Applications of deuterium in medicinal chemistry

The use of deuteration in medicinal chemistry has exploded in the last years and the FDA has recently approved the first deuterium-labelled drug. Precision deuteration goes beyond the pure and simple amelioration of the pharmacokinetic parameters of a drug and might provide an opportunity when facing problems in terms of metabolism-mediated toxicity, drug interactions and low bioactivation. The use of deuterium is even broader, offering the opportunity to lower the degree of epimerization, reduce the dose of co-administered boosters and discover compounds where deuterium is the basis for the mechanism of action. Nevertheless, designing, synthesizing and developing a successful deuterated drug is far from straightforward, and the translation from concept to practice is often unpredictable. This perspective provides an overview of the recent developments of deuteration, with a focus on deuterated clinical candidates, and highlights both opportunities and challenges of this strategy.