Document Report Card

ID: ALA1140931

Journal: J Med Chem

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

Authors: Jensen AA, Erichsen MN, Nielsen CW, Stensbøl TB, Kehler J, Bunch L.

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.

CiteXplore: 19161278

DOI: 10.1021/jm8013458