论文部分内容阅读
目的寻找新型的非ATP竞争糖原合成酶激酶-3β(GSK-3β)抑制剂。方法针对GSK-3β的非ATP结合的底物作用位点为靶点,采用Autodock程序对类药性小分子库Maybridge进行虚拟筛选寻找新型GSK-3β抑制剂。采用克脑文格尔反应,环合及N-烷基化反应制备目标化合物。采用体外酶抑制活性测试目标化合物的活性。结果化合物2-(2-呋喃基)-5-苄基-2,3-二氢苯并[b][1,4]硫氮杂-4(5H)-酮对GSK-3β具有中等抑制活性(IC5047.69±2.38μmol.L 1)。结论活性化合物的结构与目前报道的其他GSK-3β抑制剂不同,可望作为新的先导化合物,值得进一步研究。
Aim To find a new non-ATP competitive glycogen synthase kinase-3β (GSK-3β) inhibitor. Methods Targeted at the non-ATP binding substrate site of GSK-3β, the Autodock program was used to screen novel MDR-like Maybank for novel GSK-3β inhibitors. The target compounds were prepared by the reaction of Brackinger-Wacker reaction, cyclization and N-alkylation. The activity of the target compound was tested using in vitro enzyme inhibition activity. Results The compound 2- (2-furyl) -5-benzyl-2,3-dihydrobenzo [b] [1,4] thiazepin-4 (5H) -one has moderate inhibitory activity against GSK-3β (IC 5047.69 ± 2.38 μmol.L 1). Conclusion The structure of the active compound is different from other GSK-3β inhibitors reported so far. It is expected to be a new lead compound for further study.