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Solid-Phase Synthesis and Combinatorial Technologies. Pierfausto Seneci Copyright © 2000 John Wiley & Sons, Inc.

ISBNs: 0-471-33195-3 (Hardback); 0-471-22039-6 (Electronic)

9 Applications of Synthetic Libraries

This chapter will try to justify the existence of combinatorial technologies and in particular of small organic molecule libraries, explaining the major impact they have had on the scientific community, especially in the last decade. Both the applications of synthetic libraries and the research fields that have benefited from combinatorial technologies are cited and discussed.

Our analysis naturally starts from pharmaceutical applications, which have been the historical driver of combinatorial technologies and still represent the most relevant field of application for any type of combinatorial library. A brief, but complete, description of the drug discovery process will help in highlighting the areas where combinatorial technologies have had a significant impact, and a few examples will be given to support the utility of synthetic organic libraries for pharmaceutical applications. Related issues that arise during the drug discovery process, such as data management of the chemical and biological information generated and patenting of synthetic libraries and physicochemical or metabolic screens to profile drug candidates from combinatorial libraries, which are often relevant for the whole field of combinatorial technologies, are also covered in this section. The application of combinatorial technologies to similar fields, such as agricultural and veterinary research, will then be briefly mentioned, highlighting the almost complete absence of reports in these fields up to now.

Catalysis is another popular field of application for combinatorial technologies. Discrete libraries of catalysts and ligands, or libraries of combinations of catalysts and ligands, will be described and exemplified. More intriguing encoded pool libraries of catalysts and ligands will be mentioned. Combinatorial optimization both of catalytic protocols and reaction conditions will also be covered. Finally, molecular recognition will be presented. Among others, libraries of synthetic receptors and libraries of coordination complexes are described, together with the adopted screening procedures to determine their activity.

9.1 PHARMACEUTICAL APPLICATIONS

9.1.1 General Considerations

Pharmaceutical research has constantly evolved during the years, and this evolution in turn has brought significant ameliorations to the patient population in curing various diseases. Evolution of the pharmaceutical industry, though, has also led to detrimental consequences for the companies active in this field. The most significant effects are

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