Synthesis and structure-activity relationship of 5-substituent-2(1H)-pyridone derivatives as anti-fibrosis agents

Pyridone compounds, such as pirfenidone (PFD) and fluorofenidone (AKF-PD), are multi-target anti-fibrotic agents. Using PFD and AKF-PD as the leading compounds, two series of novel (5-substituent)-2(1H)-pyridone compounds were synthesized with the purpose of maintaining multi-targeting property and overcoming the drawbacks of fast metabolism. These derivatives demonstrated good proliferation inhibiting activity against NIH3T3 cells by MTT assay with AKF-PD as the positive control. Compound 5b exhibited a high potent of anti-fibrosis with a IC50 of 0.08 mmol/L about 34 times of AKF-PD. The SAR of pyridone derivatives as anti-fibrosis agents was also discussed. (C) 2012 Elsevier Ltd. All rights reserved.