.7 - Substituted Pyrrolidinyl And 5 - Amino-8 - Methoxy Quinolone Compound Synthesis And Antibacterial Activity

Quinolone antibacterial agents have emerged as one of the dominant classes of chemotherapeutic drugs for the treatment of various bacterial infections because of their broad-spectrum, potent and low toxicity. However, most of the quinolones currently on the market or under development have only moderate activity against many Gram-positive pathogens, Mycoplasma and Chlamydia. In order to find novel quinolones with strong activity against these pathogens, we have focused our attention on the modification of the C-7 basic group, C-5 and C-8 positions of the quinolone.We noticed that quinolone that has an amino group on the pyrrolidine ring is essential for good in vitro (especially Gram-positive) activity, but it has low water-solubility. In 1987, Uno et al reported that 3-hydroxypyrrolidine quinolones showed more active antibacterial activities in vivo than norfloxacin. In 1998, Fujita et al reported that 2-aminomethylpyrrolidine quinolones had the same in vitro antibacterial activities against Gram-positive and Gram-negative bacteria with the Spafloxcin as the comparison. Then, our interest was directed to the synthesis of 2-aminomethyl-4-hydroxypyrrolidine quinolones and their antibacterial activities. We introduced hydroxy, methyloxy or methyloxime group into the C₄-position to increase their water-solubility and an aminomethyl or methylaminomethyl substituent into the C₂-position of the pyrrolidine ring. Six series of quinolone analogues were synthesized.In the other hand, an amino group on the C₅-position of the quinolone...