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

…, LD Aimone, Z Huang, JA Gruner, R Raddatz…

文献索引：Becknell, Nadine C.; Lyons, Jacquelyn A.; Aimone, Lisa D.; Huang, Zeqi; Gruner, John A.; Raddatz, Rita; Hudkins, Robert L. Bioorganic and Medicinal Chemistry, 2012 , vol. 20, # 12 p. 3880 - 3886

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被引用次数: 8

摘要

A novel series of 4-pyridazin-3-one and 5-pyridazin-3-one analogues were designed and synthesized as H3R antagonists. Structure–activity relationship revealed the 5-pyridazin-3- ones 8a and S-methyl 8b had excellent human and rat H3R 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.