N <sub> 1 </ Sub> - (2 - Fluoro-5 - Pyridine Base) And 7 - (7 - (aminomethyl) -5 - Diazaspiro [2,4] Heptane - 5 - Yl) Fluoroquinolones Synthesis And Antibacterial Activity

Fluoroquinolone antibacterial agents have emerged as one of the dominant classes of chemotherapeutic drugs for the treatment of various bacterial infections. However, most of the fluoroquinolones only have moderate activity against Gram-positive pathogens, Mycoplasma and Chlamydia. In order to find novel fluoroquinolones with greater antibacterial activity against these pathogens, based on the relationship of the structure-activity and the mode of fluoroquinolones, we had focused our attention on the modification of N₁-group and C-7 basic group of fluoroquinolone.1) Considering that the fluoroquinolones with N₁-(2,4-difluorophenyl) posses great antibacterial activity against Gram-positive organism, we had prepared a series of the fluoroquinolones bearing an isosterism of 2,4-difluorophenyl, a hydrophilic group 2-fluoro-5-pyridyl, at N₁-position.2) Compared with piperazinyl analogs, introducing pyrrolidine derivativatives to the flouroquinolones resulted in a dramatic improvement of in vitro Gram-positive organism and considering alkylation at the 4-postion of 3-amino- or 3-aminomethylpyrrolidine produced novel quinolones with increased oral activity, a new pyrrolidine derivative, which bares two-alkyls substituent in the 4-position and an aminomethyl substituent in the 3-position of the pyrrolidine ring, 7-aminomethyl-5-azaspiro-[2,4]heptane, had been synthesized and coupled with various quinolonecarboxylic acids to produce 8 of new fluorquinolone antibacterial agents.