Quinolones: structure-activity relationships and future predictions

Abstract

Development of the first clinically useful quinolone--nalidixic acid-- occurred in 1962, but the significant breakthrough with this class of agents occurred almost 20 years after the original discovery when the addition of a fluorine molecule at position C6 of the pharmacore created the 'fluoroquinolones'. It has been estimated that over 10000 analogues of nalidixic acid or the fluoroquinolones have now been synthesised. The benefits of some of these new compounds include: oral and parenteral dosing, a much broader spectrum of antibacterial activity, good tissue distribution, improved pharmacokinetic profiles, stability and a comparatively low incidence of adverse effects. This review considers the structure of the core fluoroquinolone molecule, some of the changes that feature on current class members under development, and the effects that these chemical modifications may have on the interaction of these compounds with man.