2. Academic Validation
  3. Design, synthesis, and biological evaluation of imidazolidinone derivatives as potent PPARα/δ agonists for the treatment of cholestatic liver diseases

Design, synthesis, and biological evaluation of imidazolidinone derivatives as potent PPARα/δ agonists for the treatment of cholestatic liver diseases

  • Eur J Med Chem. 2025 Mar 15:286:117284. doi: 10.1016/j.ejmech.2025.117284.
Zhuoxin Fu 1,  Xin Liu 1,  Wenhui Yu 1,  Yufan Kuang 1,  Fengqin Wang 1,  Zhiqiang Qian 1,  Qinglong Xu 2,  Liang Dai 3,  Zhiqi Feng 4
Affiliations

Affiliations

  • 1 Jiangsu Key Laboratory of Drug Discovery for Metabolic Disease, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, 210009, China.
  • 2 Jiangsu Key Laboratory of Drug Discovery for Metabolic Disease, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, 210009, China. Electronic address: qlxu@cpu.edu.cn.
  • 3 Jiangsu Key Laboratory of Drug Discovery for Metabolic Disease, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, 210009, China. Electronic address: dailiang@cpu.edu.cn.
  • 4 Jiangsu Key Laboratory of Drug Discovery for Metabolic Disease, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, 210009, China. Electronic address: fzq@cpu.edu.cn.
PMID: 39827490 DOI: 10.1016/j.ejmech.2025.117284
Abstract

Cholestatic liver disease (CLD) represents a significant and growing public health concern, and there is a lack of effective therapeutic drug in clinical practice. Peroxisome proliferator-activator receptors α/δ (PPARα/δ) are regarded as potential therapeutic targets for CLD. In this study, a series of novel imidazolidinone PPARα/δ agonists were developed, and the preferred compound 8 displayed potent and well-balanced agonistic activity. Compound 8 showed high selectivity over Other related nuclear receptors and effectively regulated the PPARα/δ target genes expression in mice. Notably, compound 8 demonstrated good pharmacokinetic profiles and potent in vivo anti-CLD effects. Collectively, compound 8 holds promise for developing an anti-CLD agent.

Keywords

Cholestatic liver disease; Imidazolidinone; Nuclear receptor; PPARs.

Figures
Products