title: Fluoronaphthyridines as antibacterial agents. 4. Synthesis and structure-activity relationships of 5-substituted-6-fluoro-7-(cycloalkylamino)-1,4-dihydro-4-oxo-1,8- naphthyridine-3-carboxylic acids.
abstract: A series of 5-substituted-6-fluoro-7-(cycloalkylamino)-1,4-dihydro-4-oxo-1,8- naphthyridine-3-carboxylic acids have been prepared and tested for their in vitro and in vivo antibacterial activities. The 5-methyl group gave better in vitro activity with the 1-cyclopropyl appendage, but poorer activity with the 1-tert-butyl moiety. With the 1-(2,4-difluorophenyl) substitution, the influence of the 7-cycloalkylamino group was determinant: a (3S)-3-amino-pyrrolidine was shown to enhance greatly the in vitro and in vivo activity of the 5-methyl derivative. Compound 33 (BMY 43748) was selected as a promising candidate for an improved therapeutic agent.
authors.affiliation: Bristol-Myers Squibb Pharmaceutical Research Institute, Marne-La-Vallée, France.
authors.forename: D
authors.initials: D
authors.lastname: Bouzard
authors.forename: P
authors.initials: P
authors.lastname: Di Cesare
authors.forename: M
authors.initials: M
authors.lastname: Essiz
authors.forename: J P
authors.initials: JP
authors.lastname: Jacquet
authors.forename: B
authors.initials: B
authors.lastname: Ledoussal
authors.forename: P
authors.initials: P
authors.lastname: Remuzon
authors.forename: R E
authors.initials: RE
authors.lastname: Kessler
authors.forename: J
authors.initials: J
authors.lastname: Fung-Tomc
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology; D001419:Bacteria / Q000187:drug effects*; D051379:Mice; D009287:Naphthyridines / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D000900:Anti-Bacterial Agents; D009287:Naphthyridines