合理设计一些容量小的、针对特定靶标的化合物库 (称为集中库 ,focused library) ,是当前组合库设计中的热点。当靶标的三维结构可以通过 X射线衍射或 NMR等手段确定后 ,人们就能采用几种不同的策略来进行组合库的设计。本文讨论了在靶标结合位点的约束下 ,进行组合库设计的主要方法及程序 ,同时强调了它们的优点与不足。通过这些方法的成功应用实例 ,显示了它们在新药创制中的广泛应用前景 It is a hot spot in the design of the current combinatorial library to reasonably design some small-capacity compound libraries for specific targets (called focused libraries). When the three-dimensional structure of the target can be determined by means of X-ray diffraction or NMR, etc., one can adopt several different strategies to design the combinatorial library. This article discusses the main methods and procedures for combinatorial library design under the constraints of target binding sites, highlighting their strengths and weaknesses. The successful application of these methods shows their broad application prospects in the creation of new drugs