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 fervour.
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 bee worthwhile
to put considerable effort into the optimisation 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.
