Imidazo[1,2-a]pyrimidines as functionally selective and orally bioavailable GABA-α2/α3 binding site agonists for the treatment of anxiety disorders

A series of high-affinity GABA(A) agonists with good oral bioavailability in rat and dog and functional selectivity for or the GABA(A)alpha 2 and -alpha 3 subtypes is reported. The 7-trifluoroinethylimidazopyrimidine 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.