to diazepam.