Abstract

In the process of finding new drug candidates medicinal chemists nowadays have a variety of options to choose from, one is to apply combinatorial chemistry techniques. Since the early 1990s synthetic and analytical methods as well as new technologies have been growing repidly in the area of combinatorial chemistry. Applying these techniques have resulted in the production of large numbers of compounds. A trend is observed towards smaller libraries of compounds with more drug-like properties. An analysis is made to establish the contribution of combinatorial chemistry in providing new lead candidates for (pre)clinical development towards new pharmaceutical products. Ten representative examples are given to describe the impact of ombinatorial chemistry on different levels of the lead discovery and optimization process. Furthermore, reports on combinatorial chemistry products that are already in (pre)clinical development were traced back to their source. The interim analysis showed only limied su ccess of combinatorial chemistry approaches in terms of delivering leads. Second generation libraries appear more drug-like and focused and may result in more compounds entering clinical studies in the future

Keywords: Combinatorial Chemistry, Interim Analysis, Thymidylate syntheses Inhibitors, Solid-Phase, Dansyltyrosine derivatives, Potassium channel blockers, Phenylstilbene library, Protein tyrosine kinases, Benzodiazepines, Src tyrosine