新型苯甲酸衍生物类流感病毒神经氨酸酶抑制剂的合成及初步活性评价

Synthesis and preliminary activity evaluation of benzoic acid derivatives as the influenza virus neuraminidase inhibitors

摘要:

以4-氨基-3-碘苯甲酸甲酯为原料，经过一系列反应得到苯甲酸衍生物类流感病毒神经氨酸酶抑制剂I-IV，并经化合物II衍生得到化合物V-VII，结构经1HNMR,13CNMR,MS确证；用化学荧光法测定抑制率，测试选用流感病毒菌株H3N2（California/04），H1N1（California/99）和B（Shanghai/02），结果显示：在I-IV中，苯环C3位置侧链越大，化合物的活性越低；V-VII中，在苯环侧链α位的碳上引入羟基后比在β位碳上单羟基的化合物活性增强，这表明α位的碳上电子环境的变化对活性有较大影响；在苯环侧链α位的碳上含有单羟基的化合物VII具有对A型流感病毒最强的活性。

Abstract:

A kind of kind of benzoic acid derivatives influenza neuraminidase inhibitors I to IV were prepared from the starting materials of 4-amino-3-iodine benzoic acid through a series of reactions , the compounds V - VII derivatived from compound II , and the structures were characterized by 1H NMR,13C NMR and MS.Inhibition rate determined by chemical fluorescence, and the activity test was performed by the influenza virus strains H3N2 (California / 04), H1N1 (California / 99) and B (Shanghai / 02), the results showed: Among the compounds I - IV, the greater side chain at C3 position,the lower activity of compounds; Among the compounds V - VII, introduction of hydroxyl on the α carbon in the side chains of benzene ring, the inhibitory activity stronger than single hydroxyl on β carbon, which suggested that the change of electronic environment on the α carbon had a greater influence on activity; Compound VIIcontaining single hydroxyl at α carbon in side chains of benzene ring possessed the strongest activity of type A influenza virus.