合成和评价 4-和 5-哒嗪-3-酮苯氧丙胺类似物作为组胺-3 受体拮抗剂。
Synthesis and evaluation of 4- and 5-pyridazin-3-one phenoxypropylamine analogues as histamine-3 receptor antagonists.
机构信息
Discovery Research, Cephalon, Inc., 145 Brandywine Parkway, West Chester, PA 19380, USA.
出版信息
Bioorg Med Chem. 2012 Jun 15;20(12):3880-6. doi: 10.1016/j.bmc.2012.04.028. Epub 2012 Apr 20.
A novel series of 4-pyridazin-3-one and 5-pyridazin-3-one analogues were designed and synthesized as H(3)R antagonists. Structure-activity relationship revealed the 5-pyridazin-3-ones 8a and S-methyl 8b had excellent human and rat H(3)R 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.
设计并合成了一系列新型的 4-哒嗪-3-酮和 5-哒嗪-3-酮类似物作为 H(3)R 拮抗剂。构效关系研究表明，5-哒嗪-3-酮 8a 和 S-甲基 8b 对人和大鼠 H(3)R 具有优异的亲和力和可接受的药代动力学性质。体内活性评价表明，8a 在大鼠致渴模型中具有很强的活性，在大鼠 EEG/EMG 模型中具有很强的促醒活性。
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