In late 2008 (Drug Discovery World), Dr. Anil Vasudevan at Abbott Labs (Abbvie – oh what have they done to the name of my old hunting grounds) discussed how medicinal chemists have moved from traditional organic processes to SAR by microwave. Coupling technology changes, with the increased content in reaction databases, allowed the “lab rat” to produce more and more. In addition to a number of postulated future directions of the technology (i.e flow chemistry, in situ monitoring, etc), Anil focused on the impact of microwave speeding up the SAR process and suggested that to increase SAR cycles one would need the capability of evaluating multiple hypotheses in parallel. Certainly Abbott has developed one of the most efficient approaches to increasing their throughput capability with by coupling technologies (polymer supported reagents, flow-reactors) and established protocols to standardize the practice. That said, one of things about being an “efficient” medicinal chemist isn’t so much about how many analogs you can crank out in 30% yield in a one-step microwave process and finish by fishing the product out on the sequential HPLC, but to develop insight into how to cover the breadth of a core structure with multiple types of chemistry that can reach different positions on a core structure (flesh out) within the shortest amount of time.

One of the recent technology design improvements from a commercial microwave is a fundamental change in the way reactions are done. For the past 10-15 years we witnessed single-mode microwaves change the way medicinal chemists became faster because the instrumentation moved to automated robotic handling…..makes sense, right? As I remember, it did increase our throughput capacity — but as it goes, many times I would arrive at work to find the first 5 out of 20 worked and the unit shut down (and the pressure capability was pretty dismal). Multi-mode reactor designs enabled the possibility of performing reactions in parallel. For a core structure, with small changes in reactants, the throughput was increased. But this wasn’t the holy grail because you couldn’t change solvents or explore major changes in the chemistry because some changes would work….and other reactions didn’t heat up evenly or some would overheat above the control of a reference vessel.

Biotage Initiator

Single-mode Biotage Initiator

Multi-mode Anton Paar

Multi-mode Anton Paar

Modified Multi-mode SynthWAVE - Milestone

Modified Multi-mode SynthWAVE – Milestone

I have already posted on some research done using the SynthWAVE from Giancarlo Cravotto at the University of Turin. This fundamental change in the way both methods and reaction screening can be done should interest academic and medicinal chemists in several fields of study. The continuing advancement in microwave design is opening new avenues to conduct research.

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