2-(4-Fluorophenyl)-1H-benzo[d]imidazole as a Promising Template for the Development of Metabolically Robust, α1β2γ2GABA-A Receptor-Positive Allosteric Modulators.

ABSTRACT: Modulation of α1β2γ2GABA-A receptor subpopulation expressed in the basal ganglia region is a conceptually novel mode of pharmacological strategy that offers prospects to tackle a variety of neurological dysfunction. Although clinical findings provided compelling evidence for the validity of this strategy, the current chemical space of molecules able to modulate the α1/γ2 interface of the GABA-A receptor is limited to imidazo[1,2-a]pyridine derivatives that undergo rapid biotransformation. In response to a deficiency in the chemical repertoire of GABA-A receptors, we identified a series of 2-(4-fluorophenyl)-1H-benzo[d]imidazoles as positive allosteric modulators (PAMs) with improved metabolic stability and reduced potential for hepatotoxicity, where lead molecules 9

SUBMITTER: Marcinkowska M 

PROVIDER: S-EPMC10020958 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature