A series of 5-arylamino-1,2,4-triazin-6(1H)-ones was synthesized and evaluated as antagonists at the corticotropin releasing factor receptor. Formation of CYP-mediated oxidative reactive metabolites previously observed in a related N-3-phenylpyrazinone structure was minimized by incorporation of the additional ring nitrogen found in the triazinones. (C) 2010 Elsevier Ltd. All rights reserved.