Bioorganic and Medicinal Chemistry Letters p. 222 - 229 (2018)
Update date:2022-09-26
Topics:
Chen, Jun
Peng, Zhangzhe
Lu, Miaomiao
Xiong, Xuan
Chen, Zhuo
Li, Qianbin
Cheng, Zeneng
Jiang, Dejian
Tao, Lijian
Hu, Gaoyun
Oxidative stress, inflammation and fibrosis can cause irreversible damage on cell structure and function of kidney and are key pathological factors in Diabetic Nephropathy (DN). Therefore, multi-target agents are urgently need for the clinical treatment of DN. Using Pirfenidone as a lead compound and based on the previous research, two novel series (5-trifluoromethyl)-2(1H)-pyridone analogs were designed and synthesized. SAR of (5-trifluoromethyl)-2(1H)-pyridone derivatives containing nitrogen heterocyclic ring have been established for in vitro potency. In addition, compound 8, a novel agent that act on multiple targets of anti-DN with IC50 of 90 μM in NIH3T3 cell lines, t1/2 of 4.89 ± 1.33 h in male rats and LD50 > 2000 mg/kg in mice, has been advanced to preclinical studies as an oral treatment for DN.
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