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

Aryl Piperazinyl Ureas as Inhibitors of Fatty Acid Amide Hydrolase (FAAH) in Rat, Dog, and Primate

A series of aryl piperazinyl ureas that act as covalent inhibitors of fatty acid amide hydrolase (FAAH) is described. A potent and selective (does not inhibit FAAH-2) member of this class, JNJ-40355003, was found to elevate the plasma levels of three fatty acid amides: anandamide, oleoyl ethanolamide, and palmitoyl ethanolamide, in the rat, dog, and cynomolgous monkey. The elevation of the levels of these lipids in the plasma of monkeys suggests that FAAH-2 may not play a significant role in regulating plasma levels of fatty acid ethanolamides in primates