Norfloxacin analogs

A. Analogy by ring opening B. Morphinic analgesics C. Norfloxacin analogs... 

Norfloxacin transformation has been demonstrated by P. guepini [30] and T. viride [32]. In the first case, the metabolites identified included /V-acetyl norfloxacin as the major intermediate, desethylene-Af-acetylnorfloxacin, /V-formy I norfloxacin, and 7-amino-l-ethyl-6-fluoro-4-oxo-l,4-dihydroquinoline-3-carboxylic acid. For T. viride, 4-hydroxy-3-oxo-4-vinylcyclopent-l-enyl norfloxacin was elucidated as an intermediate. In both reports, the intermediates were analogous... 

The quinolone class of drugs were discovered in the 1960s when Lesher et al. isolated nalidixic acid as a by-product of chloroquine synthesis (2). More than a thousand quinolones and analogs have since been synthesized and evaluated in an attempt to reduce toxicity and increase antimicrobial potency. The attachment of a fluorine to C-6 and a piperazine or methylpiperazine to C-7 has led to more active agents such as norfloxacin, ciprofloxacin, ofloxacin and lomefloxacin (3). 

Quinolone analogs commercially available in the United States are lomefloxacin (Maxaquin), norfloxacin (Noroxin), ciprofloxacin (Cipro), enoxacin (Penetrex) and ofloxacin (Floxin). Agents such as enoxacin, pefloxacin and ofloxacin are also available in Europe. Other agents such as fleroxacin are expected to be available soon (4). 

FIGURE 6.5 The striking analogy between the vasodilator drug flosequinan and the quinolone antibiotic norfloxacin. 

Since the development in 1980 of norfloxacin as a nsefnl antibacterial agent, a large nnmber of analogs have been synthesized. Among them, the conjnnctive approach led to highly potent tetracyclic analogs (Fignre 16.39). ... 

Fluorocinnoline derivatives have recently been reported and aza-analogs of norfloxacin prepared (Fig. 24). Comparison of the activity of both compounds has indicated that the introduction of an additional nitrogen atom at position 2 of the quinolone ring causes a considerable decrease in activity. Among the other... 

Synthesis and antimicrobial activity of 3-formyl analogs of norfloxacin, ciprofloxacin, and pefloxacin have been reported [93]. These studies have shown definitive evidence that the 3-formyl analogs of quinolones function as prodrugs and are oxidized in vivo to carboxylic acids. The higher bioavailability of formyl derivatives may be due to a change in physical and chemical properties by the lack of their amphoteric nature, compared to the parent zwitterionic compounds. 

Although this first major, widespread effort at SBDD was a disappointment, the situation looked better on the QSAR front. In Japan, Koga " " employed classical (Hansch-type) QSAR while discovering the antibacterial agent norfloxacin around 1982. Norfloxacin was the first of the third-generation analogs of nalidixic... 

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