Fleroxacin

Quinolone-Gephalosporin Godrugs. Quinolones have been covalently linked to cephalosporins in order to generate a codmg containing one molecule of each type of antibacterial agent. An example is the fleroxacin—cefotaxime [63527-52-6] combination, Ro 23-9424 [115622-58-7] (23). 

C5H12N2 109-01-3) see Azimilide hydrochloride Chlorcyclizine Clozapine Cyclizine Diethylcarbamazine Fleroxacin Hexocyclium metilsulfate Levofloxacin Loprazolam Loxapine Ofloxacin Olanzapine Pefloxacin Perlapine Pipebuzone Pirenzepine Prochlorperazine Rufloxacin hydrochloride Sildenafil Tiotixene... 

P. Jynge, T. Skjetne, I. Gribbestad, C.H. Kleinbloesem, H.F.W. Hoogkamer, O. Antonsen, J. Krane, O.E. Bakoy, K.M. Furuheim, O.G. Nilsen, In vivo tissue pharmacokinetics by fluorine magnetic-resonance spectroscopy—a study of liver and muscle disposition of fleroxacin in humans, Clin. Pharmacol. Then 48 (1990) 481-489. 

Flash photolysis of fleroxacin 365 in water gave a mixture of 7-oxo-2,3-dihydro-7H-pyrido[l,2,3-de][l,4]oxazine-6-carboxylic acid 366 and 4-oxo-l,4-dihydroquinolone-3-carboxylic acids 367 and 368 (09OL1875). 

The breakthrough in the development of quinolones came with the appearance of norfloxacin 6 [19], a second-generation quinolone which combined a 6-fluorine substituent with a piperazine ring in the 7-position of the basic compound. Additional quinolones then followed in rapid succession pefloxacin [20], enoxacin [21] and fleroxacin [22] (Fig. 14.5). Particular mention must be made of ciprofloxacin 8 [23-25], ofloxacin 5 [26,27] and its active enantiomer levofloxacin 7 [28]. These quinolones have a broad spectrum of activity, which also includes Gram-positive bacteria and Pseudomonas aeruginosa, as well as favorable pharmacokinetics. The rapid absorption of these compounds from the gastrointestinal tract and their effective tissue penetration also allows them to be used for the treatment of systemic infections. 

At the start of and during the search for a third-generation quinolone, most of the commercially available quinolones contained an optionally substituted piperazinyl radical in the 7-position (Fig. 14.5). Of these compounds, only norfloxacin, pefloxa-cin, ofloxacin, levofloxacin, ciprofloxacin, enrofloxacin, marbofloxacin, danofloxacin and gatifloxacin still play a role today. The 6,8-difluoroquinolones fleroxacin, spar-floxacin and lomefloxacin, as well as grepafloxacin and temafloxacin, were of little importance or withdrawn from the market due to their adverse side effects [68,69]. 

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