Referenced in: none

Automatically associated channels: Kv11.1

Title: Brain-penetrating 2-aminobenzimidazole H(1)-antihistamines for the treatment of insomnia.

Authors: Timothy Coon, Wilna J Moree, Binfeng Li, Jinghua Yu, Said Zamani-Kord, Siobhan Malany, Mark A Santos, Lisa M Hernandez, Robert E Petroski, Aixia Sun, Jenny Wen, Sue Sullivan, Jason Haelewyn, Michael Hedrick, Samuel J Hoare, Margaret J Bradbury, Paul D Crowe, Graham Beaton

Journal, date & volume: Bioorg. Med. Chem. Lett., 2009 Aug 1 , 19, 4380-4

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/19553115

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.