Pefloxacin

Pefloxacin (33) is the N-methyl analogue of norfloxacin (58) and is at least partly converted to it by metabolic enzymes in vivo. It has been launched in France for the treatment of a number of infections including those caused by sensitive strains of Pseudomonas aeruginosa. It can be synthesized starting with the Gould-Jacobs reaction of 3-chloro-4-fluoroaniline (28) and diethyl ethoxymethylenemalonate in an addition-elimination sequence leading to 29 which undergoes... 

Norfloxacin (41), the substance which triggered this avalanche of activity, has recently been introduced into clinical practice in the United States. Its synthesis parallels closely that of its N-methyl analogue, pefloxacin, except that the nucleophilic aromatic displacement reaction of 32 is carried out with mono-N-carboethoxypiperazine instead and the final step encompasses deblocking of this carbamoyl ester moiety [8]. 

CjjHjClFN 367-27-5) see Norfloxacin Pefloxacin 2-chloro-6-fluorobenzaldehyde (C7H4CIFO 387-45-1) see Flucloxacillin 2-chloro-6-lluorobenzaldehyde oxime (C7H5CIFNO 443-33-4) see Flucloxacillin... 

Oxolinic acid Pefloxacin Pipemidic acid Rosoxacin ... 

C2H5I 75-03-6) see Butibufen Cinoxacin Diethylstilbestrol Enoxacin Ethotoin Gallamine triethiodide Imiquimod Lomefloxacin Mosapride citrate Nalidixic acid Oxolinic acid Pefloxacin Pipemidic acid Tridihexethyl chloride Zaleplon... 

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... 

Nontyphoidal0 Trimethoprim-sulfamethoxazole DS twice daily ofloxacin 300 mg norfloxacin 400 mg or ciprofloxacin 500 mg twice daily x 5 days or ceftriaxone 2 g IV daily or cefotaxime 2 g IV three times daily x 5 days Enteric fever Ciprofloxacin 500 mg orally twice daily x 3-14 days (ofloxacin and pefloxacin equally efficacious)... 

The first members of the new fluoroquinolone class (such as norfloxacin (2a), enoxacin (5), pefloxacin (6), ciprofloxacin (2b) and ofloxacin (7)), are generally somewhat less active versus Gram-positive species than Gram-negative... 

The data on the adverse reactions of the fluoroquinolones which have received the most extensive clinical evaluation (ciprofloxacin, ofloxacin, pefloxacin, norfloxacin and enoxacin), involving about 30,000 patients, have been the subject of a review [54a], An important point noted in this review involves the difficulty in detecting an important severe adverse reaction if it is of relatively low frequency, until there has been a very large patient exposure (some examples are provided in which at least 150,000-300,000 exposures would be required to observe the importance of side-effects, resulting in an alert, which have been discovered with specific drugs). However, the majority of side-effects observed thus far with the fluoroquinolones have been minor,... 

The quinolones have been found to cause erosion of cartilage in the joints of immature animals [56]. This observation, which has been seen in several studies, has resulted in the contraindication of quinolones for the treatment of children. A study analyzing the risk-benefit situation for the use of pefloxacin in children (clinically, several adverse athralgic effects have been attributed to this agent) has appeared [57]. The underlying mechanism responsible for these effects has yet to be established, and the development of an agent which is safe for paediatric use would be a major advance in quinolone therapy. Some of the quinolones, such as enoxacin, have been shown to interfere with theophylline metabolism [58], and side-effects associated with this agent may be related to this property. 

A-56620) and (21 c) (difloxacin) were compared with the corresponding 1 -ethyl derivatives, norfloxacin and pefloxacin in mouse protection tests versus E. coli Juhl (Table 6.8). The two 7-(4-methylpiperazin-l-yl)quinolone derivatives, difloxacin and pefloxacin show enhanced oral activity relative to the 7-(piperazin-l-yl)quinolones, A-56620 and norfloxacin, respectively the absolute improvement in ED50 values in the 1-phenyl series is less dramatic. However, it should be noted that difloxacin, the more active agent in vivo, is 2 log2 dilutions less active in vitro. 

Based on the observation that pefloxacin (iV-methylnorfloxacin) exhibits enhanced in vivo activity upon oral administration (although it is less active in vitro) relative to norfloxacin, the same promoiety was investigated as an approach to blocking the secondary amine group, which seems to be associated with reduced oral absorption. Indeed, compound (78) was shown to produce about 5-fold higher serum levels of norfloxacin, after oral administration to mice than did the parent drug, itself. 

The 3-formyl analogues of norfloxacin, pefloxacin and ciprofloxacin, (82a-c) have also been shown to function as prodrugs of their respective parent... 

Palmoxirate sodium, 4 Pancuronium chloride, 69 Parkinson s disease, 20 Pefloxacin, 141,142,143 Pelrinone, 116 Pentiapine, 220 Pentizidone, 86 Pentopril, 128 Phenothiazine, 199 Picenadol, 108,109 Pinacidil, 102 Pinadoline, 202 Pipecuronium bromide, 70 Piperacillin, 179,188 Piquindone, 205 Piriprost, 160 Piritrexim, 169 Pirmagrel, 161 Pirogliride, 80 Piroxicam, 173 Piroximone, 94 Pivopril, 7... 

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