中国药科大学学报2024，Vol.55Issue(1)：73-86,14.DOI:10.11665/j.issn.1000-5048.2024010201
BTK/JAK3双靶点抑制剂的设计合成和生物活性评价
Design,synthesis and biological study of BTK/JAK3 dual-target inhibitors
岑丽芳 1程铭 1任玮杰 1叶柳 1王禄华 1郭维博 2张强 3徐云根1
作者信息
- 1. 中国药科大学药物化学系, 南京 210009
- 2. 中国药科大学药物化学系, 南京 210009||西安新通药物研究股份有限公司, 西安 710077
- 3. 西安新通药物研究股份有限公司, 西安 710077
- 折叠
摘要
Abstract
In the present study,the compound XL-12 from our previous work was utilized as a lead compound.Through the optimization of the terminal phenyl ring,12 target compounds were designed and synthesized.The structures of all target compounds were confirmed by 1H NMR,13C NMR,and H RMS.In vitro enzyme activity assay showed that most compounds demonstrated significant inhibitory activity toward Bruton's tyrosine kinase(BTK)and Janus kinase 3(JAK3).Among them,compound I-3 exhibited moderate cell proliferation inhibitory activity toward Daudi cells and BaF3-JAK3 cells.In the evaluation of anti-inflammatory activity in vitro,compound I-3 could effectively inhibit the production of inflammatory factors IL-6;besides,it exhibited superior anti-inflammatory activity compared to ibrutinib in xylene-induced ear swelling model in mice.关键词
类风湿性关节炎/BTK抑制剂/JAK3抑制剂/双靶点抑制剂/抗炎Key words
rheumatoid arthritis/BTK inhibitor/JAK3 inhibitor/dual-target inhibitors/anti-inflammatory分类
医药卫生引用本文复制引用
岑丽芳,程铭,任玮杰,叶柳,王禄华,郭维博,张强,徐云根..BTK/JAK3双靶点抑制剂的设计合成和生物活性评价[J].中国药科大学学报,2024,55(1):73-86,14.
