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

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• 作者：Zhijian Xu ; Zheng Liu ; Tong Chen ; TianTian Chen ; Zhen Wang ; Guanghui Tian ; Jing Shi ; Xuelan Wang ; Yunxiang Lu ; Xiuhua Yan ; Guan Wang ; Hualiang Jiang ; Kaixian Chen ; Shudong Wang ; Yechun Xu ; Jingshan Shen ; Weiliang Zhu
• 刊名：Journal of Medicinal Chemistry
• 出版年：2011
• 出版时间：August 11, 2011
• 年：2011
• 卷：54
• 期：15
• 页码：5607-5611
• 全文大小：789K
• 年卷期：v.54,no.15(August 11, 2011)
• ISSN：1520-4804

文摘

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 5. 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.