Discovery of the First Selective Inhibitor of Excitatory Amino Acid Transporter Subtype 1
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-...
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Published in | Journal of medicinal chemistry Vol. 52; no. 4; pp. 912 - 915 |
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Main Authors | , , , , , |
Format | Journal Article |
Language | English |
Published |
WASHINGTON
American Chemical Society
26.02.2009
Amer Chemical Soc |
Subjects | |
Online Access | Get full text |
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Summary: | 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. |
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ISSN: | 0022-2623 1520-4804 |
DOI: | 10.1021/jm8013458 |