Chand P, Babu Y S, Bantia S, Chu N, Cole L B, Kotian P L, Laver W G, Montgomery J A, Pathak V P, Petty S L, Shrout D P, Walsh D A, Walsh G M
BioCryst Pharmaceuticals, Inc., Birmingham, Alabama 35244, USA.
J Med Chem. 1997 Dec 5;40(25):4030-52. doi: 10.1021/jm970479e.
A series of 94 benzoic acid derivatives was synthesized and tested for its ability to inhibit influenza neuraminidase. The enzyme-inhibitor complex structure was determined by X-ray crystallographic analysis for compounds which inhibited the enzyme. The most potent compound tested in vitro, 5 (4-acetylamino)-3-guanidinobenzoic acid), had an IC50 = 2.5 x 10(-6) M against N9 neuraminidase. Compound 5 was oriented in the active site of the neuraminidase in a manner that was not predicted from the reported active site binding of GANA (4) with neuraminidase. In a mouse model of influenza, 5 did not protect the mice from weight loss due to the influenza virus when dosed intranasally.
合成了一系列94种苯甲酸衍生物，并测试了它们抑制流感神经氨酸酶的能力。通过X射线晶体学分析确定了抑制该酶的化合物的酶-抑制剂复合物结构。体外测试的最有效化合物5（4-乙酰氨基）-3-胍基苯甲酸对N9神经氨酸酶的IC50 = 2.5×10（-6）M。化合物5在神经氨酸酶的活性位点中的取向方式与报道的GANA（4）与神经氨酸酶的活性位点结合情况预测的不同。在流感小鼠模型中，经鼻给药时，化合物5不能保护小鼠免于因流感病毒导致的体重减轻。
