Structure-Activity Relationship Study of QL47: A Broad-Spectrum Antiviral Agent

被引：17
|
作者：
Liang, Yanke [1 ,2 ]
de Wispelaere, Melissanne [3 ]
Carocci, Margot [3 ]
Liu, Qingsong [1 ,2 ]
Wang, Jinhua [1 ,2 ]
Yang, Priscilla L. [3 ]
Gray, Nathanael S. [1 ,2 ]
机构：
[1] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02215 USA
[2] Harvard Med Sch, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA
[3] Harvard Med Sch, Dept Microbiol & Immunobiol, Boston, MA 02115 USA
来源：
ACS MEDICINAL CHEMISTRY LETTERS | 2017年 / 8卷 / 03期
关键词：
Dengue virus; broad-spectrum antiviral; QL47; structure-activity relationship; KINASE INHIBITORS; DENGUE VIRUS; B-CELL; PROTEASE INHIBITORS; DISCOVERY; CANCER; MTOR; REPLICATION; FLAVIVIRUS; INFECTION;
D O I：
10.1021/acsmedchemlett.7b00008
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
Here we report the structure activity relationship (SAR) investigations of QL-XII-47 (QL47), a compound that possesses broad-spectrum antiviral activity against dengue virus and other RNA viruses. A medicinal chemistry campaign initiated from QL47, a previously reported covalent BTK inhibitor, to derive YKL-04-085, which is devoid of any kinase activity when screened against a panel of 468 kinases and with improved pharmacokinetic properties. Both QL47 and YKL-04-085 are potent inhibitors of viral translation and exhibit cellular antiviral activity at 35-fold lower concentrations relative to inhibition of host-cell proliferation.
引用
收藏
页码：344 / 349
页数：6
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