| Autor: |
Juan A, González-Vera, Rocío A, Medina, Mar, Martín-Fontecha, Angel, Gonzalez, Tania, de la Fuente, Henar, Vázquez-Villa, Javier, García-Cárceles, Joaquín, Botta, Peter J, McCormick, Bellinda, Benhamú, Leonardo, Pardo, María L, López-Rodríguez |
| Rok vydání: |
2016 |
| Předmět: |
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| Zdroj: |
Scientific Reports |
| ISSN: |
2045-2322 |
| Popis: |
Serotonin 5-HT6 receptor has been proposed as a promising therapeutic target for cognition enhancement though the development of new antagonists is still needed to validate these molecules as a drug class for the treatment of Alzheimer’s disease and other pathologies associated with memory deficiency. As part of our efforts to target the 5-HT6 receptor, new benzimidazole-based compounds have been designed and synthesized. Site-directed mutagenesis and homology models show the importance of a halogen bond interaction between a chlorine atom of the new class of 5-HT6 receptor antagonists identified herein and a backbone carbonyl group in transmembrane domain 4. In vitro pharmacological characterization of 5-HT6 receptor antagonist 7 indicates high affinity and selectivity over a panel of receptors including 5-HT2B subtype and hERG channel, which suggests no major cardiac issues. Compound 7 exhibited in vivo procognitive activity (1 mg/kg, ip) in the novel object recognition task as a model of memory deficit. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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