Liver fibrosis is commonly occurred in chronic liver diseases, but there is no approved drug for clinical use. The nuclear receptor peroxisome proliferator-activated receptors (PPARs) could not only regulate metabolic homeostasis but also possess anti-inflammatory and antifibrotic effects, and pan-PPARs agonist was considered as a potential anti-liver fibrosis agent. In this study, a series of novel piperazine pan-PPARs agonists were developed, and the preferred compound displayed potent and well-balanced pan-PPARs agonistic activity. Moreover, compound could dose-dependently stimulate the PPARs target genes expression and showed high selectivity over other related nuclear receptors. Importantly, compound exhibited excellent pharmacokinetic profiles and good anti-liver fibrosis effects in . Collectively, compound holds promise for developing an anti-liver fibrosis agent.

中文翻译：

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哌嗪衍生物作为泛 PPAR 激动剂治疗肝纤维化的设计、合成和生物学评价

肝纤维化常见于慢性肝病，但尚无批准用于临床的药物。核受体过氧化物酶体增殖物激活受体（PPARs）不仅可以调节代谢稳态，还具有抗炎和抗纤维化作用，泛PPARs激动剂被认为是潜在的抗肝纤维化药物。在这项研究中，开发了一系列新型哌嗪泛PPARs激动剂，优选的化合物表现出有效且均衡的泛PPARs激动活性。此外，该化合物可以剂量依赖性地刺激 PPAR 靶基因的表达，并表现出比其他相关核受体更高的选择性。重要的是，该化合物在体内表现出优异的药代动力学特征和良好的抗肝纤维化作用。总的来说，该化合物有望开发出抗肝纤维化药物。