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Synthesis and pharmacological evaluation of fluorinated benzo[7]annulen-7-amines as GluN2B-selective NMDA receptor antagonists.

Simone ThumDirk SchepmannRaquel F ReinosoInés AlvarezSimon M AmetameyBernhard Wünsch
Published in: Journal of labelled compounds & radiopharmaceuticals (2020)
Because of their neuroprotective potential, GluN2B-selective ligands are of great interest for the treatment of various neurological and neurodegenerative disorders. Fluorinated benzo[7]annulen-7-amines, capable for PET, were synthesized by combining fluorinated phenylalkylamines with differently substituted ketones. Relationships between substitution pattern and GluN2B affinity as well as selectivity towards σ1 and σ2 receptors were investigated. Two promising ligands (18a and 20c) were selected for further pharmacological evaluation. Besides a slight serotonin transporter (SERT), norepinephrine transporter (NET), and hERG affinity, they did not show interaction with other targets. Furthermore, the pKa value of a set fluorinated ligands, bearing the fluorine atom in different positions, was determined.
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