(S)-nadifloxacin and nadifloxacin

There is an urgent medical need for novel antibacterial agents to treat hospital infections, specially those caused by multidrug-resistant Gram-positive pathogens. The need may also be fulfilled by either exploring antibacterial agents having new mechanism of action or expanding known classes of antibacterial drugs. The paper describes a new chemical entity, compound 21, derived from hitherto little known "floxacin". The choice of the entity was made from a series of synthesized prodrugs and salts of the active chiral benzoquinolizine carboxylic acid, S-(-)-nadifloxacin. The chemistry, physicochemical characteristics, and essential bioprofile of 21 qualifies it for serious consideration as a novel drug entity against hospital infections of multi-drug-resistant Staphylococcus aureus, and its progress up to clinical phase I trials in humans is described.

Topics: Animals; Anti-Bacterial Agents; Area Under Curve; Clinical Trials, Phase I as Topic; Dogs; Drug Resistance, Multiple, Bacterial; Female; Fluoroquinolones; Half-Life; Humans; Infusions, Intravenous; Injections, Intravenous; Male; Methicillin Resistance; Mice; Microbial Sensitivity Tests; Mutation; Prodrugs; Quinolizines; Rats; Rats, Wistar; Staphylococcal Infections; Staphylococcus aureus; Stereoisomerism; Structure-Activity Relationship; Vancomycin Resistance