Synthesis of 7-thio-substituted 4-oxoquinoline-3-carboxylic acids with antibacterial activity.
A series of C-7 thio-substituted 1-cyclopropyl-1,4-dihydro-4-oxoquinoline-3-carboxylic acids were prepared and tested for their antibacterial activity. Structure-activity relationships associated with the C-5 and C-7 substituents were discussed. Among the C-7 substituents including alkylthio, arylthio, heteroarylthio, and cyclic aminothio groups, a 2-aminoethylthio group was the best for enhancing in vitro antibacterial activity. The C-5 variants increased activity in the order OH less than F less than H less than NH2. Of compounds prepared in this work, 5-amino-7-(2-aminoethyl)thio-1-cyclopropyl-6,8-difluoro-1,4-dihydro-4 -oxo-quinoline-3-carboxylic acid (18) was the most active.
Nishimura
Y
Y
Research Laboratories, Dainippon Pharmacetical Co., Ltd., Osaka, Japan.
Hirose
T
T
Okada
H
H
Shibamori
K
K
Nakano
J
J
Matsumoto
J
J
D042462:4-Quinolones; D000890:Anti-Infective Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D004353:Drug Evaluation, Preclinical; D004926:Escherichia coli / Q000187:drug effects; D024841:Fluoroquinolones; D011550:Pseudomonas aeruginosa / Q000187:drug effects; D013211:Staphylococcus aureus / Q000187:drug effects; D013329:Structure-Activity Relationship; D013455:Sulfur
D042462:4-Quinolones; D000890:Anti-Infective Agents; D024841:Fluoroquinolones; D013455:Sulfur; C061363:sparfloxacin