Identification of a novel selective H1-antihistamine with optimized pharmacokinetic properties for clinical evaluation in the treatment of insomnia.

Autor: Moree WJ; Neurocrine Biosciences, 12780 El Camino Real, San Diego, CA 92130, USA. wilna.moree@gmail.com, Li BF, Zamani-Kord S, Yu J, Coon T, Huang C, Marinkovic D, Tucci FC, Malany S, Bradbury MJ, Hernandez LM, Wen J, Wang H, Hoare SR, Petroski RE, Jalali K, Yang C, Sacaan A, Madan A, Crowe PD, Beaton G
Jazyk: angličtina
Zdroj: Bioorganic & medicinal chemistry letters [Bioorg Med Chem Lett] 2010 Oct 01; Vol. 20 (19), pp. 5874-8. Date of Electronic Publication: 2010 Aug 03.
DOI: 10.1016/j.bmcl.2010.07.117
Abstrakt: Analogs of the known H(1)-antihistamine R-dimethindene with suitable selectivity for key GPCRs, P450 enzymes and hERG channel were assessed for metabolism profile and in vivo properties. Several analogs were determined to exhibit diverse metabolism. One of these compounds, 10a, showed equivalent efficacy in a rat EEG/EMG model to a previously identified clinical candidate and a potentially superior pharmacokinetic profile as determined from a human microdose study.
(Copyright © 2010 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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