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Updated: May 5, 2026

Methods for the Discovery of Novel Compounds Modulating a Gamma-Aminobutyric Acid Receptor Type A Neurotransmission
Published on: August 16, 2018
Synthesis and biological evaluation of biphenyl amides that modulate the US28 receptor
Ana Kralj1, Elif Kurt, Nuska Tschammer
1Department Chemie und Pharmazie, Pharmazeutische Chemie, Friedrich-Alexander-Universität Erlangen-Nürnberg, Schuhstraße 19, 91052 Erlangen (Germany).
Abstract:
To prepare and biologically evaluate 38 new potential US28 allosteric modulators, we employed a straightforward synthetic route involving radical arylation. The study was based on a former lead structure but with the dihydroisoquinolinone moiety replaced by substituted biphenyls. The investigation of structure-activity relationships among the new biphenyl-derived ligands led to a preliminary pharmacophore model and the discovery of four promising candidates with full inverse agonist properties.
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