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

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

doi:10.1021/jm8013458

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

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

67 Citations (Scopus)

Abstract

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 language	English
Journal	Journal of Medicinal Chemistry
Volume	52
Issue number	4
Pages (from-to)	912-915
ISSN	0022-2623
DOIs	https://doi.org/10.1021/jm8013458
Publication status	Published - 2009

Keywords

Former Faculty of Pharmaceutical Sciences

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10.1021/jm8013458

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AU - Stensbøl, Tine Bryan

AU - Kehler, Jan

AU - Bunch, Lennart

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AB - 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.

KW - Former Faculty of Pharmaceutical Sciences

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

Abstract

Keywords

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