Brain-penetrating 2-aminobenzimidazole H 1-antihistamines for the treatment of insomnia

…, WJ Moree, B Li, J Yu, S Zamani-Kord, S Malany…

文献索引：Coon, Timothy; Moree, Wilna J.; Li, Binfeng; Yu, Jinghua; Zamani-Kord, Said; Malany, Siobhan; Santos, Mark A.; Hernandez, Lisa M.; Petroski, Robert E.; Sun, Aixia; Wen, Jenny; Sullivan, Sue; Haelewyn, Jason; Hedrick, Michael; Hoare, Samuel J.; Bradbury, Margaret J.; Crowe, Paul D.; Beaton, Graham Bioorganic and Medicinal Chemistry Letters, 2009 , vol. 19, # 15 p. 4380 - 4384

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被引用次数: 21

摘要

The benzimidazole core of the selective non-brain-penetrating H1-antihistamine mizolastine was used to identify a series of brain-penetrating H1-antihistamines for the potential treatment of insomnia. Using cassette PK studies, brain-penetrating H1-antihistamines were identified and in vivo efficacy was demonstrated in a rat EEG/EMG model. Further optimization focused on strategies to attenuate an identified hERG liability, leading to the ...