Pfizer’s chemistry machine

How Pfizer is bringing continuous flow to medicinal chemistry

With the goal of creating a step-change in the optimization of small molecules in discovery research, Pfizer Inc. has built a continuous flow machine that rapidly tests thousands of chemical reactions using submilligram quantities of starting material. The goal is to bring the optimization process upstream in drug development and reduce the amount of reinventing the wheel on compound synthesis that occurs later in CMC.

Although combinatorial chemistry has become commonplace throughout the industry and enabled construction of large compound libraries, the standard methods still limit the options available to medicinal chemists for optimizing molecules early in drug discovery.

Most systems rely on generalizable coupling strategies to link chemical building blocks, but designing efficient methods that will scale is limited by the availability of starting material. In particular, dialing in the right solvent, temperature, pressure, catalyst and other conditions for the couplings can take many iterations.

Consequently, chemists often make small molecules for research under suboptimal conditions that don’t easily scale. Some reactions never get solved under any conditions, limiting the chemical space.

Last month in Science, Pfizer published a study outlining a continuous flow system to accelerate compound optimization and enable bench-scale reactions normally beyond reach.

“Over the last 20 years, spurred by the combinatorial revolution, we started to run 10-20 reactions per day.

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