金刚烷胺衍生物的设计、合成及其抗禽流感病毒活性

Design,synthesis and anti-H5N1 activities of amantadine derivatives

目的设计合成金刚烷胺衍生物并对其进行抗禽流感病毒活性测试。方法以金刚烷甲酰氯和氨基酸甲酯盐酸盐为起始原料,经酰胺化、水解、成盐等反应依次得到3个系列金刚烷胺衍生物。以金刚烷胺为阳性对照,采用幼犬肾(MDCK)细胞系噬斑形成实验测定目标化合物的抗禽流感病毒活性。结果与结论共合成了20个未见报道的新化合物,目标化合物的结构均经1H-NMRI、R、MS谱确证;仅有化合物A5显示出较好的抗禽流感病毒活性。

Based on the good antiviral activity of lead compound amantadine,in order to study on the influence of the different groups on adamantane scaffold on the anti-H5N1 activity,twenty novel amantadine derivatives were designed and synthesized.The synthetic routes of the target compounds were as follows：series A（A1-A10） were obtained from 1-adamantanecarbonyl chloride by reaction with amino acid methyl ester hydrochloride;series B（B1-B5） were obtained from amantadine derivatives series A by acid-hydrolysis;series C（C1-C5） were synthesized from series B treated with NaOH.The structure of target compounds were identified by IR,1H-NMR,13C-NMR and MS.Anti-H5N1 activities of these novel compounds were tested by plaque assays（MTT） with amantadine as the positive control.Only compound A5 showed potent anti-H5N1 activities（EC50=6.67 mg·L-1）.