TARGETED MOLECULAR DIVERSITY IN DRUG DISCOVERY - INTEGRATION OF STRUCTURE-BASED DESIGN AND COMBINATORIAL CHEMISTRY

A powerful new approach emerging in drug discovery research combines c omputational screening of virtual combinatorial libraries against a th erapeutic target and targeted combinatorial library synthesis. This ne w approach includes positive features from both structure-based design and combinatorial chemistry. It has the potential of producing combin atorial libraries with a high hit rate, and hence accelerates the gene ration of quality lead compounds. The effectiveness of this novel appr oach has been shown by the design and synthesis of potent inhibitors f or serine and aspartyl proteases.