RESUMEN
Oxazolidinones possessing a C-5 carboxamide functionality (reverse amides) represent a new series of compounds that block bacterial protein synthesis. These reverse amides also exhibited less potency against monoamine oxidase (MAO) enzymes and thus possess less potential for the side effects associated with MAO inhibition. The title compound (14) showed reduced in vivo myelotoxicity compared to linezolid in a 14-day safety study in rats, potent in vivo efficacy in murine systemic infection models, and excellent pharmacokinetic properties.
Asunto(s)
Antibacterianos/síntesis química , Óxidos S-Cíclicos/síntesis química , Oxazolidinonas/síntesis química , Acetamidas/farmacología , Administración Oral , Animales , Antibacterianos/farmacología , Antibacterianos/toxicidad , Disponibilidad Biológica , Óxidos S-Cíclicos/farmacología , Óxidos S-Cíclicos/toxicidad , Perros , Farmacorresistencia Bacteriana , Femenino , Bacterias Gramnegativas/efectos de los fármacos , Bacterias Grampositivas/efectos de los fármacos , Inyecciones Intravenosas , Linezolid , Masculino , Ratones , Pruebas de Sensibilidad Microbiana , Inhibidores de la Monoaminooxidasa/síntesis química , Inhibidores de la Monoaminooxidasa/farmacología , Inhibidores de la Monoaminooxidasa/toxicidad , Oxazolidinonas/farmacología , Oxazolidinonas/toxicidad , Ratas , Ratas Sprague-Dawley , Infecciones Estafilocócicas/tratamiento farmacológico , Staphylococcus aureus , Infecciones Estreptocócicas/tratamiento farmacológico , Streptococcus pyogenes , Relación Estructura-ActividadRESUMEN
The cascade from tides to turbulence has been hypothesized to serve as a major energy pathway for ocean mixing. We investigated this cascade along the Hawaiian Ridge using observations and numerical models. A divergence of internal tidal energy flux observed at the ridge agrees with the predictions of internal tide models. Large internal tidal waves with peak-to-peak amplitudes of up to 300 meters occur on the ridge. Internal-wave energy is enhanced, and turbulent dissipation in the region near the ridge is 10 times larger than open-ocean values. Given these major elements in the tides-to-turbulence cascade, an energy budget approaches closure.
