2. Academic Validation
  3. Discovery of 4-(phenoxymethyl)-1H-1,2,3-triazole derivatives as novel xanthine oxidase inhibitors

Discovery of 4-(phenoxymethyl)-1H-1,2,3-triazole derivatives as novel xanthine oxidase inhibitors

  • Bioorg Med Chem Lett. 2022 Mar 15;60:128582. doi: 10.1016/j.bmcl.2022.128582.
Ting-Jian Zhang 1,  Yi Zhang 1,  Zhen-Hao Zhang 1,  Zhao-Ran Wang 1,  Xu Zhang 1,  Sen-Sen Hu 1,  Peng-Fei Lu 1,  Shuai Guo 1,  Fan-Hao Meng 2
Affiliations

Affiliations

  • 1 School of Pharmacy, China Medical University, 77 Puhe Road, North New Area, Shenyang 110122, China.
  • 2 School of Pharmacy, China Medical University, 77 Puhe Road, North New Area, Shenyang 110122, China. Electronic address: [email protected].
PMID: 35077850 DOI: 10.1016/j.bmcl.2022.128582
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 IC50 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.

Keywords

Ligand efficiency metrics; Structural optimization; Xanthine oxidase inhibitors.

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