Synthesis and preliminary pharmacological evaluation of novel derivatives of L-beta-threo-benzylaspartate as inhibitors of the neuronal glutamate transporter EAAT3.
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.
Mavencamp
Terri L
TL
NIH-COBRE Center for Structural and Functional Neuroscience, Department of Biomedical & Pharmaceutical Sciences, The University of Montana, Missoula, MT 59812, USA.
Rhoderick
Joseph F
JF
Bridges
Richard J
RJ
Esslinger
C Sean
CS
D000818:Animals; D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D002460:Cell Line; D050580:Excitatory Amino Acid Transporter 3 / Q000037:antagonists & inhibitors* / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D008958:Models, Molecular; D009474:Neurons / Q000187:drug effects; D013329:Structure-Activity Relationship
D050580:Excitatory Amino Acid Transporter 3; C493400:SLC1A1 protein, human; C120673:benzyloxyaspartate; D001224:Aspartic Acid