ABSTRACT
This chapter describes a practical integration of structure-based design and combinatorial chemistry aimed at enhancing the effectiveness of both approaches. New approaches to drug discovery that are able to integrate many different types of information are needed to seize this opportunity and drive an optimally efficient discovery process. The limitations and strengths of structure-based design and combinatorial chemistry approaches are complementary. Combinatorial chemical approaches can potentially produce millions of compounds, more than are desired or useful, which tax target-screening efforts and compound tracking. As with structure-based design approaches, the process is an iterative one in which structure-activity relationship data and structural data guide not only the iterative selection of library members for testing, but also the design of later generation library scaffolds. Structure-based drug design has become a highly developed technology that is in active use in most major pharmaceutical companies.
