新型吡啶-2-酮酰胺类化合物的设计、合成及抗乙肝病毒活性研究

Design,synthesis and anti-HBV activity of novel 2-prindyl ketone derivatives

目的设计合成吡啶-2-酮酰胺类新型化合物并对其进行抗病毒活性研究。方法以药效团模型为指导,经Heck反应、选择性硝化反应、催化氢化反应、酰化反应以及开环重排反应等设计合成目标化合物。所合成化合物经1H NMR谱图进行确证,并对其进行抗HBV-DNA复制活性筛选。结果设计合成的新型-2-吡啶酮酰胺类化合物对HBV-DNA复制都有一定的抑制活性,其中化合物6h、6e和6a抑制活性最好,值得进一步关注。结论吡啶环N原子上接有对乙氧基苯基时抑制HBV-DNA活性最好,为活性必须基团。

Objective To design and synthesize the new 2-pyridyl ketone amide derivatives and test the antiviral activity. Methods According to the pharmacophore model, a new class of 2-pyridyl ketone amide derivatives was designed, which were synthe- sized by Heek reaction, selective nitration reaction, catalytic hydrogenation reaction, acylafion reaction and the open-loop rearrange- ment reaction. All the synthesized compounds were confirmed by ~ H NMR, and their anti-HBV-DNA replication activity were deter- mined. Results The designed novel 2-pyridyl ketone amide derivatives had inhibitory activity against HBV-DNA replication. Among them, compounds 6h,6e and 6a showed the best inhibitory activity. Conclusion When the 4-ethoxyl phenyl group was attached on the N atom of the benzyl ring, the compounds revealed good inhibitory activity.