title: Synthesis and structure-activity relationship of 5-substituent-2(1H)-pyridone derivatives as anti-fibrosis agents.
abstract: 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 IC(50) of 0.08 mmol/L about 34 times of AKF-PD. The SAR of pyridone derivatives as anti-fibrosis agents was also discussed.
authors.affiliation: Department of Medicinal Chemistry, School of Pharmacy, Central South University, Changsha, Hunan Province, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Chen
authors.forename: Miao-Miao
authors.initials: MM
authors.lastname: Lu
authors.forename: Bin
authors.initials: B
authors.lastname: Liu
authors.forename: Zhuo
authors.initials: Z
authors.lastname: Chen
authors.forename: Qian-Bin
authors.initials: QB
authors.lastname: Li
authors.forename: Li-Jian
authors.initials: LJ
authors.lastname: Tao
authors.forename: Gao-Yun
authors.initials: GY
authors.lastname: Hu
mesh_terms: D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D005355:Fibrosis / Q000188:drug therapy; D006801:Humans; D020128:Inhibitory Concentration 50; D051379:Mice; D041681:NIH 3T3 Cells; D011728:Pyridones / Q000138:chemical synthesis* / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D011728:Pyridones