title: Synthesis and biological evaluation of aminomethylphenol derivatives as inhibitors of the murine GABA transporters mGAT1-mGAT4.
abstract: A series of N-substituted aminomethylphenol derivatives was synthesized by reductive amination. To study the inhibitory potency of the target compounds at the murine GABA transporters (mGAT1-mGAT4), a [(3)H]GABA uptake test system in a 96-well format based on HEK cells stably expressing mGAT1-mGAT4 was established and validated. Inhibitory potencies at mGAT1-mGAT4 in the micromolar range and a slight subtype selectivity for mGAT3 were observed for the synthesized aminomethylphenol derivatives. Among the compounds investigated 5-n-dodecylaminomethyl-2-methoxyphenol (21) was found to be most potent with an IC(50) value at mGAT3 of about 3muM.
authors.affiliation: Department of Pharmacy - Centre of Drug Research, Ludwig-Maximilians-Universität München, Butenandtstrasse 5-13, 81377 Munich, Germany.
authors.forename: Andrea
authors.initials: A
authors.lastname: Kragler
authors.forename: Georg
authors.initials: G
authors.lastname: Höfner
authors.forename: Klaus T
authors.initials: KT
authors.lastname: Wanner
mesh_terms: D000818:Animals; D001596:Benzylamines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D050485:GABA Plasma Membrane Transport Proteins / Q000145:classification / Q000378:metabolism; D058805:GABA Uptake Inhibitors; D006801:Humans; D008745:Methylation; D051379:Mice; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D001596:Benzylamines; D050485:GABA Plasma Membrane Transport Proteins; D058805:GABA Uptake Inhibitors; D005680:gamma-Aminobutyric Acid