Set-up and assessment of flow systems for streamlined synthesis and medicinal chemistry

Over the past two decades, the advent of technological innovation in synthesis has been of crucial importance to fulfil the criteria and needs of modern drug discovery. Novel concepts and strategies have been adopted to enable the rapid assembly of compounds collections available for screenings and the production of clinical candidates to support in vivo efficacy and safety testing. Among chemical technologies, continuous flow chemistry has proven particularly suitable for these purposes offering new solutions and several advantages over more traditional approaches. The ability to easily scale-up reactions led to a major impact of flow systems on the development of lead compounds reducing re-synthesis times, and most recently being further applied to manufacturing processes of marketed drugs. This talk deals with the set-up and implementation of flow strategies designed to accelerate the total compound generation for the biological screening of druggable targets, as well as with the optimization of multistep flow processes for the preparation of lead compounds to be advanced in (pre)clinical studies (Figure 1). The integration of continuous flow synthesis with computational tools, automated purifications, and in-line analysis will be exemplified by case studies that show the potential of these systems to improve performance, product quality and throughput, automation, safety standards with the concomitant reductions in cost and waste generation.