title: Antibacterial activity and pharmacokinetics of four new 7-azetidinyl fluoroquinolones.
abstract: 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.
authors.affiliation: Department of Microbiology, Laboratorios Dr. Esteve, Barcelona, Spain.
authors.forename: R
authors.initials: R
authors.lastname: Coll
authors.forename: D
authors.initials: D
authors.lastname: Gargallo-Viola
authors.forename: E
authors.initials: E
authors.lastname: Tudela
authors.forename: M A
authors.initials: MA
authors.lastname: Xicota
authors.forename: S
authors.initials: S
authors.lastname: Llovera
authors.forename: J
authors.initials: J
authors.lastname: Guinea
mesh_terms: D000818:Animals; D000890:Anti-Infective Agents / Q000493:pharmacokinetics* / Q000494:pharmacology*; D001424:Bacterial Infections / Q000188:drug therapy / Q000378:metabolism; D024841:Fluoroquinolones; D006092:Gram-Negative Facultatively Anaerobic Rods / Q000187:drug effects*; D006095:Gram-Positive Cocci / Q000187:drug effects*; D051379:Mice; D008826:Microbial Sensitivity Tests; D013329:Structure-Activity Relationship
chemical_list: D000890:Anti-Infective Agents; D024841:Fluoroquinolones