ABSTRACT
Combinatorial chemistry has evolved greatly since its conception by Merrifield in 1963 where the first solid-phase synthesis of peptides was reported.1 For the next 30 years, the primary use of solidphase chemistry remained dedicated to peptide synthesis, although there were some efforts dedicated to the development of functionalized resins for their use in solution-phase synthesis. However, it was not until the early 1990s that combinatorial chemistry moved into the area of small molecule synthesis when the first publication of a solid-phase combinatorial synthesis of benzodiazepines appeared.2 Industry immediately noticed this breakthrough, embraced it, and began investing more resources into the development of combinatorial chemistry to expedite the drug discovery process. As a result, from the mid-1990s to the end of the last decade, an explosion of reports appeared in the literature where traditional solution-phase methodologies were ported and/or adapted to solid-phase combinatorial chemistry.
