Design and synthesis of benzoic acid derivatives as influenza neuraminidase inhibitors using structure-based drug design

被引：83

作者：

Chand, P ^{[1
]}

Babu, YS ^{[1
]}

Bantia, S ^{[1
]}

Chu, NM ^{[1
]}

Cole, LB ^{[1
]}

Kotian, PL ^{[1
]}

Laver, WG ^{[1
]}

Montgomery, JA ^{[1
]}

Pathak, VP ^{[1
]}

Petty, SL ^{[1
]}

Shrout, DP ^{[1
]}

Walsh, DA ^{[1
]}

Walsh, GW ^{[1
]}

机构：

[1] BIOCRYST PHARMACEUT INC, BIRMINGHAM, AL 35244 USA

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 1997年 / 40卷 / 25期

关键词：

D O I：

10.1021/jm970479e

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

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 ina 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.

引用

页码：4030 / 4052

页数：23

共 55 条

[1] THE NEURAMINIDASE OF INFLUENZA-VIRUS [J].