4-(1＇-哌嗪基)喹啉化合物的合成与分子动力学模拟研究

Synthesis and Molecular Dynamics Simulation of 4-( piperazin-1-yl) Quinolines

分别以7-氟-4-氯喹啉(化合物1)及7-甲氧基-4-氯喹啉(化合物2)为原料合成7-氟-4-(1'-哌嗪基)喹啉(化合物3)和7-甲氧基-4-(1'-哌嗪基)喹啉(化合物4),化合物结构以ESI-MS确证.将化合物3和化合物4分别与HER1、HER2蛋白形成的复合物进行分子动力学模拟,结果显示:化合物3与HER1的亲和力和化合物4与HER1的亲和力相似;化合物4与HER2的亲和力大于化合物3与HER2的亲和力;目标化合物与蛋白氨基酸残基形成氢键不是亲和力大小的决定性因素.

7-fluoro-4-（ piperazin-1-yl） quinolone 3 and 7-methoxy-4-（ piperazin-1-yl） quinoline 4 were synthesized from 7-fluoro-4-chloroquinoline 1 and 7-methoxy-4-chloroquinoline 2, respectively and their structures were confirmed by ESI-MS. The molecular dynamics simulation of complex of 3 or 4 with HER1 and HER2 protein were performed. The main results showed that the binding affinity of 3 to HER1 was similar to that of 4 to HER1; the binding affinity of 4 to HER2 was stronger than that of 3 to HER2.The hydrogen bonds were not a decisive factor for affinity.