A Pyridazine Series of α2/α3 Subtype Selective GABAA Agonists for the Treatment of Anxiety

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.