RECAP - Retrosynthetic combinatorial analysis procedure: A powerful new technique for identifying privileged molecular fragments with useful applications in combinatorial chemistry
RECAP - Retrosynthetic combinatorial analysis procedure: A powerful new technique for identifying privileged molecular fragments with useful applications in combinatorial chemistry
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DOI：
10.1021/ci970429i
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发表时间：
1998-05-01
期刊：
影响因子：
--
通讯作者：
Hann, MM
中科院分区：
文献类型：
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作者：
Lewell, XQ;Judd, DB;Hann, MM
现在，组合化学用于生成新的铅分子，现在是药物发现过程中的良好策略。使用组合化学的核心是高质量构建块的设计和可用性，这些块很可能从其产生的图书馆中获得命中。本文中，我们描述了“回顾”（反术组合分析程序），这是一种旨在解决此基础问题的新计算技术。根据化学知识回顾电子碎片分子。当应用于生物活性分子的数据库时，这允许识别富含生物学识别元素以及特权基序和结构的基础片段。这允许设计构建块和富含生物学基序的库的合成。讨论了对Derwent世界药物指数（WDI）的应用以及该产生的分子片段/构建块的应用。我们还描述了WDI片段知识库，我们已经建立了该知识基础，该知识库存储了药物图案，并提及了其在基于结构的药物设计程序中的潜在应用。
The use of combinatorial chemistry for the generation of new lead molecules is now a well established strategy in the drug discovery process. Central to the use of combinatorial chemistry is the design and availability of high quality building blocks which are likely to afford hits from the libraries that they generate. Herein we describe "RECAP" (Retrosynthetic Combinatorial Analysis Procedure), a new computational technique designed to address this building block issue. RECAP electronically fragments molecules based on chemical knowledge. When applied to databases of biologically active molecules this allows the identification of building block fragments rich in biologically recognized elements and privileged motifs and structures. This allows the design of building blocks and the synthesis of libraries rich in biological motifs. Application of RECAP to the Derwent World Drug Index (WDI) and the molecular fragments/building blocks that this generates are discussed. We also describe a WDI fragment knowledge base which we have built which stores the drug motifs and mention its potential application in structure based drug design programs.