Norfloxacin

T rade Name Manufacturer Country Year introduced 

Legerlotz, H. U.S. Patent 2,312,916 March 2, 1943 assigned to Ciba Pharmaceutical Products Inc. 

Chemical Name 1-Ethyl-6-fluoro-1,4-dihydro-4-oxo-7-(1 -piperazinyl)-3-qulnolinecar-boxylic acid 

7-Chloro-1 -ethyl-6-fluoro-4-0X0-1,4-dihydroquInoline-3-carboxylIc acid Piperazine 

36 g (0.134 mol) of 7-chloro-1 -ethyl-6-fluoro4-oxo-1,4-dihydroquinollne-3-carboxylle acid, 46 g of piperazine and 210 cm of pyridine were heated under reflux for 6 hours, while stirring. After the starting material had dissolved,a precipitate appeared after heating for about 2 hours 30 minutes. The ma or part of the solvent was removed by concentration in vacuo (15 mm Hg 100°C). in order to remove the pyridine as completely as possible, the residue was taken up in 200 cm of water and the concentration in vacuo was repeated. 

The residue, resuspended in 150 cm of water, was stirred. 150 cm of 2 N NaOH were added thereto. The solution, which was slightly turbid, was treated with 5 g of animal charcoal and stirred for 30 minutes. After filtration, the pH was brought to 7.2 by adding acetic acid, while stirring. The precipitate was filtered off, washed with water and dissolved in 250 cm of a 10% aqueous acetic acid. The acid solution (pH 4.4) was filtered and then brought to pH 7.2 by gradually added 2N NaOH. 

Steric parameters include the Taft Es value and the Verloop 

In the 1960s various heterocycles, anilides, and phenyl compounds substituted with urea or carbamate were known to exhibit herbicidal activity by interfering with photosynthesis in plant cells. Draber and co-workers at Bayer AG (Leverkusen, Federal Republic of Germany) investigated a new series of 

4- amino-l,2,4-triazin-5-ones 4. The Hansch approach was still relatively new at the time. A series of 22 compounds was investigated with R3 being an 

5- alkyl, O-alkyl, or N-alkyl group and Rg being a normal or branched alkyl group or a phenyl group. -Octanol/water partition coefficients were deter- 

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The 8-position of the quinolone nucleus can often be advantageously substituted by fluorine (58) or chlorine (59) to give compounds with improved antibacterial potency over hydrogen in this position. With 1,8-naphthyridines, activity is reported to be approximately equivalent to the quinolone bearing a hydrogen in this position (60). As an example of this, see the data for norfloxacin (8) and enoxacin (7) in Table 2. 

DETERMINATION OF DNA BY ITS ENHANCEMENT EFFECT ON THE FLUORESCENCE OF Tb -NORFLOXACIN COMPLEX... 

Norfloxacin (1, R = C2H5, R = H), a typical example, exhibits broad-spectrum activity and is useful in the treatment of upper respiratory tract and urinary infections [7] Lomefloxacin (2), a very recent introduction, is a third-generation product that, given once daily, is especially useful against pathogens resistant to cephalosponns, penicillins, and aminoglycosides [4] Floxacillin (J) is a stable, orally active antibacterial with improved activity over thenonfluonnated product (cloxacillin) [5]... 

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]. 

The fluoroquinolones are used in the treatment of infections caused by susceptible microorganisms. The fluoroquinolones are effective in the treatment of infections caused by gram-positive and gram-negative microorganisms. They are primarily used in the treatment of susceptible microorganisms in lower respiratory infections, infections of the skin, urinary tract infections, and sexually transmitted diseases. Ciprofloxacin, norfloxacin, and ofloxacin are available in ophthalmic forms for infections in the eyes. 

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... 

C2H5Br 74-96-4) see Actinoquinol Amobarbital Benzilonium bromide Cyclobarbital Edrophonium chloride Heptabarb Mephenytoin Methylphenobarbital Norfloxacin Oxitropium bromide Phenobarbital Remoxipride Secbutabaibital Valdetamide ethyl bromoacetate... 

Yang M and Santerre JP. Utihzation of quinolone drugs as monomers Characterization of the synthesis reaction products for poly(norfloxacin diisocyanatododecane polycaprolactone). Biomacromolecules, 2001, 2, 134-141. 

Over 10000 quinolone antibacterial agents have now been synthesized. Nalidixic acid is regarded as the progenitor of the new quinolones. It has been used for several years as a clinically important drug in the treatment of urinary tract infections. Since its clinical introduction, other 4-quinolone antibacterials have been synthesized, some of which show considerably greater antibacterial potency. Furthermore, this means that many types of bacteria not susceptible to nahdixic acid therapy m be sensihve to the newer derivahves. The most important development was the introduction of a fluorine substituent at C-6, which led to a considerable increase in potency and spectrum of activity compared with nalidixic add. These second-generation quinolones are known as fluoroquinolones, examples of which are ciprofloxacin and norfloxacin (Fig. 5.19). 

Traveller s diarrhoea may be eaused by one of many gastrointestinal pathogens (Table 6.4). However, enterotoxigenic Escherichia coli is the most common pathogen. Whilst it is generally short-lived, traveller s diarrhoea can seriously mar a brief period abroad, be it for holiday or business purposes. Although not universally accepted, the use of short-course co-trimoxazole or quinolone such as norfloxacin can abbreviate an attack in patients with severe disease. 

Chloral hydrate Chloramphenicol Cimetidine Ciprofloxacin Clofibrate Danazol Disulfiram Doxycycline Erythromycin Fenofibrate Fluconazole Fluorouracil Fluoxetine Fluvoxamine Gemfibrozil Influenza vaccine Isoniazid Itraconazole Fovastatin Metronidazole Miconazole Moxalactam Neomycin Norfloxacin Ofloxacin Omeprazole Phenylbutazone Piroxicam Propafenone Propoyxphene Quinidine Sertraline Sulfamethoxazole Sulfinpyrazone Tamoxifen Testosterone Vitamin E Zafirlukast... 

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