Do GluN2B subunit containing NMDA receptors tolerate a fluorine atom in the phenylalkyl side chain?
| Autor: | Yoshihiro Shuto, Masato Kitamura, Dirk Schepmann, Simone Thum, Louisa Temme, Bernhard Wünsch |
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| Rok vydání: | 2017 |
| Předmět: |
Pharmacology
chemistry.chemical_classification Ketone 010405 organic chemistry Stereochemistry Organic Chemistry Pharmaceutical Science chemistry.chemical_element 01 natural sciences Biochemistry Affinities Reductive amination 0104 chemical sciences Chemistry 010404 medicinal & biomolecular chemistry chemistry Drug Discovery Fluorine Side chain Molecular Medicine NMDA receptor Selectivity Receptor |
| Zdroj: | MedChemComm. 8:975-981 |
| ISSN: | 2040-2511 2040-2503 |
| DOI: | 10.1039/c6md00621c |
| Popis: | The influence of an F-atom in the side chain of benzo[7]annulen-7-amines on the affinity towards GluN2B subunit containing NMDA receptors and the selectivity over related receptors was investigated. The synthesis of 5a and 5b was performed by reductive amination of the ketone 6 with primary alkanamines 14a and 14b bearing an F-atom in β-position. The GluN2B affinities of non-fluorinated and fluorinated ligands 4 and 5 are almost identical. The low impact of the F-atom on GluN2B affinity was unexpected, as it influences several chemical and physicochemical properties of the ligands. However, introduction of the F-atom led to reduced selectivity over σ receptors. Whereas 5a and 5b display still a 2–3-fold preference for GluN2B over σ1 receptors, they show almost the same affinity to GluN2B and σ2 receptors. |
| Databáze: | OpenAIRE |
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