RESUMEN
The enantiomers of glyceryl-1-nitrate, a metabolite of glyceryl trinitrate, were pharmacologically characterized in vitro and in animals. In the Langendorff heart (l) G-1-N was double as potent as (d) G-1-N with respect to the enhancement of coronary flow. The two enantiomers showed almost the same dose-response curves in rabbit aortic strips contracted with phenylephrine. In the same model there were no enantiospecific differences in the development of cross-tolerance to glyceryl-trinitrate. In anaesthetized rabbits, intravenous (l) G-1-N reduced the blood pressure slightly more than (d) G-1-N, while in the conscious dog the blood pressure lowering effect of (d) G-1-N was greater and had a much longer duration (4-6 versus 2 h) than that of (l)G-1-N. The differences in dogs are probably explained by enantiospecific pharmacokinetics: (d) G-1-N had higher plasma levels and showed a longer half-life of elimination than (l) G-1-N (more than 5 h versus 2.7 h). Both enantiomers enhanced the rate of survival after acute coronary ligature in rats with a tendency to higher long-term survival rates after the (d) form.
Asunto(s)
Nitroglicerina/análogos & derivados , Administración Oral , Animales , Presión Sanguínea/efectos de los fármacos , Chinchilla , Circulación Coronaria/efectos de los fármacos , Perros , Tolerancia a Medicamentos , Femenino , Cobayas , Semivida , Corazón/efectos de los fármacos , Frecuencia Cardíaca/efectos de los fármacos , Técnicas In Vitro , Masculino , Contracción Miocárdica/efectos de los fármacos , Nitroglicerina/farmacocinética , Nitroglicerina/farmacología , Conejos , Ratas , Ratas Sprague-Dawley , EstereoisomerismoRESUMEN
Several hybrid molecules have been synthesized which contain both the 1,4:3,6-dianhydro-hexitol (isohexide) and glycerol partial structures, with nitrate ester groups at different positions. Alkylation of the isohexide ring system with suitable 3-carbon units generates compounds with the 2,3-epoxypropyl side chain as key intermediates. Ring opening of these oxiranes under various conditions yield primary and secondary nitrates as well as dinitrates. Pharmacological screening shows that the new structures are much less active than the parent compounds.
Asunto(s)
Cardiotónicos/síntesis química , Nitratos/síntesis química , Alcoholes del Azúcar/síntesis química , Fenómenos Químicos , Química , Electrocardiografía , Nitratos/farmacología , Estereoisomerismo , Relación Estructura-Actividad , Alcoholes del Azúcar/farmacologíaAsunto(s)
Angina de Pecho/tratamiento farmacológico , Compuestos Bicíclicos con Puentes/síntesis química , Hidrocarburos Aromáticos con Puentes/síntesis química , Alcoholes Grasos/síntesis química , Nitratos/síntesis química , Animales , Compuestos Bicíclicos con Puentes/farmacología , Fenómenos Químicos , Química , Alcoholes Grasos/farmacología , Dinitrato de Isosorbide/farmacología , Nitratos/farmacología , RatasRESUMEN
Several uracil and cytosine nucleoside analogues with 2-hydroxyethoxymethyl, 2-aminoethoxymethyl or 1,3-dihydroxypropoxymethyl side chains were synthesized and evaluated for cytostatic (L5178y mouse lymphoma cells) and antiviral (herpes simplex virus type 1 infected KB cells) activity. Two compounds exhibited antiherpesvirus activity. These were 1-(2'-hydroxyethoxymethyl)-5-aza-cytosine and 1-(1',3'-dihydroxypropoxymethyl)-5-iodouracil. The MIC values were 25.8 and 325.7 micrograms/ml, respectively.