The discovery and structure-activity relationships of 2-(piperidin-3-yl)-1H-benzimidazoles as selective, CNS penetrating H1-antihistamines for insomnia.
| Autor: | Lavrador-Erb K; Neurocrine Biosciences, 12780 El Camino Real, San Diego, CA 92130, USA., Ravula SB, Yu J, Zamani-Kord S, Moree WJ, Petroski RE, Wen J, Malany S, Hoare SR, Madan A, Crowe PD, Beaton G |
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| Jazyk: | angličtina |
| Zdroj: | Bioorganic & medicinal chemistry letters [Bioorg Med Chem Lett] 2010 May 01; Vol. 20 (9), pp. 2916-9. Date of Electronic Publication: 2010 Mar 10. |
| DOI: | 10.1016/j.bmcl.2010.03.027 |
| Abstrakt: | 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. (2010 Elsevier Ltd. All rights reserved.) |
| Databáze: | MEDLINE |
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