Current directions in the evolution of compound libraries.

Synthetic compound libraries have been available for over a century, but in the last 15 years they have become increasing important in early-stage drug discovery projects. The qualities that these libraries possess impart a dramatic effect on hit discovery, on the subsequent steps of hit-to-lead progression, and on lead optimization by medicinal chemists. More recently, synthetic libraries have found an important application in chemical genetics. Concurrently, ideas have evolved regarding the application of the different types of synthetic approaches that are variously described as combinatorial chemistry, high-throughput synthesis, or diversity-oriented synthesis. This review will discuss current directions of synthetic chemistry, natural product chemistry and chemoinformatics, which relate to the various types of compound libraries that are in use in drug discovery and chemical genetics.