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ID: ALA1132792

Journal: Bioorg Med Chem Lett

Title: Syntheses of optically pure beta-hydroxyaspartate derivatives as glutamate transporter blockers.

Authors: Shimamoto K, Shigeri Y, Yasuda-Kamatani Y, Lebrun B, Yumoto N, Nakajima T.

Abstract: DL-threo-beta-benzyloxyaspartate (DL-TBOA) is a non-transportable blocker of the glutamate transporters that serves as an indispensable tool for the investigation of the physiological roles of the transporters. To examine the precise interaction between a blocker and the transporters, we synthesized the optically pure isomers (L- and D-TBOA) and its erythro-isomers. L-TBOA is the most potent blocker for the human excitatory amino acid transporters (EAAT1-3), while D-TBOA revealed a difference in the pharmacophores between EAAT1 and EAAT3. We also synthesized the substituent variants (methyl or naphthylmethyl derivatives) of L-TBOA. The results obtained here suggest that bulky substituents are crucial for non-transportable blockers.

CiteXplore: 11078189

DOI: 10.1016/s0960-894x(00)00487-x