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.
Lange
Kathrin
K
Lehrstuhl für Pharmazeutische/Medizinische Chemie, Institut für Pharmazie, Friedrich-Schiller-Universität Jena, Jena, Thuringia, Germany.
Koenig
Andreas
A
Roegler
Carolin
C
Seeling
Andreas
A
Lehmann
Jochen
J
D000818:Animals; D004897:Erythrityl Tetranitrate / Q000138:chemical synthesis / Q000378:metabolism* / Q000494:pharmacology; D020030:Nitric Oxide Donors / Q000138:chemical synthesis / Q000378:metabolism* / Q000494:pharmacology; D005996:Nitroglycerin / Q000138:chemical synthesis / Q000378:metabolism* / Q000494:pharmacology; D011651:Pulmonary Artery / Q000187:drug effects / Q000502:physiology; D013552:Swine; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000138:chemical synthesis / Q000378:metabolism* / Q000494:pharmacology
D020030:Nitric Oxide Donors; D014665:Vasodilator Agents; D004897:Erythrityl Tetranitrate; D005996:Nitroglycerin