5-氨甲基咔唑衍生物的设计、合成及抗阿尔茨海默病活性

以5-氨甲基咔唑为先导物，在其母环及5-位氨甲基的氮原子上引入不同的取代基，设计、合成了一系列咔唑衍生物，测试了其乙酰胆碱酯酶(AChE)和丁酰胆碱酯酶(BChE)抑制活性，以及体外神经元细胞保护活性，并总结了构效关系。其中，化合物8a具有AChE/BChE双重抑制活性，同时还能够有效保护PC12细胞免受Aβ造成的损伤，展现出良好的开发前景。
A series of carbazole derivatives were designed and synthesized via the introduction of various substituents on the carbazole template and the nitrogen atom using 5-aminomethyl substituted carbazole as the lead compound. The inhibitory activity towards AChE/BChE and the neuroprotective effect against Aβ-induced toxicity were evaluated by Ellman and MTT assay, respectively. Furthermore, the SAR of the target compounds was discussed. Among all the target compounds, compound 8a showed dual inhibitory activity toward both AChE and BChE, and could effectively protect PC12 cells from Aβ-induced toxicity, indicating compound 8a could be considered as a promising candidate against Alzheimer′s disease