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.

引用

页码：359 / 362

页数：4

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