Brain-penetrating 2-aminobenzimidazole H(1)-antihistamines for the treatment of insomnia.
Basic Information
ID: ALA1154013
Journal: Bioorg Med Chem Lett
Title: Brain-penetrating 2-aminobenzimidazole H(1)-antihistamines for the treatment of insomnia.
Authors: Coon T, Moree WJ, Li B, Yu J, Zamani-Kord S, Malany S, Santos MA, Hernandez LM, Petroski RE, Sun A, Wen J, Sullivan S, Haelewyn J, Hedrick M, Hoare SJ, Bradbury MJ, Crowe PD, Beaton G.
Abstract: The benzimidazole core of the selective non-brain-penetrating H(1)-antihistamine mizolastine was used to identify a series of brain-penetrating H(1)-antihistamines for the potential treatment of insomnia. Using cassette PK studies, brain-penetrating H(1)-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 discovery of 4i with a promising in vitro profile.
CiteXplore: 19553115
DOI: 10.1016/j.bmcl.2009.05.086
Patent ID: ┄