Precision deuteration has become part of the medicinal chemist's toolbox, but its usefulness can be undermined by unpredictable metabolic switch effects. Herein we report the deuteration of doxophylline, a drug used in the treatment of asthma and COPD that undergoes extensive oxidative metabolism. Labeling of the main metabolic soft spots triggered an unexpected multidirectional metabolic switch that, while not improving the pharmacokinetic parameters, changed the metabolic scenario and, in turn, the pharmacodynamic features in two murine models of lung injury.

An Unexpected Deuterium-Induced Metabolic Switch in Doxophylline

Aprile, Silvio
Primo
;
Colombo, Giorgia;Serafini, Marta;Bhela, Irene Preet;Grosa, Giorgio;Pirali, Tracey
2022-01-01

Abstract

Precision deuteration has become part of the medicinal chemist's toolbox, but its usefulness can be undermined by unpredictable metabolic switch effects. Herein we report the deuteration of doxophylline, a drug used in the treatment of asthma and COPD that undergoes extensive oxidative metabolism. Labeling of the main metabolic soft spots triggered an unexpected multidirectional metabolic switch that, while not improving the pharmacokinetic parameters, changed the metabolic scenario and, in turn, the pharmacodynamic features in two murine models of lung injury.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11579/146359
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