6-AMINOQUINOLONES - A NEW CLASS OF QUINOLONE ANTIBACTERIALS

A series of quinolone- and 1,8-naphthyridone-3-carboxylic acids, desig ned by previous QSAR studies and characterized by an amino group at th e C-6 position instead of the usual fluorine atom, were synthesized fo r the first time and evaluated for in vitro antibacterial activity. Al l of the synthesized compounds maintain good activity against Gram-neg ative bacteria (Pseudomonas aeruginosa excluded), and those compounds having a thiomorpholine group as the C-7 substituent also have good ac tivity against Gram-positive bacteria. Some aspects of structure-activ ity relationships associated with the C-1, C-5, C-7, and C-8 substitue nts are also discussed. Derivatives 18g and 38g displayed the best act ivity with geometric mean MICs of 0.45 and 0.66-0.76 mu g/mL against G ram-negative and Gram-positive bacteria, respectively. This antimicrob ial activity reflects their ability to inhibit bacterial DNA-gyrase. T he results of this study show that, while the C-6 fluorine is still th e preferred substituent, good activity can still be obtained by replac ing it with an amino group.