Here, we describe a novel OX2 receptor antagonist N-((1H-imidazol-2-yl)methyl)-N-([1,1′-biphenyl]-2-yl)-4-fluorobenzenesulfonamide hydrochloride (LSN2424100, Figure 1), and characterize it in terms of its in vitro binding affinity, functional selectivity, and pharmacokinetic properties, and further examine its effects on c-fos expression in the rat prefrontal cortex, a brain region implicated in the pathophysiology of depression (Drevets et al., 2008), in response to restraint stress. Here, FOS is linked to depressive disorder.