Identification and SAR of Glycine Benzamides as Potent Agonists for the GPR139 Receptor

A focused high throughput screening for GPR139 was completed for a select 100K compounds, and new agonist leads were identified. Subsequent analysis and structure–activity relationship studies identified (<i>S</i>)-3-chloro-<i>N</i>-(2-oxo-2-((1-phenylethyl)­amino)­ethyl)­benzamide <b>7c</b> as a potent and selective agonist of hGPR139 with an EC₅₀ = 16 nM. The compound was found to cross the blood–brain barrier and have good drug-like properties amenable for oral dosing in rat