Structure–activity relationship study of pyridazine derivatives as glutamate transporter EAAT2 activators

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