Unfortunately, compounds that looked promising in vitro didn't always remain so in vivo, often due to bioavailability or toxicity problems. Alone each technology is an intellectual step forward in science, but their synergy has been a major leap for drug development and basic medical research. Pharmaceutical researchers can create and test libraries of thousands, if not millions, of compounds for pharmacological properties relatively quickly. Combinatorial chemistry now plays an important role in polymer chemistry and the development of new pigments, superconducting materials, catalysts, and agrochemicals. This profile will focus on the technologies that contribute to combinatorial chemistry and the development of novel compounds for disease treatment and the probing of biological function.
Automation looms large in the synthesis and screening of immense combinatorial libraries.
New molecules are usually designed by modeling the target-ligand interaction, but may also be fabricated based on a specific set of structural features that impart a desired pharmacophoric property. Then molecular mechanics and dynamics are used to refine the binding interaction. When no structural information on the binding interaction is available, one may draw information from similar, defined binding interactions. These processes yield the structures for compounds that are likely to be the best candidates for drug discovery. The compounds may be analogues of the parent molecule or completely new creations, and will usually be the starting point in combinatorial synthesis.