Identification of pyridazin-3-one derivatives as potent, selective histamine H sub(3 receptor inverse agonists with robust wake activity)

H sub(3R structure-activity relationships on a novel class of pyridazin-3-one H) sub(3)R antagonists/inverse agonists are disclosed. Modifications of the pyridazinone core, central phenyl ring and linker led to the identification of molecules with excellent target potency, selectivity and pharmacokinetic properties. Compounds 13 and 21 displayed potent functional H sub(3R antagonism in vivo in the rat dipsogenia model and demonstrated robust wake activity in the rat EEG/EMG model.)