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

详细信息	查看全文 | 推荐本文 |

• 作者：Nadine C. Becknell ; ^{nadinebecknell@aol.com} ; Jacquelyn A. Lyons ; Lisa D. Aimone ; Zeqi Huang ; John A. Gruner ; Rita Raddatz ; Robert L. Hudkins
• 关键词：Histamine H3 ; H3R antagonists ; CEP-26401 ; Pyridazinone
• 刊名：Bioorganic and Medicinal Chemistry
• 出版年：2012
• 期刊代码：9_09680896
• 类别：ch
• 出版时间：15 June, 2012
• 卷：20
• 期：12
• 页码：3880-3886
• 文件大小：1102 K

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.