吡啶类IRAK4抑制剂的设计、合成及生物活性评价

Design, synthesis and biological evaluation of pyridine-based IRAK4 inhibitors

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1 μmol/L，值得进一步研究。

Abstract: 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.