High Throughput and High Speed Organic Synthesis in Drug Discovery: An Integration of Chemistry and Technology

Drug discovery is a complicated process that involves multiple synthetic chemistry tasks.Among them, lead generation and optimization is the core business in the discovery research.During the stage of lead generation, a large library of many thousands individual compounds will be screened against a biological target to identify a set of hits that showed desirable activity. Once a hit has been identified, analog synthesis and development of SAR around this hit and establishment of relationship between targeted protein and its cellular function become the key activity in the drug discovery project. During this process, focused libraries of a few hundred compounds (X00) will be synthesized and tested. For synthetic chemistry tasks, the efficiency can be enhanced through "parallel processing or high throughput chemisay" using automation technology with which a large number of compounds can be synthesized, purified and plated at same time for biological and pharmaceutical screenings. To accelerate the lead optimization high speed synthesis is conducted when necessary and to improve "single process" efficiency using automation technology, when the rate limiting step become developing synthetic method to produce large amount of compounds (in gram quantity) that can be used in vivo pharmacology study. With these in mind, we designed integrated HTC technology platform which supports the key chemical synthesis activities in discovery research. In this presentation, several examples will be presented to illustrate the applications of high throughput and high speed organic synthesis in drug discovery.