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

摘要

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.