A pyridazine series of α2/α3 subtype selective GABAA agonists for the treatment of anxiety

RT Lewis, WP Blackaby, T Blackburn…

Index: Lewis, Richard T.; Blackaby, Wesley P.; Blackburn, Timothy; Jennings, Andrew S. R.; Pike, Andrew; Wilson, Rowan A.; Hallett, David J.; Cook, Susan M.; Ferris, Pushpinder; Marshall, George R.; Reynolds, David S.; Sheppard, Wayne F. A.; Smith, Alison J.; Sohal, Bindi; Stanley, Joanna; Tye, Spencer J.; Wafford, Keith A.; Atack, John R. Journal of Medicinal Chemistry, 2006 , vol. 49, # 8 p. 2600 - 2610

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Citation Number: 22

Abstract

The development of a series of GABAA α2/α3 subtype selective pyridazine based benzodiazepine site agonists as anxiolytic agents with reduced sedative/ataxic potential is described, including the discovery of 16, a remarkably α3-selective compound ideal for in vivo study. These ligands are antagonists at the α1 subtype, with good CNS penetration and receptor occupancy, and excellent oral bioavailability.