Enabling Synthetic Technologies for Chemical Libraries, Hit Optimization and Scale-up: In-flow Synthesis and Biological Activity of Quinoline-based Compounds

In the changing landscape of drug discovery, technological innovation in synthesis is playing a crucial role from early phase of lead identification to production. Nowadays, synthetic strategies are designed to be versatile for a fast access to chemical libraries and, at the same time, easily scalable to support in vivo efficacy, safety testing, and clinical trials. The increasing number of reports and publications, the capital investments of pharmaceutical industries, and the availability of commercial equipments are qualifying continuous flow technology particularly suitable for these purposes. The potential advantages of the flow chemistry include high control of the reaction variables, which can translate into higher product quality; increased safety and ecosustainability; possibility of conduct reactions at supercritical conditions; feasibility of automation reducing manual handling and accelerating products throughput; reproducibility and easy scale-up; possibility of in-line purification, analysis and reaction telescoping; process intensification resulting in a smaller footprint in a manufacturing plant. In this communications, our recent efforts directed towards the set-up and implementation of integrated flow platforms developed to accelerate the total compound-generation, to improve chemical processes, as well as to decrease the instrument face time by the operating scientist, will be presented. In particular, the prototype systems will be exemplifyed by case studies within our medicinal chemistry programmes showing the potential to reduce significantly the time and cost of preclinical drug discovery.