Do GluN2B subunit containing NMDA receptors tolerate a fluorine atom in the phenylalkyl side chain?

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 and was performed by reductive amination of the ketone with primary alkanamines and bearing an F-atom in β-position. The GluN2B affinities of non-fluorinated and fluorinated ligands and 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 receptors. Whereas and display still a 2-3-fold preference for GluN2B over receptors, they show almost the same affinity to GluN2B and receptors.