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 Citationer (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.

Originalsprog	Engelsk
Tidsskrift	Journal of Medicinal Chemistry
Vol/bind	52
Udgave nummer	4
Sider (fra-til)	912-915
ISSN	0022-2623
DOI	https://doi.org/10.1021/jm8013458
Status	Udgivet - 2009

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author = "Jensen, {Anders Asbj{\o}rn} and Erichsen, {Mette Navy} and Nielsen, {Christina W{\o}hlk} and Stensb{\o}l, {Tine Bryan} and Jan Kehler and Lennart Bunch",

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AU - Jensen, Anders Asbjørn

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AU - Stensbøl, Tine Bryan

AU - Kehler, Jan

AU - Bunch, Lennart

PY - 2009

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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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JO - Journal of Medicinal Chemistry

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ER -

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

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