4-N-苯胺基喹啉衍生物的合成及胆碱酯酶抑制活性

Syntheses and Anti-cholinesterase Activity of 4-N-Phenylaminoquinoline Derivatives

设计合成了一系列4-N-苯胺基喹啉类衍生物,采用Ellman法测定了目标化合物对乙酰胆碱酯酶(AChE)和丁酰胆碱酯酶(BChE)的抑制活性.结果表明,当喹啉环上连有伸长的吡啶季铵盐片段时,可显著提高目标化合物的胆碱酯酶抑制作用.化合物16对AChE和BChE具有明显的双重抑制作用,其IC_(50)值分别为0.92和14.20μmol/L,抑制效果强于阳性对照药加兰他敏.

A series of 4-N-Phenylaminoquinoline derivatives was designed and synthesized, and their anti-cholinesterase activities were evaluated using Ellman assay. The results demonstrated that the stretched-out quaternary pyridine in quinoline ring greatly improved the cholinesterase inhibition of target compounds. Compound 16 exhibited the most potent inhibitory activities against both acetylcholinesterase（AChE） and bu- tyrylcholinesterase（BChE） from the prepared series, with IC50 values of 0. 92 and 14. 20 μmol/L, respective- ly, which showed superior activitities compared with the reference drug galanthamine. These results suggest that compound 16 may be valuable as a new parent compound for further structural modifications.