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糖原合成酶激酶3β(GSK-3β)是神经退化性疾病如早老性痴呆、II型糖尿病、癌症等多种重复杂性疾病的药物靶标,α-咔啉类化合物具有多种生物活性.以GSK-3β为作用靶点,利用Graebe-Ullmann反应合成了α-咔啉,并采用Buchwald-Hartwig偶联反应合成了9个4位取代的α-咔啉胺类衍生物.体外的GSK-3β激酶酶抑制活性测试表明其中4个化合物具有一定的抑制活性,其中化合物3c的IC50值达到了5.1μmol L-1.同时采用了分子对接方法分别研究了化合物2,3c与大分子蛋白的作用模式,初步探讨了影响抑制活性的原因,为进一步的研究提供了依据.
Glycogen Synthase Kinase 3β (GSK-3β) is a drug target of various degenerative diseases such as Alzheimer’s disease, Type II diabetes, cancer, etc. The α-carbolines have various biological activities. GSK-3βwas used as a target to synthesize α-carboline by Graebe-Ullmann reaction, and 9 4-substituted α-carbamines were synthesized by Buchwald-Hartwig coupling reaction.Grain GSK-3β Kinase inhibition activity test showed that four of the compounds had certain inhibitory activity, and the IC50 value of compound 3c reached 5.1μmol L-1. At the same time, molecular docking method was used to study the mode of action of compound 2,3c and macromolecular protein , Initially discussed the reasons that affect the inhibitory activity, provided the basis for further research.