480439-73-4

Basic information

• Product Name: (3S)-3-[[3-[[4-(TRIFLUOROMETHYL)BENZOYL]AMINO]PHENYL]METHOXY]-L-ASPARTIC ACID
• Synonyms: (3S)-3-[[3-[[4-(TRIFLUOROMETHYL)BENZOYL]AMINO]PHENYL]METHOXY]-L-ASPARTIC ACID;TFB-TBOA
• CAS NO: 480439-73-4
• Molecular Formula: C19H17F3N2O6
• Molecular Weight: 426.34
• Mol File: 480439-73-4.mol

Chemical Properties

• Boiling Point: 513.6±50.0 °C(Predicted)
• Appearance: /
• Density: 1.500±0.06 g/cm3(Predicted)
• Storage Temp.: Store at -20°C
• PKA: 2.05±0.27(Predicted)
• CAS DataBase Reference: (3S)-3-[[3-[[4-(TRIFLUOROMETHYL)BENZOYL]AMINO]PHENYL]METHOXY]-L-ASPARTIC ACID(CAS DataBase Reference)
• NIST Chemistry Reference: (3S)-3-[[3-[[4-(TRIFLUOROMETHYL)BENZOYL]AMINO]PHENYL]METHOXY]-L-ASPARTIC ACID(480439-73-4)
• EPA Substance Registry System: (3S)-3-[[3-[[4-(TRIFLUOROMETHYL)BENZOYL]AMINO]PHENYL]METHOXY]-L-ASPARTIC ACID(480439-73-4)

Safety Data

• Hazardous Substances Data: 480439-73-4(Hazardous Substances Data)

Usage

Uses

TFB-TBOA is a novel glutamate transporter blocker.

Biological Activity

High affinity, selective blocker of glial glutamate transporters EAAT1 and EAAT2 (IC 50 values are 17, 22 and 300 nM for EAAT2, EAAT1 and EAAT3 respectively). Displays no activity on a wide range of neurotransmitter receptors and transporters. Induces convulsions following i.c.v. administration in mice.

Upstream product

• 329-15-7 4-trifluoromethyl-phenyl acetyl chloride 
• 1877-77-6 3-aminobenzenemethanol 
• 1178630-91-5 N-(3-(hydroxymethyl)phenyl)-4-(trifluoromethyl)benzamide 

Relevant articles and documents

Concise Asymmetric Synthesis and Pharmacological Characterization of All Stereoisomers of Glutamate Transporter Inhibitor TFB-TBOA and Synthesis of EAAT Photoaffinity Probes

Glutamate is the major excitatory neurotransmitter in the mammalian brain. Its rapid clearance after the release into the synaptic cleft is vital in order to avoid toxic effects and is ensured by several transmembrane transport proteins, so-called excitatory amino acid transporters (EAATs). Impairment of glutamate removal has been linked to several neurodegenerative diseases and EAATs have therefore received increased attention as therapeutic targets. O-Benzylated l-threo-β-hydroxyaspartate derivatives have been developed previously as highly potent inhibitors of EAATs with TFB-TBOA ((2S,3S)-2-amino-3-((3-(4-(trifluoromethyl)benzamido)benzyl)oxy)succinic acid) standing out as low-nanomolar inhibitor. We report the stereoselective synthesis of all four stereoisomers of TFB-TBOA in less than a fifth of synthetic steps than the published route. For the first time, the inhibitory activity and isoform selectivity of these TFB-TBOA enantio- and diastereomers were assessed on human glutamate transporters EAAT1-3. Furthermore, we synthesized potent photoaffinity probes based on TFB-TBOA using our novel synthetic strategy.

Rapid chemoenzymatic route to glutamate transporter inhibitor l-TFB-TBOA and related amino acids

The complex amino acid (l-threo)-3-[3-[4-(trifluoromethyl)benzoylamino]benzyloxy]aspartate (l-TFB-TBOA) and its derivatives are privileged compounds for studying the roles of excitatory amino acid transporters (EAATs) in regulation of glutamatergic neurotransmission, animal behavior, and in the pathogenesis of neurological diseases. The wide-spread use of l-TFB-TBOA stems from its high potency of EAAT inhibition and the lack of off-target binding to glutamate receptors. However, one of the main challenges in the evaluation of l-TFB-TBOA and its derivatives is the laborious synthesis of these compounds in stereoisomerically pure form. Here, we report an efficient and step-economic chemoenzymatic route that gives access to enantio- and diastereopure l-TFB-TBOA and its derivatives at multigram scale.