State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.
J Med Chem. 2011 Aug 11;54(15):5607-11. doi: 10.1021/jm200644r. Epub 2011 Jul 14.
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.
为了在药物设计中证明卤键的概念验证，我们基于一个先导结构设计了一系列卤代化合物，作为磷酸二酯酶 5 的新型抑制剂。生物测定结果表明，所测生物活性与计算得到的卤键能之间具有良好的相关性。我们的 X 射线晶体结构证实了预测的卤键的存在，证明卤键是药物设计中一种可行的工具，在先导化合物优化中应常规考虑。
