Combinatorial Chemistry

Combinatorial chemistry has turned traditional chemistry upside down when introducing automated substance synthesis to the drug discovery process. By accelerating the process of chemical synthesis, it allows rapid synthesis of large, organized collections of compounds.

The automated synthesis of molecules fills our stocks of substances

Whenever Bayer's scientists search for new drug candidates, they start looking in our in-house compound library – with its more than four million molecules. By synthesizing new substances, chemists ensure that this collection is always growing. Their work has been revolutionized by the automated processes of combinatorial chemistry, which became a feature of medical chemistry around the turn of the millennium.


Up until then, chemists had only been able to produce one precisely defined substance per unit of time using classical methods of synthesis. These methods were able to generate a maximum of 150-200 compounds a year. Robotic systems, which today perform such syntheses in parallel, can increase this number many times over.


The compound’s basic structure is selectively varied


Automated synthesis is based on the concept of combinatorial chemistry. Starting with a parent molecule – a lead compound or lead – variants are systematically created according to a chemist's specifications by attaching various chemical groups to the basic structure. The result is a number of similar substances which differ from each other only in terms of the additional side groups (see chart). In biological assays, the researchers subsequently examine which molecular variants are best at producing the desired effect. This provides information on the relations between molecular structure and effect, giving the chemists important clues for further optimization. With the help of combinatorial chemistry, a modern laboratory can synthesize and further enhance a large number of new compounds– and add them to our stock of substances – in an automated process. Once stored there, the molecules are subsequently available for drug discovery using high-throughput screening.