Imidazo[1,2-a]pyrimidines as Functionally Selective and Orally Bioavailable GABAAα2/α3 Binding Site Agonists for the Treatment of Anxiety Disorders

Abstract
A series of high-affinity GABAA agonists with good oral bioavailability in rat and dog and functional selectivity for the GABAAα2 and -α3 subtypes is reported. The 7-trifluoromethylimidazopyrimidine 14g and the 7-propan-2-olimidazopyrimidine 14k are anxiolytic in both conditioned and unconditioned animal models of anxiety with minimal sedation observed at full BZ binding site occupancy.