Discovery of the first selective inhibitor of excitatory amino acid transporter subtype 1

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Anders Asbjørn Jensen, Mette Navy Erichsen, Christina Wøhlk Nielsen, Tine Bryan Stensbøl, Jan Kehler, Lennart Bunch

The discovery of the first class of subtype-selective inhibitors of the human excitatory amino acid transporter subtype 1 (EAAT1) and its rat orthologue GLAST is reported. An opening structure-activity relationship of 25 analogues is presented that addresses the influence of substitutions at the 4- and 7-positions of the parental skeleton 2-amino-5-oxo-5,6,7,8-tetrahydro-4H-chromene-3-carbonitrile. The most potent analogue 1o displays high nanomolar inhibitory activity at EAAT1 and a >400-fold selectivity over EAAT2 and EAAT3, making it a highly valuable pharmacological tool.
Original languageEnglish
JournalJournal of Medicinal Chemistry
Volume52
Issue number4
Pages (from-to)912-915
ISSN0022-2623
DOIs
Publication statusPublished - 2009

ID: 10245107