Quinolones, evolution

The synthesis and antibacterial properties of norfloxacin (2a) were described in 1980 [65]. In this key paper in the evolution of quinolone antibacterial agents, a series of 6,7,8-polysubstituted-l-ethyl-l,4-dihydro-4-oxoquinoline-3-carb-oxylic acids (13) was synthesized, employing previously developed quantitative structure-activity relationships (QSAR) for the corresponding 6-, 7- and 8-monosubstituted derivatives versus Escherichia coli. The QSAR analysis... 

This article reveals the reflections of the author on the chemical evolution of moxifloxacin. During the course of Bayer s quinolone research project that resulted in the development of moxifloxacin, numerous compounds were synthesized, and attempts were made to modify almost every quinolone substituent in a variety of ways in order to meet the goals described herein. Some of these efforts were successful, while others were not. This chapter does not attempt to describe this project in its entirety. Instead, for the sake of brevity and simplicity, many areas of this complex and difficult project have been excluded or substantially simplified in order to focus on those areas of the Bayer project which, in retrospect, were most important to the development of moxifloxacin. 

The evolution of the quinolones, which began with nalidixic acid and has produced the modem fluoroquinones moxifloxacin, gatifloxacin and gemifloxacin, was based not only on modifications of the basic quinolone structure but also on the development of new cyclic amines for the 7-position. The cyclopropyl radical, which was introduced for the first time in ciprofloxacin, remains the most effective substituent for the 1-position. Moxifloxacin is an 8-methoxy fluoroquinolone with a novel enantiomerically pure S,S-2,8-diazabicyclo[4.3.0]non-8-yl radical in the 7-position. 

Both quinoline and isoquinoline can be directly hydroxylated with potassium hydroxide at high temperature with the evolution of hydrogen. 2-Quinolone ( carbostyril ) and 1-isoquinolone ( isocarbostyril ) are the isolated products. 

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