The purpose of medicinal chemistry is to deliver molecular probes for understanding biological processes and targets. The use of such tools in chemical biology, pharmacology, and medicine is fundamental to define novel therapeutic approaches and discover new drugs. However, small-molecule drug discovery remains an enormous challenge in which various compounds characteristics, as the potency, in vivo efficacy and safety, need to be fine-tuned to provide clinical candidates. To this aim, molecular design, synthesis, characterization, and testing are conducted iteratively to generate structure-activity and structure-property relationship data for compound optimization. Using traditional approaches, this process generally requires time and resources. Moreover, delay may occur from design hypothesis to results leading to slow explorations, limited number of leads candidates, and high costs. Recent advances in chemical technologies, computational methods, and biological testing have shown the potential to accelerate compound discovery and development. In particular, the use of flow chemistry has expedited compound-generation by means of synthetic platforms that can be coupled with bio-assays and predictive tools for hit-to-lead explorations. Moreover, by integrating the flow reactor module, process control devices and in-line analysis, it has been also possible to design autonomous prototypes capable of reaction optimization and telescoped multistep synthesis of lead compounds to be advanced in (pre)clinical settings. Overall, such an approach has introduced new operational paradigms and alternate solutions to support early phase drug discovery and development efforts.
Medicinal Chemistry Powered by Continuous Flow Technology – a Multifaceted Toolbox for Compound Library Building and Scale-up Processes
Gioiello A
2018
Abstract
The purpose of medicinal chemistry is to deliver molecular probes for understanding biological processes and targets. The use of such tools in chemical biology, pharmacology, and medicine is fundamental to define novel therapeutic approaches and discover new drugs. However, small-molecule drug discovery remains an enormous challenge in which various compounds characteristics, as the potency, in vivo efficacy and safety, need to be fine-tuned to provide clinical candidates. To this aim, molecular design, synthesis, characterization, and testing are conducted iteratively to generate structure-activity and structure-property relationship data for compound optimization. Using traditional approaches, this process generally requires time and resources. Moreover, delay may occur from design hypothesis to results leading to slow explorations, limited number of leads candidates, and high costs. Recent advances in chemical technologies, computational methods, and biological testing have shown the potential to accelerate compound discovery and development. In particular, the use of flow chemistry has expedited compound-generation by means of synthetic platforms that can be coupled with bio-assays and predictive tools for hit-to-lead explorations. Moreover, by integrating the flow reactor module, process control devices and in-line analysis, it has been also possible to design autonomous prototypes capable of reaction optimization and telescoped multistep synthesis of lead compounds to be advanced in (pre)clinical settings. Overall, such an approach has introduced new operational paradigms and alternate solutions to support early phase drug discovery and development efforts.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
