Discovery of Imidazopyridine Derivatives as Highly Potent Respiratory Syncytial Virus Fusion Inhibitors

被引：71
作者：
Feng, Song [1 ]
Hong, Di [1 ]
Wang, Baoxia [1 ]
Zheng, Xiufang [1 ]
Miao, Kun [1 ]
Wang, Lisha [2 ]
Yun, Hongying [1 ]
Gao, Lu [3 ]
Zhao, Shuhai [1 ]
Shen, Hong C. [1 ]
机构：
[1] Roche Innovat Ctr Shanghai, Med Chem, Shanghai 201203, Peoples R China
[2] Roche Innovat Ctr Shanghai, Mol Design & Chem Biol, Shanghai 201203, Peoples R China
[3] Roche Innovat Ctr Shanghai, Infect Dis Pharmaceut Res & Early Dev, Shanghai 201203, Peoples R China
来源：
ACS MEDICINAL CHEMISTRY LETTERS | 2015年 / 6卷 / 03期
关键词：
Respiratory syncytial virus (RSV); virus; antiviral; fusion inhibitors; imidazopyridine; heterocycle; OPTIMIZATION; INFLUENZA; ENTRY;
D O I：
10.1021/acsmedchemlett.5b00008
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
A series of imidazolepyridine derivatives were designed and synthesized according to the established docking studies. The imidazopyridine derivatives were found to have good potency and physical-chemical properties. Several highly potent compounds such as 8ji, 8j1, and 8jm were identified with single nanomolar activities. The most potent compound 8jrn showed an IC50 of 3 nM, lower nnicrosome clearance and no CYP inhibition. The profile of 8jrn appeared to be superior to BMS433771, and supported further optimization.
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收藏
页码：359 / 362
页数：4
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