摘要
在现有IRAK4抑制剂MK-32和AU-5的基础上,利用开环策略和拼合原理,结合分子对接技术,设计并合成了12个以吡啶为基本母核的目标化合物。采用放射性同位素标记法评价了目标化合物对IRAK4激酶的抑制活性。结果表明,该类化合物对IRAK4显现出良好的抑制活性。其中5个化合物的IC50小于1μmol/L,值得进一步研究。
Based on the known IRAK4 inhibitors MK-32 and AU-5,we designed and synthesized 12 pyridine-based target compounds by adopting open-ring and hybrid strategies,and combining molecular docking technology.The bioassays determined by radioisotope labeling demonstrated that the target compounds displayed good inhibitory activity against IRAK4.Among them,the IC50 value of 5 compounds was less than 1 μmol/L,suggesting that these compounds may be candidates for further investigation.
出处
《中国药科大学学报》
CAS
CSCD
北大核心
2017年第6期670-674,共5页
Journal of China Pharmaceutical University
基金
国家自然科学基金资助项目(No.21472244)~~
