文献类型：期刊文献

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

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

年份：2011

卷号：54

期号：15

起止页码：5607

外文期刊名：JOURNAL OF MEDICINAL CHEMISTRY

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000293419400032)】；

基金：This work was supported by NNSF (Grant 20721003), CAS (Grants KSCX2-YW-R-168 and KSCX2-YW-R-208), the "100 Talents Project" of CAS (to Y.X.), Shanghai S&T Foundation (Grant 09540703900), National Science & Technology Major Project (Grants 2009ZX09301-001 and 2009ZX09102-056), International Cooperation Project of MOST (Grant 2010DFB73280), the State Key Laboratory of Drug Research (Grant SIMM1106KF-05), and Natural Science Foundation of Shanghai (Grant 11ZR1408700). The authors thank Dr. Nick K. Terrett at Ensemble Therapeutics for his review of the manuscript.

语种：英文

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.