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Synthesis and preliminary pharmacological evaluation of novel derivatives of L-beta-threo-benzylaspartate as inhibitors of the neuronal glutamate transporter EAAT3.

ABSTRACT: A series of beta-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 beta-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-position of the aromatic ring of beta-benzylaspartate can increase the potency with which the analogues inhibit EAAT3.

SUBMITTER: Mavencamp TL

PROVIDER: S-EPMC2631431 | biostudies-literature | 2008 Aug

REPOSITORIES: biostudies-literature

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Synthesis and preliminary pharmacological evaluation of novel derivatives of L-beta-threo-benzylaspartate as inhibitors of the neuronal glutamate transporter EAAT3.

Mavencamp Terri L TL Rhoderick Joseph F JF Bridges Richard J RJ Esslinger C Sean CS

Bioorganic & medicinal chemistry 20080708 16

A series of beta-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 beta-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 ...[more]

PMID: 18650095

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