Synthesis and biological activity of 5-alkyl-1,7,8-trisubstituted-6-fluoroquinoline-3-carboxylic acids.
A series of 5-alkyl-1,7,8-trisubstituted-6-fluoro-1,4-dihydro-4-oxo-3- quinolinecarboxylic acids was prepared and evaluated for in vitro and in vivo antibacterial activity. When compared to the 5-hydrogen analogues, the presence of the 5-methyl group enhanced in vitro potency for those compounds containing a cyclopropyl moiety at N1 but decreased potency for those containing an ethyl group at N1. Replacing the 5-methyl with a 5-ethyl significantly reduced the efficacy. In general, the 5-methyl and 5-hydrogen analogues were equipotent in vivo. Several of the 5-methyl-1-cyclopropylquinolones displayed excellent in vitro and in vivo activity, warranting further development.
Hagen
S E
SE
Parke-Davis Pharmaceutical Research Division, Warner-Lambert Company, Ann Arbor, Michigan 48105.
Domagala
J M
JM
Heifetz
C L
CL
Johnson
J
J
D042462:4-Quinolones; D000890:Anti-Infective Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D055598:Chemical Phenomena; D002621:Chemistry; D006090:Gram-Negative Bacteria / Q000187:drug effects*; D006094:Gram-Positive Bacteria / Q000187:drug effects*; D008745:Methylation; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D013329:Structure-Activity Relationship
D042462:4-Quinolones; D000890:Anti-Infective Agents