A quinolones

Several promising antibacterial compounds are available and may be considered for use in U.S. aquaculture. In addition to sarafloxacin, other quinolones, flumequine and oxolinic acid, are already registered in Europe. However, resistance to both of these compounds developed in bacteria in just a few years (20). Enrofloxacin, [95106-60-6], C22H22FN2O2, a quinolone product of Bayer A.G. (Germany), is also a candidate for aquaculture registration in Europe and may be considered for registration in the United States. 

The facile a,a diacylation with arylisocyanates has been applied to the synthesis of polymers (434-436), while the monoacylation products have been used as intermediates for the synthesis of substituted a-quinolones and their sulfur analogs (437). 

The structure of the product of the Reimer-Tiemann reaction of 1,2,3-trimethylindole (24) has been confirmed as 3-dichloromethyl-1,3-dimethyl-2-methyleneindoline (25) by spectroscopy and oxidation to the iV -methyloxindole when the dichlorocarbene was generated under neutral conditions a ring-expanded product, 3-chloro-1,4-dimethyl-2-methylene-1,2-dihydroquinoline (26) could be isolated and oxidized to the corresponding a-quinolone. These reactions presumably proceed by mechanisms similar to those discussed for 2,3-di-... 

Five different types of reactors, including tube reactors, static mixers and a microstructured reactor, were tested for the synthesis of an intermediate to 3deld a quinolone antibiotic drug, named Gemifloxacin (FACTIVE ) [13,14]. 

Zwitterionic character is notable in several therapeutic area series, e.g. in angiotensin-converhng enzyme inhibitors, quinolone anhbacterials and thrombin inhibitors. The aqueous solubiUty measurement of zwitterions is very pH dependent as might be expected. The relationship of aqueous solubiUty to ionization state is extraordinarily complex if the zwitterion is of the type capable of an equi-Ubrium between true zwitterion and formally neutral forms (e.g. as in a quinolone antibacterial). For these types of complex equilibria, salt effects on solubility may be unexpectedly large, e.g. solubility unexpectedly may track with the chaotropic character of the salt... 

Regioselective hydrolysis of the diester 27 gave the 1,3-thiazetidine 28 where the thiazetidine ring is fused to a quinolone nucleus <99CPB1765>. Derivatives of the tricyclic system, e.g. 29, showed activity against gram-positive bacteria including quinolone-resistant MRS A <99H(51)2915>. 

Completion of the antimicrobial course with oral forms of a quinolone plus metronidazole,... 

Patients allergic to /3-lactams should receive a quinolone. Persons unable to tolerate a /3-lactam (penicillin or cephalosporin) or a quinolone should receive spectinomycin. 

There is an increased risk of hyperkalaemia when ciclosporin is given with Coversyl, which contains perindopril, an angiotensin-converting enzyme inhibitor. Risk of nephrotoxicity associated with ciclosporin is increased with concomitant use with quinolones. Ciproxin contains ciprofloxacin, which is a quinolone. Tenormin contains atenolol, which is a beta-adrenoceptor blocker and there are no interactions between these agents and ciclosporin. 

Cefalexin is a first-generation cephalosporin and therefore an alternative preparation would be Zinnat tablets, which contains cefuroxime, a second-generation cephalosporin. A penicillin such as Augmentin, which contains co-amoxiclav, can be an appropriate alternative since it provides a very similar spectrum of activity. Klaricid contains clarithromycin, which is a macrolide. Utinor contains norfloxacin, which is a quinolone that is effective in uncomplicated urinary-tract infections. Rocephin contains ceftriaxone, which is a third-generation cephalosporin that is available for parenteral administration only. 

Treatment should be guided by the local or hospital resistance patterns. Extensive use of a quinolone for selective decontamination will increase the incidence of quinolone-resistant gram-negative pathogens. Alternative regimens for gut decontamination are oral colistin with an oral aminoglycoside such as neomycin. 

Family members and close contacts of patients diagnosed with invasive meningococcal disease are given oral rifampicin 600 mg twice daily for 2 days or a single dose of a quinolone e.g. ciprofloxaein 500 mg. 

