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

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

  • Bioorg Med Chem Lett. 2010 May 1;20(9):2916-9. doi: 10.1016/j.bmcl.2010.03.027.
Karine Lavrador-Erb 1,  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
Affiliations

Affiliation

  • 1 Neurocrine Biosciences, 12780 El Camino Real, San Diego, CA 92130, USA.
PMID: 20347297 DOI: 10.1016/j.bmcl.2010.03.027
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.

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