NO donors. Part 18: Bioactive metabolites of GTN and PETN—Synthesis and vasorelaxant properties

The vasodilators glyceryl trinitrate (GTN) and pentaerythrityl tetranitrate (PETN) are supposed to be degraded in vivo to the lower nitrates PETriN, PEDN, PEMN, 1,2-GDN, 1,3-GDN, 1-GMN, and 2-GMN. We synthesized these bioactive metabolites as reference compounds for pharmacokinetic studies. The use of HPLC-methods for monitoring the stepwise reduction of PETN to lower nitrates and the syntheses of the glyceryl dinitrates proved advantageous. Furthermore, we measured the vasorelaxant properties of all metabolites by performing organ bath experiments with porcine pulmonary arteries. In general, the vasodilator potency increases with the number of nitrate moieties in the compound.

Graphical abstractThe bioactive metabolites of GTN and PETN were synthesized and their vasorelaxant potencies measured by performing organ bath experiments with porcine pulmonary arteries.Figure optionsDownload full-size imageDownload as PowerPoint slide