Title of article :
Synthesis and biological activities of aryl-ether-, biaryl-, and fluorene-aspartic acid and diaminopropionic acid analogs as potent inhibitors of the high-affinity glutamate transporter EAAT-2
Author/Authors :
Alexander Greenfield، نويسنده , , Cristina Grosanu، نويسنده , , John Dunlop، نويسنده , , Beal McIlvain، نويسنده , , Tikva Carrick، نويسنده , , Brian Jow، نويسنده , , Qiang Lu، نويسنده , , Dianne Kowal، نويسنده , , John Williams، نويسنده , , John Butera، نويسنده ,
Abstract :
Excitatory amino acid transporters (EAATs) play a pivotal role in maintaining glutamate homeostasis in the mammalian central nervous system, with the EAAT-2 subtype thought to be responsible for the bulk of the glutamate uptake in forebrain regions. A complete elucidation of the functional role of EAAT-2 has been hampered by the lack of potent and selective pharmacological tools. In this study, we describe the synthesis and biological activities of novel aryl-ether, biaryl-, and fluorene-aspartic acid and diaminopropionic acid analogs as potent inhibitors of EAAT-2. Compound (16) represents one of the most potent (IC50 = 85 ± 5 nM) and selective inhibitors of EAAT-2 identified to date.
