175777-22-7

Usage

Uses

Used in Pharmaceutical Industry:
(R)-4-Chlorokynurenine is used as a precursor for the synthesis of Kynurenic Acid, which is known for its antiexcitotoxic and anticonvulsant properties. This makes it a valuable compound in the development of treatments for neurological disorders and conditions related to excitotoxicity.
Used in Neurological Applications:
(R)-4-Chlorokynurenine is used as a therapeutic agent for neurological conditions due to its antiexcitotoxic and anticonvulsant properties. It can potentially be employed in the treatment of epilepsy, neurodegenerative diseases, and other conditions involving excitotoxicity.
Used in Research and Development:
(R)-4-Chlorokynurenine is used as a research compound to study the metabolic pathways of tryptophan and the role of Kynurenine in various biological processes. This can contribute to a better understanding of the underlying mechanisms of neurological disorders and the development of novel therapeutic strategies.

Upstream product

• 108-42-9 3-chloro-aniline 
• 64605-37-4 1-(2-amino-4-chlorophenyl)-2-chloroethan-1-one 
• 73-22-3 L-Tryptophan 
• 33468-35-8 6-chloro-DL-tryptophan 
• 153042-33-2 tert-butyl (5-chloro-2-iodophenyl)carbamate 
• 89-63-4 4-Chloro-2-nitroaniline 
• 6828-35-9 5-chloro-2-iodoaniline 
• 5446-05-9 4-chloro-2-nitroiodobenzene 
• 153042-35-4 (S)-4-[2-(2-Amino-4-chloro-phenyl)-2-oxo-ethyl]-5-oxo-oxazolidine-3-carboxylic acid benzyl ester 

Relevant academic research and scientific papers

4-Chloro-l-kynurenine as fluorescent amino acid in natural peptides

4-Chloro-l-kynurenine (3-(4-chloroanthraniloyl)-l-alanine, l-4-ClKyn), an amino acid known as a prospective antidepressant, was recently for the first time found in nature in the lipopeptide antibiotic taromycin. Here, we report another instance of its identification in a natural product: 4-chloro-l-kynurenine was isolated from acidic hydrolysis of a new complex peptide antibiotic INA-5812. l-4-ClKyn is a fluorescent compound responsible for the fluorescence of the above antibiotic. Whereas fluorescence of 4-chlorokynurenine was not reported before, we synthesized the racemic compound and studied its emission in various solvents. Next, we prepared conjugates of dl-4-ClKyn with two suitable energy acceptors, BODIPY FL and 3-(phenylethynyl)perylene (PEPe), and studied fluorescence of the derivatives. 4-Chloro-dl-kynurenine emission is not detected in both conjugates, thus evidencing effective energy transfer. However, BODIPY FL emission in the conjugate is substantially reduced, probably due to collisional or photoinduced charge-transfer-mediated quenching. The intrinsic fluorescence of l-4-ClKyn amino acid in antibiotics paves the way for spectral studies of their mode of action.

Biosynthesis of l-4-Chlorokynurenine, an Antidepressant Prodrug and a Non-Proteinogenic Amino Acid Found in Lipopeptide Antibiotics

l-4-Chlorokynurenine (l-4-Cl-Kyn) is a neuropharmaceutical drug candidate that is in development for the treatment of major depressive disorder. Recently, this amino acid was naturally found as a residue in the lipopeptide antibiotic taromycin. Herein, we report the unprecedented conversion of l-tryptophan into l-4-Cl-Kyn catalyzed by four enzymes in the taromycin biosynthetic pathway from the marine bacterium Saccharomonospora sp. CNQ-490. We used genetic, biochemical, structural, and analytical techniques to establish l-4-Cl-Kyn biosynthesis, which is initiated by the flavin-dependent tryptophan chlorinase Tar14 and its flavin reductase partner Tar15. This work revealed the first tryptophan 2,3-dioxygenase (Tar13) and kynurenine formamidase (Tar16) enzymes that are selective for chlorinated substrates. The substrate scope of Tar13, Tar14, and Tar16 was examined and revealed intriguing promiscuity, thereby opening doors for the targeted engineering of these enzymes as useful biocatalysts.

SYNTHESIS OF 4-CHLOROKYNURENINES AND INTERMEDIATES

The invention relates to an overall enantio-specific synthesis of 4-chlorokynurenine compounds, in particular L-4-chlorokynurenine, with improved yields. Large-scale syntheses are disclosed. The invention also relates to novel intermediates in the synthes

DEUTERATED CHLOROKYNURENINES FOR THE TREATMENT OF NEUROPSYCHIATRIC DISORDERS

Described are deuterated chlorokynurenines and compositions, and their application as pharmaceuticals for the treatment of disease. Methods of modulating N-methyl-D-aspartate (NMDA) receptor activity, methods of treating disorders, including neuropsychiatric disorders such as depression, epilepsy, schizophrenia, and Huntington's Disease, and use of said deuterated chlorokynurenines are also described.

METHODS FOR THE SYNTHESIS OF CHIRAL KYNURENINE COMPOUNDS

Provided are methods for synthesizing compounds, including chiral kynurenine compounds. The methods are suitable for large-scale manufacture and produce the chiral kynurenines compounds in high chemical purity and high chiral purity.

SYNTHESIS OF CHIRAL KYNURENINE COMPOUNDS AND INTERMEDIATES

Provided are methods for the synthesis of compounds including chiral kynurenine compounds, intermediates useful for the synthesis thereof, and related compounds. For example, methods are provided for the synthesis of L-4-chlorokynurenine.

Derivatives of kynurenine as inhibitors of rat brain kynurenine aminotransferase

The structural requirements of the catalytic site of kynurenine aminotransferase (KAT), the enzyme responsible for the conversion of L-kynurenine (KYN) to kynurenic acid (KYNA), were examined using analogs and derivatives of KYN. KYNA production from KYN was monitored in rat brain homogenates and brain tissue slices. Modification of KYN's acylalanine side chain or its ring amino group resulted in compounds which did not substantially affect KYNA synthesis. Ring chlorination in positions 3, 4, 5 and 6 yielded KYN analogs which interfered with KYNA production. L-5-Cl-KYN was the most active of the chlorinated kynurenines, and one of the most potent of several other 5-substituted kynurenines. L-5-Cl-KYN was an excellent substrate of KAT, yielding 6-Cl-KYNA. Finally, in kinetic studies, L-5-Cl-KYN (K(i) = 5.4 μM) was found to have an approximately five times higher affinity to the enzyme than the natural substrate KYN (K(m) = 28 μM).