Novel morpholine ketone analogs as potent histamine H3 receptor inverse agonists with wake activity

Abstract Structure–activity relationship on a novel ketone class of H 3 R antagonists/inverse agonists is disclosed. Compound 4 showed excellent target potency, selectivity and brain penetration. Evaluation of antagonist 4 in the rat EEG/EMG model demonstrated robust wake activity thereby establishing preclinical proof of concept.