Discovery of Imidazo[1,2-<i>b</i>][1,2,4]triazines as GABA_A α2/3 Subtype Selective Agonists for the Treatment of Anxiety

Abstract

The identification of a series of imidazo[1,2-b][1,2,4]triazines with high affinity and functional selectivity for the GABA(A) alpha3-containing receptor subtype is described, leading to the identification of a clinical candidate, 11. Compound 11 shows good bioavailability and half-life in preclinical species, and it is a nonsedating anxiolytic in both rat and squirrel monkey behavioral models.