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.

E-4695, a new C-7 azetidinyl fluoronaphthyridine with enhanced activity against gram-positive and anaerobic pathogens.

E-4695, (-)-7-[3-(R)-amino-2-(S)-methyl-1-azetidinyl]-1-cyclopropyl-1,4- dihydro-6-fluoro-4-oxo-1,8-naphthyridine-3-carboxylic acid, is a new fluorinated naphthyridine with an azetidine moiety. The MICs of E-4695 at which 90% of the isolates were inhibited (MIC90s) were 0.06 to 0.

In vitro activity of E-4868, a new fluoroquinolone with a 7-azetidin ring, compared with ciprofloxacin, ofloxacin and fleroxacin.

E-4868, (-)-7[3-(R)-amino-2-(S)-methyl-1-azetidinyl]-1-(2,4- difluorophenyl)-1,4-dihydro-6-fluoro-4-oxo-3-quinolinecarboxylic acid, is a new fluoroquinolone with a 7-azetidin ring substituent. The in vitro activity against clinical isolates was compared with that of ciprofloxacin, ofloxacin and fleroxacin. In general, activity of E-4868 against aerobic and facultative anaerobic Gram-negative bacilli was equal to or slightly less active than ciprofloxacin with the exception of Morganella morganii and Proteus spp.

In vitro and in vivo antibacterial activities of E-4868, a new fluoroquinolone with a 7-azetidin ring substituent.

E-4868, (-)-7-[3-(R)-amino-2-(S)-methyl-1-azetidinyl]-1-(2,4- difluorophenyl)-1,4-dihydro-6-fluoro-4-oxo-3-quinolinecarboxylic acid, is a new fluoroquinolone with an azetidine moiety at the 7 position. The in vitro activity of E-4868 has been compared with those of ciprofloxacin, ofloxacin, and fleroxacin, while the activity of ciprofloxacin was used as reference for in vivo studies. The MICs of E-4868 for 90% of the isolates tested (MIC90s) were 0.

Comparative in vitro and in vivo activities of six new monofluoroquinolone and difluoroquinolone 3-carboxylic acids with a 7-azetidin ring substituent.

E-4502, E-4501, E-4500, E-4480, E-4474, and E-4441 are new monofluorinated or difluorinated quinolone agents that are chemically characterized by the presence of an azetidin ring, with different C'-3 substituents, at position 7 of the molecular structure. The MICs of the difluorinated compounds E-4501, E-4474, and E-4441 for 90% of isolates were 0.06 to 1, 0.

Antimicrobial activity of E-4441, a representative azetidine quinolone.

E-4441 is a third-generation difluoroquinolone characterized by the presence in position 7 of an azetidine ring, disubstituted in position 3 by amine and methyl groups. E-4322 is another difluoroquinolone which differs from the former in having a 3-acetidinol substitution in position 7. E-4441 shows satisfactory levels of activity, both in vitro and in vivo, its activity against G(+) aerobic bacteria and anaerobic bacteria being generally notable.

Activity of E-3846, a new fluoroquinolone, in vitro and in experimental cystitis and pyelonephritis in rats.

The in vitro antibacterial activity of E-3846, a new fluoroquinolone carboxylic acid derivative with a pyrrol ring substituent at position 7, was evaluated in comparison with norfloxacin and ciprofloxacin. E-3846 was more active than the reference quinolones against Staphylococcus species, including methicillin-resistant strains. E-3846 was similar to ciprofloxacin and more active than norfloxacin against Streptococcus (Enterococcus) faecalis.

In vitro antibacterial activity of E-3604, a new 6-fluoroquinolone, on clinical isolates.

From a series of pyrrol-containing antibacterial agents, E-3604 was selected for development and compared with nalidixic acid, norfloxacin and ciprofloxacin against strains of clinical isolates. The in vitro activity of E-3604 was greater than that of nalidixic acid, similar to that of norfloxacin and lower than that of ciprofloxacin, except in the case of Staphylococcus where E-3604 showed the best in vitro activity of all the studied compounds, with a MIC range of 0.25-0.

In vitro antibacterial activity of irloxacin (E-3432) on clinical isolates.

Irloxacin (E-3432) is a new quinolone derivative. In this study, the activity of irloxacin was compared with that of nalidixic acid, norfloxacin and ciprofloxacin against strains of clinical isolates. Irloxacin showed greater in vitro activity than nalidixic acid, similar activity to norfloxacin and lower activity than ciprofloxacin.