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Characterization of Novel Selective H1-Antihistamines for Clinical Evaluation in the Treatment of Insomnia

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posted on 10.09.2009, 00:00 by Wilna J. Moree, Bin-Feng Li, Florence Jovic, Timothy Coon, Jinghua Yu, Raymond S. Gross, Fabio Tucci, Dragan Marinkovic, Said Zamani-Kord, Siobhan Malany, Margaret J. Bradbury, Lisa M. Hernandez, Zhihong O’Brien, Jianyun Wen, Hua Wang, Samuel R. J. Hoare, Robert E. Petroski, Aida Sacaan, Ajay Madan, Paul D. Crowe, Graham Beaton
Analogues of the known H1-antihistamine R-dimethindene were profiled as potential agents for the treatment of insomnia. Several highly selective compounds were efficacious in rodent sleep models. On the basis of overall profile, indene 1d and benzothiophene 2a had pharmacokinetic properties suitable for evaluation in night time dosing. Compound 2a did not show an in vivo cardiovascular effect from weak hERG channel inhibition.