title: Utilization of halogen bond in lead optimization: a case study of rational design of potent phosphodiesterase type 5 (PDE5) inhibitors.
abstract: 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.
authors.affiliation: State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Zhijian
authors.initials: Z
authors.lastname: Xu
authors.forename: Zheng
authors.initials: Z
authors.lastname: Liu
authors.forename: Tong
authors.initials: T
authors.lastname: Chen
authors.forename: TianTian
authors.initials: T
authors.lastname: Chen
authors.forename: Zhen
authors.initials: Z
authors.lastname: Wang
authors.forename: Guanghui
authors.initials: G
authors.lastname: Tian
authors.forename: Jing
authors.initials: J
authors.lastname: Shi
authors.forename: Xuelan
authors.initials: X
authors.lastname: Wang
authors.forename: Yunxiang
authors.initials: Y
authors.lastname: Lu
authors.forename: Xiuhua
authors.initials: X
authors.lastname: Yan
authors.forename: Guan
authors.initials: G
authors.lastname: Wang
authors.forename: Hualiang
authors.initials: H
authors.lastname: Jiang
authors.forename: Kaixian
authors.initials: K
authors.lastname: Chen
authors.forename: Shudong
authors.initials: S
authors.lastname: Wang
authors.forename: Yechun
authors.initials: Y
authors.lastname: Xu
authors.forename: Jingshan
authors.initials: J
authors.lastname: Shen
authors.forename: Weiliang
authors.initials: W
authors.lastname: Zhu
mesh_terms: D000818:Animals; D003198:Computer Simulation; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5 / Q000737:chemistry* / Q000378:metabolism; D015195:Drug Design; D006219:Halogens / Q000737:chemistry*; D008958:Models, Molecular; D058986:Phosphodiesterase 5 Inhibitors / Q000138:chemical synthesis*; D011485:Protein Binding; D011817:Rabbits
chemical_list: D006219:Halogens; D058986:Phosphodiesterase 5 Inhibitors; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5