205309-81-5

Usage

Uses

Used in Pharmaceutical Research:
DL-TBOA is used as a research tool for studying the role of excitatory amino acid transporters (EAATs) in various neurological conditions. Its ability to inhibit glutamate uptake helps researchers understand the mechanisms behind conditions such as epilepsy, stroke, and neurodegenerative diseases.
Used in Neurological Condition Treatment:
DL-TBOA is used as a potential therapeutic agent for the treatment of neurological conditions characterized by hyperexcitability and imbalances in neurotransmitter levels, such as epilepsy and certain neurodegenerative diseases. Its inhibitory effects on EAATs can help regulate the levels of excitatory amino acids in the brain, potentially reducing the severity of symptoms.
Used in Antinociception Studies:
DL-TBOA is used as an agent for inducing antinociception in the second phase of the formalin test in rats. When administered prior to the formalin injection, it has been shown to provide pain relief, which can be useful in the study of pain mechanisms and the development of new pain management strategies.

in vitro

dl-tboa inhibited the uptake of [14c]glutamate in cos-1 cells overexpressing the human excitatory amino acid transporter-1 (eaat1) (ki = 42 μm) with almost the same potency as dl-threo-b-hydroxyaspartate (ki = 58 μm). with regard to the human excitatory amino acid transporter-2 (eaat2), the inhibitory effect of dl-tboa (ki = 5.7 μm) was much more potent than that of dihydrokainate (ki = 79 μm), which is well known as a selective blocker of this subtype. [1].

in vivo

microdialysis administration of 500 μm dl-tboa into the hippocampus increased 3.4- and nine-fold the extracellular levels of aspartate and glutamate, respectively. upon stereotaxic administration it induced neuronal damage dose-dependently in ca1 and dentate gyrus, and convulsive behavior. electroencephalographic recording showed limbic seizures appearance in the hippocampus after dl-tboa infusion. [2].

references

[1] shimamoto k, lebrun b, yasuda-kamatani y, sakaitani m, shigeri y, yumoto n, nakajima t. dl-threo-beta-benzyloxyaspartate, a potent blocker of excitatory amino acid transporters. mol pharmacol. 1998 feb;53(2):195-201.[2] montiel t, camacho a, estrada-sánchez am, massieu l. differential effects of the substrate inhibitor l-trans-pyrrolidine-2,4-dicarboxylate (pdc) and the non-substrate inhibitor dl-threo-beta-benzyloxyaspartate (dl-tboa) of glutamate transporters on neuronal damage and extracellular amino acid levels in rat brain in vivo. neuroscience. 2005;133(3):667-78.

Upstream product

• 544434-65-3 (2S,3S)-2-Amino-3-benzyloxy-succinic acid 1-(7-methoxy-2-oxo-2H-chromen-4-ylmethyl) ester 
• 544434-61-9 (2S,3S)-2-Amino-3-benzyloxy-succinic acid 1-(7-carboxymethoxy-2-oxo-2H-chromen-4-ylmethyl) ester 
• 316172-60-8 4-(1-benzyloxy-allyl)-2,2-dimethyl-oxazolidine-3-carboxylic acid tert-butyl ester 
• 316172-62-0 (2S,3R)-2-Benzyloxy-3-tert-butoxycarbonylamino-4-hydroxy-butyric acid methyl ester 
• 316172-64-2 (2S,3S)-2-Benzyloxy-3-tert-butoxycarbonylamino-succinic acid 1-methyl ester 
• 100-51-6 benzyl alcohol 
• 316172-63-1 (2R,3R)-2-Benzyloxy-3-tert-butoxycarbonylamino-4-hydroxy-butyric acid methyl ester 

Relevant academic research and scientific papers

Chemoenzymatic Synthesis of ortho-, meta-, and para-Substituted Derivatives of L -threo-3-Benzyloxyaspartate, An Important Glutamate Transporter Blocker

A simple, three-step chemoenzymatic synthesis of L-threo-3-benzyloxyaspartate (L-TBOA), as well as L-TBOA derivatives with F, CF3, and CH3 substituents at the aromatic ring, starting from dimethyl acetylenedicarboxylate was investiga

Synthesis and photoreactivity of caged blockers for glutamate transporters

L-TBOA (L-threo-β-benzyloxyaspartate) is, so far, the most potent non-transportable blocker for glutamate transporters. We synthesized α-CMCM-L-TBOA (1a) possessing [7-(carboxymethoxy)coumarin-4-yl]methyl ester as a caging group. α-CMCM-L-TBOA (1a) is biologically inactive until UV irradiation and the photolysis of 1a immediately released L-TBOA to show glutamate uptake inhibition. The photoreactivity of the coumarin-type caging group was superior to that of the o-nitrobenzyl-type caging group.

beta -hydroxyaspartic acid derivatives

The present invention provides blockers for glutamate transporters. During a series of syntheses searching for glutamate uptake inhibition in Xenopus oocytes injected with bovine glutamate transporter genes (BGLAST), we obtained beta -hydroxyaspartic acid derivatives of the following chemical formula (1): wherein R represents an aromatic acyl group which may be substituted on the ring, a straight or branched lower aliphatic acyl group, an aryl group which may be substituted on the ring, an aralkyl group which may be substituted on the ring, or a straight or branched lower alkyl group; and salts thereof. These compounds are blockers of glutamate transporters, which are useful for the understanding of the function of glutamate transporters and show promise for the treatment of various neurodegenerative diseases.

Syntheses of optically pure β-hydroxyaspartate derivatives as glutamate transporter blockers

DL-threo-β-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. (C) 2000 Elsevier Science Ltd.