Recent advances in the generation of chemical diversity libraries

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Abstract
In recent years, screening in combination with a diverse compound collection has become a powerful method for discovering leads for the ever‐increasing number of new biologically active peptides, proteins, receptors, and enzymes discovered continually. As a result, the rapid generation and screening of compound libraries (collections) have recently become important major tools in the search for novel lead structures. Diverse collections of compounds have been acquired by many strategies; these include (1) natural products from plants, fermentation, marine organisms, insect toxins, and ethnic pharmacotherapies; (2) recombinant randomized peptide libraries (often referred to as biological diversity); (3) multiple peptide synthesis; and (4) non‐peptidic synthetic libraries. The present review provides an overview of the recent advances in the field of peptide and non‐peptidic synthetic libraries. The progress made thus far is broadly divided into two categories: (1) Amide based libraries. These libraries share the concepts of the peptide library strategies; much of the referenced work thus refers to peptides, reflecting the bias of the literature to date. (2) Non‐amide based libraries. This promising technology combines solid phase synthesis with classical organic synthesis to provide large numbers of compounds with desirable bioavailability and pharmacokinetics for screening. The basic premise behind the second approach is that the high affinity ligands, when identified, will be much more likely to become useful therapeutic agents than the compounds discovered from amide based libraries. Synthesizing small heterocyclic ring systems that use ligands of diverse biological activity via combinatorial strategies is a fast developing branch of medicinal chemistry. We are at an early state in the development of combinatorial chemistry. However, this dramatic convergence of technologies represents a fundamental advance in medicinal chemistry and promises to play a major role in future drug discovery efforts. © 1994 Wiley‐Less, Inc.