Document Detail

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.
MedLine Citation:
PMID:  16165356     Owner:  NLM     Status:  MEDLINE    
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.
Alexander Greenfield; Cristina Grosanu; John Dunlop; Beal McIlvain; Tikva Carrick; Brian Jow; Qiang Lu; Dianne Kowal; John Williams; John Butera
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Bioorganic & medicinal chemistry letters     Volume:  15     ISSN:  0960-894X     ISO Abbreviation:  Bioorg. Med. Chem. Lett.     Publication Date:  2005 Nov 
Date Detail:
Created Date:  2005-10-05     Completed Date:  2005-12-23     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9107377     Medline TA:  Bioorg Med Chem Lett     Country:  England    
Other Details:
Languages:  eng     Pagination:  4985-8     Citation Subset:  IM    
Chemical and Screening Sciences, Wyeth Research, CN 8000, Princeton, NJ 08543, USA.
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MeSH Terms
Aspartic Acid / chemistry*
Biological Transport / drug effects
Ether, Ethyl / chemistry*
Excitatory Amino Acid Transporter 2 / antagonists & inhibitors*,  metabolism
Fluorenes / chemistry*
Inhibitory Concentration 50
Molecular Structure
Propionic Acids / chemical synthesis,  chemistry*
Structure-Activity Relationship
beta-Alanine / analogs & derivatives*,  chemical synthesis,  chemistry*
Reg. No./Substance:
0/Excitatory Amino Acid Transporter 2; 0/Fluorenes; 0/Propionic Acids; 107-95-9/beta-Alanine; 56-84-8/Aspartic Acid; 60-29-7/Ether, Ethyl; 79-09-4/propionic acid; 86-73-7/fluorene

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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