620-12-2Relevant academic research and scientific papers
NO donors. Part 18: Bioactive metabolites of GTN and PETN-Synthesis and vasorelaxant properties
Lange, Kathrin,Koenig, Andreas,Roegler, Carolin,Seeling, Andreas,Lehmann, Jochen
experimental part, p. 3141 - 3144 (2010/01/17)
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.
Reduction of nitroglycerin with elemental iron: Pathway, kinetics, and mechanisms
Oh, Seok-Young,Cha, Daniel K.,Kim, Byung J.,Chiu, Pei C.
, p. 3723 - 3730 (2007/10/03)
Nitroglycerin (NG) is a nitrate ester used in dynamites, propellants, and medicines and is therefore a common constituent in propellant-manufacturing and pharmaceutical wastewaters. In this study we investigated the reduction of NG with cast iron as a potential treatment method. NG was reduced stepwise to glycerol via 1,2- and 1,3-dinitroglycerins (DNGS) and 1- and 2-mononitroglycerins (MNGs). Nitrite was released in each reduction step and was further reduced to NH4+. Adsorption of NG and its reduction products to cast iron was minimal. A reaction pathway and a kinetic model for NG reduction with cast iron were proposed. The estimated surface area-normalized reaction rate constants for NG and NO2- were (1.65 ± 0.30) × 10-2 (L·m -2·h-1) and (0.78 ± 0.09) × 10 -2 (L·m-2·h-1), respectively. Experiments using dialysis cell with iron and a graphite sheet showed that reduction of NG to glycerol can be mediated by graphite. However, reduction of NO2- mediated by graphite was very slow. NG and NO 2- were also found to reduce to glycerol and NH 4+ by Fe2+ in the presence of magnetite but not by aqueous Fe2+ or magnetite alone. These results indicate that in a cast iron-water system NG may be reduced via multiple mechanisms involving different reaction sites, whereas nitrite is reduced mainly by iron and/or adsorbed Fe2+. The study demonstrates that iron can rapidly reduce NG to innocuous and biodegradable end products and represents a new approach to treat NG-containing wastewaters.
STUDY OF NITRATION EQUILIBRIUM IN THE GLYCERIN-AQUEOUS NITRIC ACID SYSTEM. 1. DEPENDENCE OF THE EQUILIBRIUM CONSTANTS OF NITRATION REACTIONS ON THE TEMPERATURE, ACIDITY OF THE MEDIUM, AND STRUCTURE OF THE NITRATED COMPOUND
Kazakov, A. I.,Lagodzinskaya, G. V.,Andrienko, L. P.,Yunda, N. G.,Korolev, A. M.,et al.
, p. 1560 - 1565 (2007/10/02)
The equilibrium constants of seven sequential-parallel reactions of conversion of glycerin into glycerin trinitrate in aqueous HNO3 were measured.The effect of the acidity of the medium on the equilibrium nitration constants is correlated with processes of protonation of glycerin and its nitrates.The equilibrium nitration constants are higher for primary hydroxides than for secondary hydroxides, and they decrease in both series in going from glycerin to its dinitrates.
STUDY OF NITRATION EQUILIBRIUM IN THE GLYCERIN-AQUEOUS NITRIC ACID SYSTEM. 2. CHANGES IN ΔH AND ΔS IN THE NITRATION REACTION
Kazakov, A. I.,Kirpichev, E. P.,Lagodzinskaya, G. V.,Andrienko, L. P.,Yunda, N. G.,et al.
, p. 1565 - 1570 (2007/10/02)
The real enthalpies of seven sequential-parallel reactions of nitration of glycerin into glycerin trinitrate were found by combination of the heats of the reactions obtained by the thermochemical method and with the equation for the isobar of the chemical reaction, and the standard enthalpies of formation of glycerin nitrates were calculated with them.The difference in the enthalpies of nitration with respect to different positions in glycerin and its nitrates basically determines the difference in the corresponding equilibrium constants of the nitration reactions.
The pattern of glyceryl nitrates after oral administration of glyceryl trinitrate.
Laufen,Leitold
, p. 103 - 105 (2007/10/02)
An oral dose of 20 mg sustained release glyceryl trinitrate (GTN, Nitro Mack Retard) was administered to 6 healthy human subjects. In the plasma of all subjects the metabolically generated glyceryl nitrates glyceryl 1,2-dinitrate (G-1,2-DN), glyceryl 1,3-dinitrate (G-1,3-DN), glyceryl 2-nitrate (G-2-N) and glyceryl (G-1-N) could be identified, but no intact GTN was found. The nitrate metabolites showed sustained plasma profiles which can be explained by a slow release of GTN with subsequent complete first-pass denitration. The plasma concentrations of the mononitrates were generally higher than those of the dinitrates. G-1,2-DN and G-2-N, the metabolites which contain a nitrate group in the central position, showed higher concentrations than the respective isomeric compounds. The combined glyceryl dinitrates reached concentrations between 10.2 and 21.7 ng/ml, the combined mononitrates varied from 70.4 to 106.8 ng/ml. The ratios of the areas under the curve G-1,3-DN:G-1,2-DN:G-1-N:G-2-N were 1:4:19:64, on average. Taking into consideration the relative vasodilator potencies of glyceryl nitrates in the animal, our results give rise to the hypothesis that the glyceryl dinitrate metabolites participate in the clinical efficacy of large oral doses of sustained release GTN.
