ABSTRACT
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.
Subject(s)
Anti-Bacterial Agents/chemical synthesis , Cyclic S-Oxides/chemical synthesis , Oxazolidinones/chemical synthesis , Acetamides/pharmacology , Administration, Oral , Animals , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/toxicity , Biological Availability , Cyclic S-Oxides/pharmacology , Cyclic S-Oxides/toxicity , Dogs , Drug Resistance, Bacterial , Female , Gram-Negative Bacteria/drug effects , Gram-Positive Bacteria/drug effects , Injections, Intravenous , Linezolid , Male , Mice , Microbial Sensitivity Tests , Monoamine Oxidase Inhibitors/chemical synthesis , Monoamine Oxidase Inhibitors/pharmacology , Monoamine Oxidase Inhibitors/toxicity , Oxazolidinones/pharmacology , Oxazolidinones/toxicity , Rats , Rats, Sprague-Dawley , Staphylococcal Infections/drug therapy , Staphylococcus aureus , Streptococcal Infections/drug therapy , Streptococcus pyogenes , Structure-Activity RelationshipABSTRACT
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.
