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Bioorg Med Chem Lett. 2005 Nov 15;15(22):4985-8.

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 information

1
Chemical and Screening Sciences, Wyeth Research, CN 8000, Princeton, NJ 08543, USA. greenfa@wyeth.com

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.

PMID:
16165356
DOI:
10.1016/j.bmcl.2005.08.003
[Indexed for MEDLINE]

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