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.

Applications of deuterium in medicinal chemistry

Pirali, Tracey
Primo
;
Serafini, Marta
Secondo
;
Cargnin, Sarah
Penultimo
;
Genazzani, Armando
Ultimo
2019-01-01

Abstract

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.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11579/99823
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