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Development of imidazole alkanoic acids as mGAT3 selective GABA uptake inhibitors.

European journal of medicinal chemistry (2011-03-01)
Silke Hack, Babette Wörlein, Georg Höfner, Jörg Pabel, Klaus T Wanner
ABSTRACT

A new series of potential GABA uptake inhibitors starting from of 1H-imidazol-4-ylacetic acid with the carboxylic acid side chain originating from different positions and varying in length have been synthesized and tested for the inhibitory potency at the four GABA uptake transporters mGAT1-4 stably expressed in HEK cells. Further two bicyclic compounds with a rigidified carboxylic acid side chain were included in this study. The results of the biological tests indicated that most ω-imidazole alkanoic and alkenoic acid derivatives exhibit the highest potencies as GABA uptake inhibitors at mGAT3.

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