Antibacterial activity and pharmacokinetics of four new 7-azetidinyl fluoroquinolones

The activity of E-4535, E-4534, E-4528, and E-4527, four new 7-azetidinyl-6-fluoroquinolones, was studied to evaluate the role played by the C-2' and C-3' substitutions of the azetidinyl group, together with a C-8 fluorine atom. In general, like other 6,8-difluoroquinolones, E-4534 and E-4527 showed higher levels of activity than the corresponding monofluorinated derivatives, E-4535 and E-4528. E-4535 and E-4534, having a 7-(2-methyl-3-aminoazetidinyl) substituent, demonstrated higher levels of activity in vitro than their corresponding structural analogs, E-4528 and E-4527, distinguished by a 3-methyl-3-methylaminoazetidinyl group at position 7 of the quinolone nucleus. In consequence, E-4534 was the most potent of the new agents tested.