Studies on 6-aminoquinolones: synthesis and antibacterial evaluation of 6-amino-8-methylquinolones.
The 6-aminoquinolone had previously been identified as a new class of quinolone antibacterial agents. To continue our structure-activity relationship (SAR) study in this series, novel 6-amino-8-methylquinolone derivatives have now been synthesized and evaluated for in vitro antibacterial activity. We have shown that the coupled presence of a methyl group at the C-8 position with an amino group at C-6 is effective for enhancing antibacterial activity, particularly against Gram-positive bacteria. The SARs associated with the N-1, C-6, and C-7 are discussed. The 1,2,3,4-tetrahydroisoquinolinyl derivative 19v showed the highest antibacterial activity with MIC values on Gram-positive bacteria superior to that of ciprofloxacin, especially against Staphylococcus aureus strains, including those strains which are methicillin-and ciprofloxacin-resistant.
Cecchetti
V
V
Istituto di Chimica Farmaceutica e Tecnica Farmaceutica, Università di Perugia, Italy.
Fravolini
A
A
Lorenzini
M C
MC
Tabarrini
O
O
Terni
P
P
Xin
T
T
D000818:Animals; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000494:pharmacology* / Q000627:therapeutic use; D005260:Female; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D051379:Mice; D015363:Quinolones / Q000138:chemical synthesis* / Q000494:pharmacology* / Q000627:therapeutic use; D018805:Sepsis / Q000188:drug therapy / Q000382:microbiology; D013211:Staphylococcus aureus / Q000187:drug effects; D013329:Structure-Activity Relationship
D000900:Anti-Bacterial Agents; D015363:Quinolones