Targeted molecular diversity in drug discovery: integration of structure-based design and combinatorial chemistry

A powerful new approach emerging in drug discovery research combines computational screening of virtual combinatorial libraries against a therapeutic target and targeted combinatorial library synthesis. This new approach includes positive features from both structure-based design and combinatorial chemistry. It has the potential of producing combinatorial libraries with a high hit rate, and hence accelerates the generation of quality lead compounds. The effectiveness of this novel approach has been shown by the design and synthesis of potent inhibitors for serine and aspartyl proteases.