Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
1372541 | Bioorganic & Medicinal Chemistry Letters | 2011 | 4 Pages |
Abstract
Excitatory amino acid transporter 2 (EAAT2) is the major glutamate transporter and functions to remove glutamate from synapses. A thiopyridazine derivative has been found to increase EAAT2 protein levels in astrocytes. A structure–activity relationship study revealed that several components of the molecule were required for activity, such as the thioether and pyridazine. Modification of the benzylthioether resulted in several derivatives (7-13, 7-15 and 7-17) that enhanced EAAT2 levels by >6-fold at concentrations <5 μM after 24 h. In addition, one of the derivatives (7-22) enhanced EAAT2 levels 3.5–3.9-fold after 24 h with an EC50 of 0.5 μM.
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Related Topics
Physical Sciences and Engineering
Chemistry
Organic Chemistry
Authors
Xuechao Xing, Ling-Chu Chang, Qiongman Kong, Craig K. Colton, Liching Lai, Marcie A. Glicksman, Chien-Liang Glenn Lin, Gregory D. Cuny,