| Literature DB >> 21498079 |
Cristobal Alhambra1, Chris Becker, Timothy Blake, Amy Hui-Fang Chang, James R Damewood, Thalia Daniels, Bruce T Dembofsky, David A Gurley, James E Hall, Keith J Herzog, Carey L Horchler, Cyrus J Ohnmacht, Richard Jon Schmiesing, Adam Dudley, Maria D Ribadeneira, Katherine S Knappenberger, Carla Maciag, Mark M Stein, Maninder Chopra, Xiaodong F Liu, Edward P Christian, Jeffrey L Arriza, Marc J Chapdelaine.
Abstract
Positive modulators at the benzodiazepine site of α2- and α3-containing GABA(A) receptors are believed to be anxiolytic. Through oocyte voltage clamp studies, we have discovered two series of compounds that are positive modulators at α2-/α3-containing GABA(A) receptors and that show no functional activity at α1-containing GABA(A) receptors. We report studies to improve this functional selectivity and ultimately deliver clinical candidates. The functional SAR of cinnolines and quinolines that are positive allosteric modulators of the α2- and α3-containing GABA(A) receptors, while simultaneously neutral antagonists at α1-containing GABA(A) receptors, is described. Such functionally selective modulators of GABA(A) receptors are expected to be useful in the treatment of anxiety and other psychiatric illnesses.Entities:
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Year: 2011 PMID： 21498079 DOI： 10.1016/j.bmc.2011.03.035
Source DB: PubMed Journal: Bioorg Med Chem ISSN： 0968-0896 Impact factor: 3.641