Back to Search
Start Over
Discovery of 4-(phenoxymethyl)-1H-1,2,3-triazole derivatives as novel xanthine oxidase inhibitors.
- Source :
-
Bioorganic & medicinal chemistry letters [Bioorg Med Chem Lett] 2022 Mar 15; Vol. 60, pp. 128582. Date of Electronic Publication: 2022 Jan 22. - Publication Year :
- 2022
-
Abstract
- A series of 4-(phenoxymethyl)-1H-1,2,3-triazole derivatives were designed, synthesized, and evaluated for their xanthine oxidase (XO) inhibitory activities. Among these compounds, 9m emerged as the most effective XO inhibitor with an IC <subscript>50</subscript> value of 0.70 μM, which was approximately 14-fold more potent than allopurinol. Additionally, compound 9m displayed favorable drug-like properties with ligand efficiency (LE) and lipophilic ligand efficiency (LLE) values of 0.33 and 3.41, respectively. We further explored the binding mode of 9m in complex with XO by molecular docking and molecular dynamics studies. In vivo hypouricemic studies also suggested that 9m could effectively lower the serum uric acid levels of rat. In summary, compound 9m could be a promising lead for further development of XO inhibitors.<br /> (Copyright © 2022 Elsevier Ltd. All rights reserved.)
- Subjects :
- Animals
Dose-Response Relationship, Drug
Enzyme Inhibitors chemical synthesis
Enzyme Inhibitors chemistry
Hyperuricemia chemically induced
Hyperuricemia drug therapy
Hyperuricemia metabolism
Ligands
Models, Molecular
Molecular Structure
Oxonic Acid
Rats
Structure-Activity Relationship
Triazoles chemical synthesis
Triazoles chemistry
Uric Acid antagonists & inhibitors
Uric Acid blood
Xanthine Oxidase metabolism
Drug Discovery
Enzyme Inhibitors pharmacology
Triazoles pharmacology
Xanthine Oxidase antagonists & inhibitors
Subjects
Details
- Language :
- English
- ISSN :
- 1464-3405
- Volume :
- 60
- Database :
- MEDLINE
- Journal :
- Bioorganic & medicinal chemistry letters
- Publication Type :
- Academic Journal
- Accession number :
- 35077850
- Full Text :
- https://doi.org/10.1016/j.bmcl.2022.128582