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The last ten years has seen an explosion in the exploration and adoption of combinatorial techniques. Indeed, it is difficult to identify any other topic in chemistry that has ever caught the imagination of chemists with such fervor.

For pharmaceutical chemists at least the reason for this change is not hard to fathom. 20 years ago the market for pharmaceuticals was growing at around 10% per annum but more recently the rate of the market growth as decline. At the same time, cost constraints on pharmaceutical research have forced the investigation of methods that offer higher productivity at lower expenses. The belief that combinatorial chemistry will allow the productive and cost-efficient generation of both compounds and drug molecules has fuelled enormous investment in this area.

Solid phase synthesis is highly suited to the synthesis of biopolymers such as DNA, RNA and peptides, as the chemistry required for chain extension is consistent for each step. It was therefore be worthwhile to put considerable effort into the optimization of the coupling conditions to give highly efficient syntheses. However, the history of drug discovery suggests that no single class of compound will provide all the drugs of the future, and thus for combinatorial chemistry to have maximum impact, a large range of bond-forming reaction need to be developed on solid phase.
However, much work remains to be done in this area and this is clearly an area of massive growth for the future.

Combinatorial chemistry represents a broad spectrum of techniques that are rapidly becoming a standard part of the medicinal chemist’s tool kit. But how will this technology develop in the future? Will it become a routine method of lead discovery used by all medicinal chemists or will it remain in the hands of specialists?

Whatever, the degree of integration into the medicinal chemist’s laboratory, one thing is certain. Combinatorial chemistry as a technique for the rapid synthesis of drug-like compounds will continue to make a major impact on the way drug molecules are discovered.

Combinatorial approaches have been introduced from the beginning in the drug discovery field, given their tremendous impact of the identification of new leads. Many active com-pounds have been selected to-date, following combinatorial methodologies, and a considerable number of those have progressed into clinical trials. However, combinatorial chemistry and related technologies for producing and screening large numbers of molecules also find useful applications in other industrial sectors not necessarily related to the pharmaceutical industry. Emerging fields of application of combinatorial technologies are diagnostics, the down-stream processing, catalysis and the new material sectors. 

Many biotechnology/combinatorial-technology companies have been founded in the last few years, with the primary goal to design and produce highly diversified molecular libraries to be screened on selected targets, and the vast majority has definitely caught the attention of pharmaceutical companies. At the same time, rapidly growing sectors of catalyst design and new material design are going to influence chemical industries as well.

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