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

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

卷:30

Article

Saul, Sirle^1,2  Pu, Szu-Yuan^1,2  Zuercher, William J.^3,4  Einav, Shirit^1,2  Asquith, Christopher R. M.^3,5 

[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

关键词: Dengue Virus;    Flavivirus;    4-Anilinoquinoline;    4-Anilinoquinazoline;    Antiviral;   

DOI  :  10.1016/j.bmcl.2020.127284

来源: Elsevier

【 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.

【 授权许可】

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