Over the last two decades we have seen a dramatic change in the drug discovery process brought about by chemical library technologies and high-throughput screening, along with other equally remarkable advances in biomedical research. Though still evolving, chemical library technologies have become an integral part of the core drug discovery technologies. This volume primarily focuses on the design aspects of the chemical library technologies. Library design is a process of selecting useful compounds from a potentially very large pool of synthesizable candidates. For drug discovery, the selected compounds have to be biologically relevant. Given the enormous number of compounds accessible to the contemporary synthesis and purification technologies, powerful tools are indispensible for uncovering those few useful ones. This book includes chapters on historical overviews, state-of-the-art methodologies, practical software tools, and successful application of chemical library design written by the best expert practitioners.
The book is divided into five section. Section I covers general topics. Chapter 1 highlights the key events in the history of high-throughput chemistry and offers a historical perspective on the design of screening, targeted, and optimization libraries. Chapter 2 is a short introduction to the basics of chemoinformatics necessary for library design. Chapter 3 describes a practical algorithm for multiobjective library design. Chapter 4 discusses a scalable approach to designing lead generation libraries that emphasize both diversity and representativeness along with other objectives. Chapter 5 explains how Free–Wilson selectivity analysis can be used to aid combinatorial library design. Chapter 6 shows how predictive QSAR and shape pharmacophore models can be successfully applied to targeted library design. Chapter 7 describes a combinatorial library design method based on reagent pharmacophore fingerprints to achieve optimal coverage of pharmacophoric features for a given scaffold.