Synthesis and preliminary pharmacological evaluation of novel derivatives of l-β-threo-benzylaspartate as inhibitors of the neuronal glutamate transporter EAAT3

A series of β-benzylaspartate derivatives were prepared from N-trityl-l-aspartate dimethyl ester and evaluated as inhibitors of neuronal glutamate transporter EAAT3. The result of the structure–activity studies suggests that the position occupied by the aromatic ring of β-benzylaspartate within the binding site of EAAT3 may be different from that occupied by comparable groups in previously identified inhibitors, such as l-threo-benzyloxy aspartate (TBOA). Further, halogen substitutions at the 3-postition of the aromatic ring of β-benzylaspartate can increase the potency with which the analogues inhibit EAAT3.

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