Relationship between structure and antibacterial activity in the fluoroquinolone series of compounds

The class of derivatives of 4-oxoquinoline-and4-oxo-1,8-naphthyridine-3-carboxylic acids and related heterocyclic compounds contains a large group of substances used in medical practice as antibacterial drugs with a broad spectrum of action. Studies in this field were summarized in a number of monographs and reviews [1 -7]. More that three decades of investigation of this group of compounds resulted in the development of four generations of antibacterial drugs offering a broad spectrum of action, with the efficiency increasing from one generation to another. The current generation of these compounds comprises the so-called fluoroquinolone preparations representing compounds containing fluorine atoms in position 6 of the quinoline, naphthyridine, or any other related nucleus. Most characteristic representatives of this group are the commercial drugs ciprofloxacin, ofloxacin, and lomefloxacin. Similar to most other drugs, preparations of the 4-oxoquinoline-3-carboxylic acid group, including the fluorine-containing derivatives, exhibit certain side effects that may sometimes restrict their practical application [7].Extensive investigations into the series of derivatives of 4-oxoquinoline-and 4-oxo-l,8-naphthyridine-3-carboxylic acids, performed to the present time, allowed certain "structure-activity" relationships in this group to be established and some substituents and their positions in the base mole--cules to be determined that impart the maximum antibacterial activity to the final compounds. For example, most active eompotmds are distingxtished by having fluorine atoms as substituents in position 6 of the quinoline or related nucleus. Fluorine and other substituents favoring antibacterial activity are described by the following sequence: F > C1 > Br = Me = CN > SMe = NO2>Ac. The most preferred substituents in po-

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“…sition 1 of the quinoline cycle are alkyl (cyclopropyl, ethyl) and 4-fluoro-or 2,4-difluorophenyl [5,6,8].…”

mentioning

confidence: 99%

Synthesis and amination of 1-alkyl-6-nitro-4-oxo-7-chloro-1,4-dihydroquinoline-3-carboxylic acids

Глушков¹,

Marchanko²,

Levshin³

et al. 1997

Pharm Chem J

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“…2-Mercapto-5,6-difluorobenzimidazole 1 was shown to react with aromatic α-haloketones to give 2-phenacylthio-5,6-difluorobenzimidazoles 2. The latter were transformed by acylation and cyclodehydration in an acetic anhydride-pyridine system into benzo [4,5] [13]. Biological tests revealed that compound 4 (Ar = C 6 H 5 ) displayed a considerable activity toward the meastle virus [14].…”

Section: Fluorinated Benzazolesmentioning

confidence: 98%

“…It is worth noting that (S)-naproxen chloride, N-sulfonyl-substituted (R)-proline, and (2S)-(6-methoxynapht-2-yl)propionyl chloride were found to be appropriate agents for kinetic resolution of a racemic mixture of 7,8-difluoro-2,3-dihydro-3-methyl-4H [1,4] The second approach suggests using fluorinated benzoyl derivatives (34, A = CF, CH) or their nicotinoyl analogs (34, A = N) as starting materials and involves the formation of benzoyl acrylates 36 as the key intermediates (Scheme 13).…”

Section: Fluorinated Benzazinesmentioning

confidence: 99%

“…The carboxylic group in position 3 of fluoroquinolones can be replaced with other substituents to obtain new antibacterials [4], and many modifications of this type have been carried out. For instance, hydrazino derivatives of fluoroquinolones 57 were found to react with potassium ethylxantogenate to give 3-heteryl(oxadiazolyl) derivatives of quinolonecarboxylic acids 58 (Scheme 18) [56].…”

Section: Fluorinated Benzazinesmentioning

confidence: 99%

“…have been advanced [2]. A great deal of publications focus on structural modifications of fluoroquinolones as inhibitors of the DNA-gyrase (bacterial topoisomerase), the enzyme that is responsible for cleavage and renovation of the double helix of bacterial DNA [3][4][5]. It has been shown that fluoroquinolones can influence the eucariot cells, sometimes showing a high cytotoxicity, and thus being of interest as anticancer agents [6,7].…”

Section: Introductionmentioning

confidence: 99%

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