Details

Autor(en) / Beteiligte

• Aprile, Silvio
• Colombo, Giorgia
• Serafini, Marta
• Di Paola, Rosanna
• Pisati, Federica
• Bhela, Irene Preet
• Cuzzocrea, Salvatore
• Grosa, Giorgio
• Pirali, Tracey

Titel

An Unexpected Deuterium-Induced Metabolic Switch in Doxophylline

Ist Teil von

• ACS medicinal chemistry letters, 2022-08, Vol.13 (8), p.1278-1285

Ort / Verlag

United States: American Chemical Society

Erscheinungsjahr

2022

Link zum Volltext

Quelle

Electronic Journals Library

Beschreibungen/Notizen

• 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.