| Autor: |
Sams AG; Medicinal Chemistry Research, Lundbeck Research Denmark, H. Lundbeck A/S, Ottiliavej 9, DK-2500 Valby, Denmark. anette.sams@leo-pharma.com, Hentzer M, Mikkelsen GK, Larsen K, Bundgaard C, Plath N, Christoffersen CT, Bang-Andersen B |
| Jazyk: |
angličtina |
| Zdroj: |
Journal of medicinal chemistry [J Med Chem] 2010 Sep 09; Vol. 53 (17), pp. 6386-97. |
| DOI: |
10.1021/jm100697g |
| Abstrakt: |
The discovery and structure-activity relationship (SAR) of a series of allosteric muscarinic M(1) receptor agonists are described. Compound 17 (Lu AE51090) was identified as a representative compound from the series, based on its high selectivity as an agonist at the muscarinic M(1) receptor across a panel of muscarinic receptor subtypes. Furthermore, 17 displayed a high degree of selectivity when tested in a broad panel of G-protein-coupled receptors, ion channels, transporters, and enzymes, and 17 showed an acceptable pharmacokinetic profile and sufficient brain exposure in rodents in order to characterize the compound in vivo. Hence, in a rodent model of learning and memory, 17 reversed delay-induced natural forgetting, suggesting a procognitive potential of 17. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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