The identification of a lead compound through iterative generation of structure-activity relationship (SAR) data is at the core of early-stage drug discovery. A complete SAR cycle is composed of organic synthesis, compound purification, chemical structure confirmation, biological evaluation and data analysis. The workflow for generation of SAR data is usually distributed across highly specialized facilities and biological data on a new chemical structure is rarely available prior to one week after its synthesis. Parallelization of chemical synthesis and bioassaying has been the most common solution but remains largely cost-intensive due to lack of real-time feedback and consequential generation of irrelevant chemical examples. Thus, there is an imminent unmet need for merging chemical, analytical and biological procedures into a single continuous process that minimizes spatio-temporal barriers and fosters a cost-efficient lead discovery process. After a short general introduction to flow synthesis we demonstrate the seamless integration of a flow-compatible beta-secretase inhibition assay into a fully automated chemical flow synthesis and analysis platform that allows the generation of complete SAR cycles within 60 min from injection of the starting materials to generation of IC<sub>50</sub> values.

From synthesis in flow to integrated dose-response screening in flow

249th National Meeting (2015)

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