Abstract
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.
MeSH terms
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Animals
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Anti-Bacterial Agents / chemical synthesis*
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Anti-Bacterial Agents / pharmacology
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Anti-Bacterial Agents / toxicity
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Area Under Curve
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Clinical Trials, Phase I as Topic
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Dogs
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Drug Resistance, Multiple, Bacterial
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Female
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Fluoroquinolones / chemical synthesis*
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Fluoroquinolones / pharmacology
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Fluoroquinolones / toxicity
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Half-Life
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Humans
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Infusions, Intravenous
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Injections, Intravenous
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Male
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Methicillin Resistance
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Mice
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Microbial Sensitivity Tests
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Mutation
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Prodrugs / chemical synthesis
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Prodrugs / pharmacology
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Prodrugs / toxicity
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Quinolizines / chemical synthesis*
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Quinolizines / pharmacology
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Quinolizines / toxicity
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Rats
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Rats, Wistar
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Staphylococcal Infections / drug therapy
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Staphylococcus aureus / drug effects*
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Staphylococcus aureus / genetics
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Stereoisomerism
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Structure-Activity Relationship
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Vancomycin Resistance*
Substances
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Anti-Bacterial Agents
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Fluoroquinolones
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Prodrugs
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Quinolizines
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nadifloxacin