Recent Developments in Antibacterial 4-Quinolone-3-carboxylic Acids

During the past decade, the synthesis of new 4-quinolone-3-carboxylic acids and the evaluation of their antibacterial activities have continued, and the roles of DNA gyrase and topoisol1erase IV have been well defined. Several of the structure-activity relationships regarding the side-chain at C-7, the effect of halogen or methoxy groups at C-8, and the effect of the C-5 amino group were greatly influenced by the choice of the N-l substituent. The spectrum and potency of the C-7 piperazinyl and pyrrolidinyl quinolones was greatly enhanced by the judicious choice of C-5, C-8, and N-I substituents. Although it was initially thought that the C-6 fluoro group was re-sponsible for enhanced bacterial penetration and DNA gyrase inhibition, it has been discovered that compounds without this component also display broad and potent antimicrobial activity. Therefore, the appropriate term for these newer antibacterial agents is suggested to be 4quinolone-3-carboxylic acids.