Novel benzothiophene H1-antihistamines for the treatment of insomnia.

Autor: Moree WJ; Neurocrine Biosciences, 12780 El Camino Real, San Diego, CA 92130, USA. wilna.moree@gmail.com, Jovic F, Coon T, Yu J, Li BF, Tucci FC, Marinkovic D, Gross RS, Malany S, Bradbury MJ, Hernandez LM, O'Brien Z, Wen J, Wang H, Hoare SR, Petroski RE, Sacaan A, Madan A, Crowe PD, Beaton G
Jazyk: angličtina
Zdroj: Bioorganic & medicinal chemistry letters [Bioorg Med Chem Lett] 2010 Apr 01; Vol. 20 (7), pp. 2316-20. Date of Electronic Publication: 2010 Feb 02.
DOI: 10.1016/j.bmcl.2010.01.134
Abstrakt: SAR of lead benzothiophene H(1)-antihistamine 2 was explored to identify backup candidates with suitable pharmacokinetic profiles for an insomnia program. Several potent and selective H(1)-antihistamines with a range of projected half-lives in humans were identified. Compound 16d had a suitable human half-life as demonstrated in a human microdose study, but variability in pharmacokinetic profile, attributed to metabolic clearance, prevented further development of this compound. Compound 28b demonstrated lower predicted clearance in preclinical studies, and may represent a more suitable backup compound.
(2010 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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