Macrocycles in Drug Discovery

This book will review macrocycles in drug discovery, both those of natural origin and semi-synthetic derivatives of natural products, and those designed and synthesized based on principles of medicinal chemistry. A variety of macrocyclic natural products have become important drugs or have been identified as leads to marketed drugs. This text will discuss these compounds in the context of their broad chemotype as compounds composed of large rings. The medicinal chemistry of natural products is interesting in itself, but lessons learned from these compounds, in terms of the relationship between structure and desirable physicochemical properties, is now informing the design of fully synthetic drug candidates against a variety of targets. Furthermore, as more and more non-classical drug targets, such as protein-protein interactions, are pursued in the pharmaceutical industry, macrocyclic molecules are becoming increasingly important as they offer a way to provide drug-protein interactions that cover a larger surface area than traditional small molecules. An indication of this growing importance is the fact that several companies now provide libraries of macrocyclic molecules produced by proprietary chemical technology to use for lead generation. Providing a wide reaching review of this important area in a single volume, this book will be of interest to biochemists, pharmaceutical scientists and medicinal chemists working in industry or academia.