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Synthesis and pharmacological evaluation of fluorinated benzo[7]annulen‐7‐amines as GluN2B‐selective NMDA receptor antagonists
Author(s) -
Thum Simone,
Schepmann Dirk,
Reinoso Raquel F.,
Alvarez Inés,
Ametamey Simon M.,
Wünsch Bernhard
Publication year - 2019
Publication title -
journal of labelled compounds and radiopharmaceuticals
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.432
H-Index - 47
eISSN - 1099-1344
pISSN - 0362-4803
DOI - 10.1002/jlcr.3718
Subject(s) - chemistry , norepinephrine transporter , herg , selectivity , nmda receptor , stereochemistry , transporter , pharmacology , serotonin , receptor , biochemistry , biophysics , potassium channel , medicine , gene , biology , catalysis
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 σ 1 and σ 2 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 p K a value of a set fluorinated ligands, bearing the fluorine atom in different positions, was determined.