Development of the quinolones

Abstract

Since their discovery in the early 1960s, the quinolone group of antibacterials has generated considerable clinical and scientific interest. Nalidixic acid, the first quinolone to be developed, was obtained as an impurity during the manufacture of quinine. Since this time, many derivatives have been synthesized and evaluated for their antibacterial potency. Two major groups of compounds have been developed from the basic molecule: quinolones and naphthyridones. Manipulations of the basic molecule, including replacing hydrogen with fluorine at position 6, substituting a diamine residue at position 7 and adding new residues at position 1 of the quinolone ring, have led to enhanced antibacterial efficacy. In general these compounds are well tolerated. However, some of these structural changes have been found to correlate with specific adverse events: the addition of fluorine or chlorine at position 8 being associated with photo-reactivity, e.g. Bay y 3118 and sparfloxacin; and the substitution of an amine or a methyl group at position 5 having a potential role in QTc prolongation, e.g. sparfloxacin and grepafloxacin. Progressive modifications in molecular configuration have resulted in improved breadth and potency of in vitro activity and pharmacokinetics. One of the most significant developments has been the improved anti-Gram-positive activity of the newer compounds, such as moxifloxacin and garenoxacin. In the current millennium, these new agents may play an important role in the treatment of respiratory infections.

Crystal structure of bis(1-ethyl-6-fluoro-4-oxido-7-(piperazin-1-ium-1-yl)-1,8-naphthyridin-1-ium-3-carboxylate-κ2 O,O′)copper(II) benzene-1, 4-dicarboxylate dihydrate, C38H42F2CuN8O12

“…Enoxacin (Henox), C15H17F 2 N4O 3 (systematic name 1-ethyl-6-uoro-1,4-dihydro-4-oxo-7-(1-piperazinyl)-1,8-naphtyridine-3-carboxylic acid) is a member of the uoroquinolone ( qu) family of antibiotics, widely used in veterinary clinical practice because of its wide antibiotic spectrum and its excellent bactericidal activity [1]. Our interest in enoxacin and related uoroquinolones is focused on their potential as multidentate/bridging ligands in coordination chemistry.…”

Crystal structure of diaquabis[1-cyclopropyl-7-(4-ethylpiperazin-1-yl)-6- fluor-4-oxo-1,4-dihydrochinolin-3-carboxylato-κ2O,O']cobalt(II) bis(1- carboxy-4-carboxylatebenzene octahydrate, [Co(C19H22N3FO3)2(H2O)2]·2(C8H5O4)·8(H2O), C54H74CoF2N6O24

“…Enrofloxacin (Henro),C 19 H 22 FN 3 O 3 (systematic name 1-cyclopropyl-7-(4-ethylpiperazin-1-yl)-6-fluor-4-oxo-1,4-dihydrochinolin-3-carboxylic acid), is amember of the fluoroquinolone (flqu)f amily of antibiotics, widely used in veterinary clinical practice becauseofits wide antibiotic spectrum andits excellent bactericidal activity [1]. Our interest in enrofloxacinand related fluoroquinolones is focused on their potential useasmultidentate bridgingligands in coordination chemistry.…”

Quinolone Antibacterials: Commentary and Considerations Regarding UV Spectra and Chemical Structure

“…The evolution of quinolones began with the introduction in therapy of the nalidixic acid (NAL) in 1962 for the treatment of urinary tract infections. After the discovery of NAL a series of quinolones having a 1-substituted-1,4-dihydro-4-oxopyridine-3-carboxyilic structure have been developed (Figure 1), but the real breakthrough began with the introduction of fluoroquinolones, which have a fluorine atom attached to the central ring system, typically at the C-6-position [1].…”