Introduction

The introduction of a new pharmaceutical is a lengthy and expensive undertaking. Methods which promise to shorten the time or the cost are eagerly taken up, and this is clearly the case with combinatorial chemistry and multiple parallel synthesis.

Combinatorial chemistry is somewhat hard to define precisely, but generally speaking, it is a collection of methods that allow the simultaneous chemical synthesis of large numbers of compounds using a variety of starting materials. The resulting compound library can contain all of the possible chemical structures that can be produced in this manner. Multiple parallel synthesis is a related group of methodologies used to prepare a selected smaller subset of the molecules that could in theory have been prepared. The content of libraries prepared by multiple parallel synthesis is more focused and less diverse than those constructed with combinatorial technology.

The primary benefit that combinatorial and multiple parallel chemistry bring to drug synthesis is speed. As with most other human endeavors, uncontrolled speed may be exhilarating but is not particularly useful. Rapid construction of compounds that have no chance of becoming drugs is of little value to the medicinal chemist. After an initial euphoric period when many investigators thought that any novel compound had a realistic chance of becoming a drug, realism has now returned, and libraries are being constructed that reflect the accumulated wisdom of the field of medicinal chemistry. Combina-methods have permeated and irreversibly altered most phases of drug seeking that benefits from the attention of chemists. The successful contemporary medicinal chemist must be aware of the strengths and weaknesses of these exciting new methods and be able to apply them cunningly. In the proper hands combining medicinal chemical insight with enhanced speed of synthesis is very powerful.

Libraries are constructed both in solution and on solid supports and the choice between

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