Potent antiviral activity of novel multi-substituted 4-anilinoquin(az)olines

被引：23

作者：

Saul, Sirle ^{[1
,2
]}

Pu, Szu-Yuan ^{[1
,2
]}

Zuercher, William J. ^{[3
,4
]}

Einav, Shirit ^{[1
,2
]}

Asquith, Christopher R. M. ^{[3
,5
]}

机构：

[1] Stanford Univ, Dept Med, Sch Med, Div Infect Dis & Geog Med, Stanford, CA 94305 USA

[2] Stanford Univ, Dept Microbiol & Immunol, Sch Med, Stanford, CA 94305 USA

[3] Univ N Carolina, Struct Genom Consortium, UNC Eshelman Sch Pharm, Chapel Hill, NC 27599 USA

[4] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA

[5] Univ N Carolina, Dept Pharmacol, Sch Med, Chapel Hill, NC 27599 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2020年 / 30卷 / 16期

基金：

巴西圣保罗研究基金会; 加拿大创新基金会;

关键词：

Dengue Virus; Flavivirus; 4-Anilinoquinoline; 4-Anilinoquinazoline; Antiviral; DENGUE VIRUS; KINASE INHIBITORS; DISCOVERY; OPTIMIZATION; DERIVATIVES;

D O I：

10.1016/j.bmcl.2020.127284

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Screening a series of 4-anilinoquinolines and 4-anilinoquinazolines enabled identification of potent novel inhibitors of dengue virus (DENV). Preparation of focused 4-anilinoquinoline/quinazoline scaffold arrays led to the identification of a series of high potency 6-substituted bromine and iodine derivatives. The most potent compound 6-iodo-4-((3,4,5-trimethoxyphenyl)amino)quinoline-3-carbonitrile (47) inhibited DENV infection with an EC50 = 79 nM. Crucially, these compounds showed very limited toxicity with CC(50 )values > 10 mu M in almost all cases. This new promising series provides an anchor point for further development to optimize compound properties.

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页数：5

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