Combinatorial chemistry: A rational approach to chemical diversity

Although knowledge-based de novo design of high affinity ligands for receptors or enzymes appears to be the most rational approach to the discovery of new pharmacologically active substances, high throughput random screening of compounds with no known structural similarity to the natural ligand has proved to be a highly efficient method. In order to :increase the number of new molecules, methods of combinatorial synthesis have been considerably developed in recent years. In this review we will examine some of the main strategies for generating large arrays of diverse molecular entitles, the screening of such libraries, the methods used to identify an active compound, and the chemical technologies used in the development of this very promising source of new drugs.