C) Initiate a quinolone like levofloxacin with broad-spectrum coverage for UTIs... 

Mechanism of Action A quinolone that inhibits the enzyme DNAgyrase in susceptible microorganisms, interfering with bacterial cell replication and repair. Therapeutic Effect Bactericidal. 

Mecfianism of Action A quinolone-methanol compound structurally similar to quinine that destroys the asexual blood forms of malarial pafhogens, Plasmodium falciparum, P. vivax, P. malariae, P. ovale. Therapeutic Effect Inhibifs parasite growth. Pharmacokinetics Well absorbed from fhe gasfroinfesfinal (GI) tract. Protein binding 98%. Widely distributed, including cerebrospinal fluid (CSF). Metabolized in liver. Primarily excreted in urine. Half-life 21-22 days. 

The lead compound for this series, nalidixic acid (38-6), which is acmally a naphthyridine rather than a quinolone, was first introduced over four decades ago. That compound for many years found its niche as a rather effective drug for the treatment of urinary tract infection. The rediscovery of the general stmcmral class in the early 1980s hinged on the discovery of the importance of fluorine at the 6 position and basic nitrogen at position 7. This renewed research led to the development of a very large series of potent broad spectmm antibiotics. This is reflected in the fact that more than 20 quinolone antibiotics have been granted U.S. nonproprietary names. 

Very much the same strategy is used to synthesize a quinolone that contains an additional fused ring. This agent features a broad-spectrum antibacterial activity in spite of the lack of a nitrogen substituent at position 7. It is of note in this case... 

The hydroxyquinoline (39-2) provides the starting material for a quinolone that incorporates a hydrazine function. Reaction of (39-2) with 2,4-dintrophenyl O-hydroxylamine ether (41-1) in the presence of potassium carbonate leads to a scission of the weak N-O hydroxylamine bond by the transient anion from the quinolone the excellent leaving character of 2,4-dinitrophenoxide adds the driving force for the overall reaction, resulting in alkylation on nitrogen to form the hydrazine (41-2). The primary amine is then converted to the formamide (41-3) by reaction with the mixed acetic-formic anhydride. Alkylation of that intermediate with methyl iodide followed by removal of the formamide affords the monomethylated derivative (41-4). Chlorine at the 7 position is then displaced by A-methylpiperazine and the product saponified. There is thus obtained amifloxacin (41-6) [48]. 

The product from the formal replacement of the benzimidazolone function in itasetron (57-6, Chapter 10) by a quinolone has been reported to display much the same serotonin antagonists activity of the former. In the absence of a specific reference to the synthesis, the starting quinolone is speculatively formed by reaction of cyclo-hexylaniline (50-1) with EMME to produce the enamide (50-2) from displacement... 

A closely related reaction between 1 -arylpyrrolidine-2-thiones 96 and diethyl bromoma-lonate97 under Reformatsky conditions afforded l-arylpyrrolidin-2-ylidenemalonates 98, which, upon polyphosphoric acid (PPA) induced cyclization, opened a route to pyrrolo[l, 2-a] quinolones 99145, tricyclic analogues of quinolone antibiotics (equation 58). 

American Home Products has patented molecules ranging from substituted quinoline, piperidine, and naphthpyridine compounds as immunomodulators. Ciprofloxacin, a quinolone antibiotic, reduced the extracellular IL-1 activity in human monocytes and delayed the peak production of IL-la IL-(3 by 24 h and decreased total IL-113 production, but did not change total IL-la production [75,76]. 

Quinolone carboxylic acid antibacterials are synthetic compounds whose basic nuclear structure includes a quinolone ring and a carboxylic acid group. Fluoroquinolones are second-generation quinolones that contain in their molecule a fluorine and a piperazine ring. Quinolones are amphoteric compounds slightly soluble in polar solvents such as water, and insoluble in nonpolar solvents such as benzene and hexane. Most of these drugs are fluorescent and are quite stable in aqueous solution toward light, except miloxacin, which is reported to be unstable. 

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