Identification of Triazolopyridines as Selective α5-GABAA Receptor Negative Allosteric Modulators by a Hybridization Approach

The identification and characterization of novel triazolopyridine derivatives with selective α5 subunit-containing GABAA receptor negative allosteric modulator (NAM) activity are disclosed. As a result of in silico screening of our corporate compound deck, we identified a moderately potent hit that...

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Bibliographic Details
Published in:ACS chemical neuroscience 2023-01, Vol.14 (1), p.148-158
Main Authors: Szabó, György, Károlyi, Benedek Imre, Vaskó, Ágnes Gyöngyvér, Potor, Attila, Vukics, Krisztina, Kapus, Gábor László, Fodor, László, Bobok, Amrita, Vastag, Mónika, Bata, Imre
Format: Article
Language:English
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Summary:The identification and characterization of novel triazolopyridine derivatives with selective α5 subunit-containing GABAA receptor negative allosteric modulator (NAM) activity are disclosed. As a result of in silico screening of our corporate compound deck, we identified a moderately potent hit that was converted to an advanced hit bearing better physicochemical and pharmacological properties using a hybridization approach. Subsequent optimization led to the identification of in vitro potent and subtype-selective α5-GABAA receptor NAMs representing a new chemotype in this area.
ISSN:1948-7193
1948-7193
DOI:10.1021/acschemneuro.2c00608