Structure-activity relationships for a series of pyrazine carboxamide CB1 antagonists are reported.� The pharmaceutical properties of the series are improved through introduction of a hydroxyl-containing sidechain. �This structural modification improves the ADME properties of an orally inactive series such that food intake reduction is achieved in rat feeding models. �(S)-5,6-Bis(4-chlorophenyl)-N-(1-hydroxy-4-methylpentan-2-yl)pyrazine-2-carboxamide elicits a 46% reduction in food intake when administered at 10 mg/kg to ad libidum fed rats 4h post-dose.