1. Academic Validation
  2. Synthesis and bioevaluation of 1-phenylimidazole-4-carboxylic acid derivatives as novel xanthine oxidoreductase inhibitors

Synthesis and bioevaluation of 1-phenylimidazole-4-carboxylic acid derivatives as novel xanthine oxidoreductase inhibitors

  • Eur J Med Chem. 2020 Jan 15;186:111883. doi: 10.1016/j.ejmech.2019.111883.
Haiyan Zhou 1 Xiaolei Li 1 Yuanyuan Li 1 Xinying Zhu 1 Lei Zhang 1 Jing Li 2
Affiliations

Affiliations

  • 1 School of Biology and Biological Engineering, South China University of Technology, Guangzhou, 510006, PR China.
  • 2 School of Biology and Biological Engineering, South China University of Technology, Guangzhou, 510006, PR China. Electronic address: lij@scut.edu.cn.
Abstract

As part of a continuing study, we designed and synthesized four series of 1-phenylimidazole-4-carboxylic acid derivatives as xanthine oxidoreductase (XOR) inhibitors, evaluated their in vitro inhibitory potencies against XOR and hypouricemic effects in mice, and determined their structure-activity relationships (SARs). Most of the compounds exhibited in vitro XOR inhibition at the nanomolar level. In comparison to febuxostat (half-maximal inhibitory concentration [IC50] value of 7.0 nM), compounds Ie and IVa exhibited the most promising XOR inhibitory effects with IC50 values of 8.0 and 7.2 nM, respectively. In the potassium oxonate/hypoxanthine-induced acute and long-term hyperuricemia mouse models, compounds Ie and IVa displayed significant hypouricemic potencies (P < 0.05), that were slightly weaker than and similar to febuxostat, respectively. More interestingly, both compounds showed a capacity to improve kidney damage by decreasing creatinine and urea nitrogen levels compared to the long-term hyperuricemia mouse group (P < 0.05), while febuxostat showed no significant effect.

Keywords

1-Phenylimidazole-4-carboxylic acid; Hypouricemic; Xanthine oxidoreductase inhibitors.

Figures
Products