Synthesis and biochemical evaluation of N-(4-phenylthiazol-2-yl)benzenesulfonamides as high-affinity inhibitors of kynurenine 3-hydroxylase.

doi:10.1021/JM970467T

Paper

Synthesis and biochemical evaluation of N-(4-phenylthiazol-2-yl)benzenesulfonamides as high-affinity inhibitors of kynurenine 3-hydroxylase.

Published Dec 19, 1997 · S. Röver, A. Cesura, P. Huguenin

Journal of medicinal chemistry

Q1 SJR score

198

Citations

8

Influential Citations

Full textSemantic Scholar

Abstract

In this paper we describe the synthesis, structure-activity relationship (SAR), and biochemical characterization of N-(4-phenylthiazol-2-yl)benzenesulfonamides as inhibitors of kynurenine 3-hydroxylase. The compounds 3,4-dimethoxy-N-[4-(3-nitrophenyl)thiazol-2-yl]benzenesulfonamide 16 (IC50 = 37 nM, Ro-61-8048) and 4-amino-N-[4-[2-fluoro-5-(trifluoromethyl)phenyl]-thiazol-2-yl] benzenesulfonamide 20 (IC50 = 19 nM) were found to be high-affinity inhibitors of this enzyme in vitro. In addition, both compounds blocked rat and gerbil kynurenine 3-hydroxylase after oral administration, with ED50's in the 3-5 mumol/kg range in gerbil brain. In a microdialysis experiment in rats, 16 dose dependently increased kynurenic acid concentration in the extracellular hippocampal fluid. A dose of 100 mumol/kg po led to a 7.5-fold increase in kynurenic acid outflow. These new compounds should allow detailed investigation of the pathophysiological role of the kynurenine pathway after neuronal injury.

Non-RCT

Animal Study

Highly Cited

Study Snapshot

N-(4-phenylthiazol-2-yl)benzenesulfonamides are high-affinity inhibitors of kynurenine 3-hydroxylase, allowing detailed investigation of the kynurenine pathway after neuronal injury.

PopulationOlder adults (50-71 years)

Sample size24

MethodsObservational

OutcomesBody Mass Index projections

ResultsSocial networks mitigate obesity in older groups.

Sign up to use Study Snapshot

Consensus is limited without an account. Create an account or sign in to get more searches and use the Study Snapshot.

Create an account

Paper

Synthesis and biochemical evaluation of N-(4-phenylthiazol-2-yl)benzenesulfonamides as high-affinity inhibitors of kynurenine 3-hydroxylase.

Sign up to use Study Snapshot

References

Citations

Exploring tryptophan metabolism: The transition from disturbed balance to diagnostic and therapeutic potential in metabolic diseases.

Studying tryptophan metabolism in gut microbiota may help understand and treat metabolic diseases, potentially introducing new therapeutic strategies.

The Complex World of Kynurenic Acid: Reflections on Biological Issues and Therapeutic Strategy

Kynurenic acid's biology and therapeutic potential remain unclear, but modulating its production or activity could benefit neurological, psychiatric, inflammatory, and cell protection conditions.

Antibacterial Activity of Transition Metal Mn(II), Co(II), Ni(II) and Cu(II) Complexes Containing Bioactive Ligands

Transition metal Mn(II), Co(II), Ni(II), and Cu(II) complexes with bioactive ligands show antibacterial activity against E.coli and S.aureus.

A tryptophan metabolite modulates the host response to bacterial infection via kainate receptors

3-hydroxy-kynurenine enhances host survival by restricting bacterial expansion in macrophages by targeting kainate-sensitive glutamate receptors.

Interactions of IDO and the Kynurenine Pathway with Cell Transduction Systems and Metabolism at the Inflammation–Cancer Interface

The kynurenine pathway can be targeted to indirectly influence inflammation and cancer development by interacting with other transduction systems, potentially expanding the range of potential anti-inflammatory drugs.

Modulation of T cells by tryptophan metabolites in the kynurenine pathway.

The kynurenine pathway plays a crucial role in adaptive immunity and inflammation, but current treatments for autoimmune disorders and cancer have not achieved expected results.

Therapeutic potential of targeting kynurenine pathway in neurodegenerative diseases.

Targeting the kynurenine pathway shows potential in treating neurodegenerative diseases, with potential improvements in aging and neurodegenerative diseases.