Utilization of Halogen Bond in Lead Optimization: A Case Study of Rational Design of Potent Phosphodiesterase Type 5 (PDE5) Inhibitors

被引：107

作者：

Xu, Zhijian ^{[1
]}

Liu, Zheng ^{[2
]}

Chen, Tong ^{[1
]}

Chen, TianTian ^{[1
]}

Wang, Zhen ^{[1
]}

Tian, Guanghui ^{[1
]}

Shi, Jing ^{[2
]}

Wang, Xuelan ^{[2
]}

Lu, Yunxiang ^{[3
]}

Yan, Xiuhua ^{[1
]}

Wang, Guan ^{[1
]}

Jiang, Hualiang ^{[1
]}

Chen, Kaixian ^{[1
]}

Wang, Shudong ^{[4
]}

Xu, Yechun ^{[1
]}

Shen, Jingshan ^{[1
]}

Zhu, Weiliang ^{[1
]}

机构：

[1] Chinese Acad Sci, Shanghai Inst Mat Med, State key Lab Drug Res, Shanghai 201203, Peoples R China

[2] Topharman Shanghai Co Ltd, Shanghai 201209, Peoples R China

[3] E China Univ Sci & Technol, Dept Chem, Shanghai 200237, Peoples R China

[4] Univ Nottingham, Sch Pharm, Nottingham NG7 2RD, England

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2011年 / 54卷 / 15期

基金：

上海市自然科学基金;

关键词：

MOLECULES;

D O I：

10.1021/jm200644r

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

For proof-of-concept of halogen bonding in drug design, a series of halogenated compounds were designed based on a lead structure as new inhibitors of phosphodiesterase type S. Bioassay results revealed a good correlation between the measured bioactivity and the calculated halogen bond energy. Our X-ray crystal structures verified the existence of the predicted halogen bonds, demonstrating that the halogen bond is an applicable tool in drug design and should be routinely considered in lead optimization.

引用

页码：5607 / 5611

页数：5

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