Synthesis and evaluation of 4- and 5-pyridazin-3-one phenoxypropylamine analogues as histamine-3 receptor antagonists

摘要

A novel series of 4-pyridazin-3-one and 5-pyridazin-3-one analogues were designed and synthesized as H 3R antagonists. Structure-activity relationship revealed the 5-pyridazin-3-ones 8a and S-methyl 8b had excellent human and rat H 3R affinities, and acceptable pharmacokinetic properties. In vivo evaluation of 8a showed potent activity in the rat dipsogenia model and robust wake-promoting activity in the rat EEG/EMG model.