Discovery, synthesis, selectivity modulation and DMPK characterization of 5-azaspiro[2.4]heptanes as potent orexin receptor antagonists.
Bioorg Med Chem Lett
; 23(9): 2653-8, 2013 May 01.
Article
em En
| MEDLINE
| ID: mdl-23535328
ABSTRACT
Starting from a orexin 1 receptor selective antagonist 4,4-disubstituted piperidine series a novel potent 5-azaspiro[2.4]heptane dual orexin 1 and orexin 2 receptor antagonist class has been discovered. SAR and Pharmacokinetic optimization of this series is herein disclosed. Lead compound 15 exhibits potent activity against orexin 1 and orexin 2 receptors along with low cytochrome P450 inhibition potential, good brain penetration and oral bioavailability in rats.
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1
Coleções:
01-internacional
Base de dados:
MEDLINE
Limite:
Animals
Idioma:
En
Ano de publicação:
2013
Tipo de documento:
Article