Integration of combinatorial chemistry and structure-based drug design.
During the past 15 years, the focus of the drug design community has undergone considerable change. After decades dedicated to studying traditional folk medicine and the biological activity of natural compounds as the major source of drugs, the growing pathobiological, mechanistic, physicochemical and structural knowledge base, combined with the advent of computers, has led to the possibility of rational drug design. Pharmaceutical research is a difficult and time-consuming process and while the first benefits of rational approaches have begun to reach mature stages of development, the next paradigm shift, introducing high-throughput screening (HTS) and combinatorial chemistry (CC) techniques, is already upon us. It has, however, taken only a few years for the realization that vast numbers of compounds, either through the screening of combinatorial libraries of mixtures or collections of single compounds, could not meet the advanced expectations for dramatically improved pharmaceutical research production. More often, researchers now strive for a balanced strategy between unguided HTS and the supervised design of compound libraries of single compounds.
Antel
J
J
CADD, PH-FDC, Solvay Pharmaceuticals GmbH, Hans-Böckler Allee 20, D-30173 Hannover, Germany. Jochen.Antel@Solvay.com