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

Authors:
  • PCP. Di Cesare
    P. Di Cesare
  • MEM. Essiz
    M. Essiz
  • JJJ. P. Jacquet
    J. P. Jacquet
  • BLB. Ledoussal
    B. Ledoussal
  • PRP. Remuzon
    P. Remuzon
  • RKR. E. Kessler
    R. E. Kessler
  • JFJ. Fung-Tomc
    J. Fung-Tomc
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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.