title: Development of imidazole alkanoic acids as mGAT3 selective GABA uptake inhibitors.
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.
authors.affiliation: Department of Pharmacy, Center for Drug Research, Ludwig-Maximilians-University Munich, Butenandtstr. 5-13, D-81377 Munich, Germany.
authors.forename: Silke
authors.initials: S
authors.lastname: Hack
authors.forename: Babette
authors.initials: B
authors.lastname: Wörlein
authors.forename: Georg
authors.initials: G
authors.lastname: Höfner
authors.forename: Jörg
authors.initials: J
authors.lastname: Pabel
authors.forename: Klaus T
authors.initials: KT
authors.lastname: Wanner
mesh_terms: D002460:Cell Line; D050485:GABA Plasma Membrane Transport Proteins / Q000737:chemistry / Q000378:metabolism*; D058805:GABA Uptake Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D007093:Imidazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D015394:Molecular Structure; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013379:Substrate Specificity
chemical_list: C559777:1H-imidazol-4-ylacetic acid; D050485:GABA Plasma Membrane Transport Proteins; D058805:GABA Uptake Inhibitors; D007093:Imidazoles