Referenced in: none

Automatically associated channels: Kv11.1

Title: The discovery and structure-activity relationships of 2-(piperidin-3-yl)-1H-benzimidazoles as selective, CNS penetrating H1-antihistamines for insomnia.

Authors: Karine Lavrador-Erb, Satheesh Babu Ravula, Jinghua Yu, Said Zamani-Kord, Wilna J Moree, Robert E Petroski, Jianyun Wen, Siobhan Malany, Samuel R J Hoare, Ajay Madan, Paul D Crowe, Graham Beaton

Journal, date & volume: Bioorg. Med. Chem. Lett., 2010 May 1 , 20, 2916-9

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/20347297

Abstract
A series of 2-(3-aminopiperidine)-benzimidazoles were identified as selective H(1)-antihistamines for evaluation as potential sedative hypnotics. Representative compounds showed improved hERG selectivity over a previously identified 2-aminobenzimidazole series. While hERG activity could be modulated via manipulation of the benzimidazole N1 substituent, this approach led to a reduction in CNS exposure for the more selective compounds. One example, 9q, retained a suitable selectivity profile with CNS exposure equivalent to known centrally active H(1)-antihistamines.