This communication reports SARs for the first orexin-1 receptor antagonist series of 1-aryl-3- quinolin-4-yl and 1-aryl-3-naphthyridin-4-yl ureas. One of these compounds, 31 (SB- 334867), has excellent selectivity for the orexin-1 receptor, blood–brain barrier permeability and shows in vivo activity following ip dosing.