RECAP - RETROSYNTHETIC COMBINATORIAL ANALYSIS PROCEDURE - A POWERFUL NEW TECHNIQUE FOR IDENTIFYING PRIVILEGED MOLECULAR FRAGMENTS WITH USEFUL APPLICATIONS IN COMBINATORIAL CHEMISTRY

The use of combinatorial chemistry for the generation of new lead mole cules is now a well established strategy in the drug discovery process . Central to the use of combinatorial chemistry is the design and avai lability of high quality building blocks which are likely to afford hi ts from the libraries that they generate. Herein we describe ''RECAP'' (Retrosynthetic Combinatorial Analysis Procedure), a new computationa l technique designed to address this building block issue. RECAP elect ronically fragments molecules based on chemical knowledge. When applie d to databases of biologically active molecules this allows the identi fication of building block fragments rich in biologically recognized e lements and privileged motifs and structures. This allows the design o f building blocks and the synthesis of libraries rich in biological mo tifs. Application of RECAP to the Derwent World Drug Index (WDI) and t he molecular fragments/building blocks that this generates are discuss ed. 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.