抗流感病毒抑制剂Nucleozin衍生物的设计、合成及抗病毒活性评价

Synthesis and Antiviral Activity Evaluation of Derivatives of Anti-influenza Virus Inhibitor Nucleozin

小分子化合物Nucleozin作为靶向流感病毒核蛋白的抑制剂具有良好的抑制活性。本文围绕Nucleozin分子中与哌嗪环直接相连的芳环部分进行研究。通过钯催化偶联反应合成了一系列Nucleozin衍生物,通过检测所合成化合物对流感病毒H1N1的抑制活性,明确了Nucleozin分子中该部分的构效关系。利用甲基在药物分子设计中的作用,设计将分子中的氯原子替换为甲基,发现与原型分子Nucleozin相比其抑制活性有了明显的提高。本文的结果对该类分子成药性的提高具有积极意义。

Nucleozin has good inhibitory activity as an inhibitor against influenza virus nucleoprotein. In this paper,we investigate the aromatic ring part which is connected directly with piperazine in the nucleozin molecular structure. A series of nucleozin derivatives were synthesized by palladium catalyzed coupling reaction,and the structure-activity relationship of this part in nucleozin molecule was clarified by detecting the inhibitory activities of the synthesized compounds on influenza virus H1 N1. After replacing the chlorine atom in the molecule with a methyl group,it was found that the inhibitory activity is significantly improved compared with the prototype molecule nucleozin. This study has a significant meaning in the drug-like improvement of this kind of molecular.