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.
MeSH terms
-
Acetamides / pharmacology
-
Administration, Oral
-
Animals
-
Anti-Bacterial Agents / chemical synthesis*
-
Anti-Bacterial Agents / pharmacology
-
Anti-Bacterial Agents / toxicity
-
Biological Availability
-
Cyclic S-Oxides / chemical synthesis*
-
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 / chemical synthesis*
-
Oxazolidinones / pharmacology
-
Oxazolidinones / toxicity
-
Rats
-
Rats, Sprague-Dawley
-
Staphylococcal Infections / drug therapy
-
Staphylococcus aureus
-
Streptococcal Infections / drug therapy
-
Streptococcus pyogenes
-
Structure-Activity Relationship
Substances
-
Acetamides
-
Anti-Bacterial Agents
-
Cyclic S-Oxides
-
Monoamine Oxidase Inhibitors
-
Oxazolidinones
-
PF 00422602
-
Linezolid