7-(1,1-Dimethylethyl)-6-(2-ethyl-2 H -1,2,4- triazol-3-ylmethoxy)-3-(2-fluorophenyl)- 1,2,4-triazolo[4,3- b ]pyridazine: A Functionally Selective γ-Aminobutyric Acid A (GABA A ) α2/α3-Subtype Selective Agonist That Exhibits Potent Anxiolytic Activity but Is Not Sedating in Animal Models

There is increasing evidence that compounds with selectivity for gamma-aminobutyric acid(A) (GABA(A)) alpha2- and/or alpha3-subtypes may retain the desirable anxiolytic activity of nonselective benzodiazepines but possess an improved side effect profile. Herein we describe a novel series of GABA(A) alpha2/alpha3 subtype-selective agonists leading to the identification of the development candidate 17, a nonsedating anxiolytic in preclinical animal assays.