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Published on: August 16, 2018
Identification of Triazolopyridines as Selective α5-GABAA Receptor Negative Allosteric Modulators by a Hybridization
György Szabó1, Benedek Imre Károlyi1, Ágnes Gyöngyvér Vaskó1
1Chemistry Division, Gedeon Richter Plc, P.O. Box 27, Budapest 10H-1475, Hungary.
Abstract:
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.
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