Imidazo- and triazoloquinolones as antibacterial agents. Synthesis and structure-activity relationships.
4,5-Disubstituted 6-cyclopropyl-6,9-dihydro-9-oxo-1H-imidazo (30-32) and triazolo[4,5-f]quinoline-8-carboxylic acids (33-35) were synthesized starting from 5,6-diaminoquinolones 25. The imidazoquinolones 30-32 were equal or superior to the corresponding triazoloquinolone analogues 33-35 in in vitro antibacterial activity. As for the C-5 substituents, a fluorine atom was the most favorable of the three groups, H, F, and Cl. Among the compounds prepared, 4-(cyclic amino)-5-fluoro-imidazoquinolones 31 a-d showed potent and well-balanced antibacterial activity against both gram-positive and gram-negative bacteria. Structure-activity relationships for the C-4 substituents (cyclic amino groups) were also examined in detail.
Fujita
M
M
Exploratory Research Laboratories, Dainippon Pharmaceutical Company, Osaka, Japan.
Egawa
H
H
Kataoka
M
M
Miyamoto
T
T
Nakano
J
J
Matsumoto
J
J
D000818:Animals; D000890:Anti-Infective Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D001419:Bacteria / Q000187:drug effects*; D006090:Gram-Negative Bacteria / Q000187:drug effects; D006094:Gram-Positive Bacteria / Q000187:drug effects; D007093:Imidazoles / Q000138:chemical synthesis* / Q000494:pharmacology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008826:Microbial Sensitivity Tests; D011552:Pseudomonas Infections / Q000188:drug therapy; D015363:Quinolones / Q000138:chemical synthesis* / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014230:Triazoles / Q000138:chemical synthesis* / Q000494:pharmacology
D000890:Anti-Infective Agents; D007093:Imidazoles; D015363:Quinolones; D014230:Triazoles