Speeding up Early Phases of Drug Discovery: DoE-Driven Synthetic Optimization of Chemical Processes in Flow Systems

In recent years, medicinal and synthetic chemistry have experienced a significant evolution in the approaches used and general thinking. Several research groups from both academia and within pharmaceutical companies have adopted more technological solutions to help the delivery of compounds from early phases of discovery to (pre)clinical investigations and drug production. Modern chemical manufacturing companies and academic laboratories are investing resources to drive a radical innovation in synthetic technologies, which would enable the conduction of chemical transformations that are difficult or impossible to be realized because of safety restriction, timing, costs, and environmental impact. Within this changing landscape, flow chemistry has rapidly emerged as a key technique that can significantly support these efforts leading to a radical change on how chemists think, perform and optimize chemical synthesis. In this communication, we have combined the potentiality of flow systems with automated equipment and software for the generation of compounds library and lead candidates advanced in preclinical settings of ischemia and cancer. In particular, the profitable use of statistical design of experiments (DoE) will be demonstrated as a valuable tool to understand the benefits and risks associated with the chemical process and to speed up the synthetic optimization through a careful selection of experiments and the interpretation and validation of the results obtained.