Synthesis and structure-activity relationships of novel arylfluoroquinolone antibacterial agents.
A series of novel arylfluoroquinolones has been prepared. These derivatives are characterized by having a fluorine atom at the 6-position, substituted amino groups at the 7-position, and substituted phenyl groups at the 1-position. Structure-activity relationship (SAR) studies indicate that the in vitro antibacterial potency is greatest when the 1-substituent is either p-fluorophenyl or p-hydroxyphenyl and the 7-substituent is either 1-piperazinyl, 4-methyl-1-piperazinyl, or 3-amino-1-pyrrolidinyl. The electronic and spatial properties of the 1-substituent, as well as the steric bulk, play important roles in the antimicrobial potency in this class of antibacterials. As a result of this study, compounds 45 and 41 were found to possess excellent in vitro potency and in vivo efficacy.
D000150:Acinetobacter / Q000187:drug effects; D000818:Animals; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000494:pharmacology / Q000627:therapeutic use*; D000890:Anti-Infective Agents; D001424:Bacterial Infections / Q000188:drug therapy; D055598:Chemical Phenomena; D002621:Chemistry; D002939:Ciprofloxacin / Q000031:analogs & derivatives*; D004754:Enterobacter / Q000187:drug effects; D004926:Escherichia coli / Q000187:drug effects; D005260:Female; D005461:Fluorine / Q000138:chemical synthesis / Q000494:pharmacology; D024841:Fluoroquinolones; D007711:Klebsiella pneumoniae / Q000187:drug effects; D051379:Mice; D009643:Norfloxacin / Q000031:analogs & derivatives / Q000494:pharmacology; D015366:Pefloxacin; D010879:Piperazines / Q000494:pharmacology / Q000627:therapeutic use; D011550:Pseudomonas aeruginosa / Q000187:drug effects; D011804:Quinolines / Q000138:chemical synthesis / Q000494:pharmacology* / Q000627:therapeutic use; D013210:Staphylococcus / Q000187:drug effects; D013291:Streptococcus / Q000187:drug effects; D013329:Structure-Activity Relationship
D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents; D024841:Fluoroquinolones; D010879:Piperazines; D011804:Quinolines; D005461:Fluorine; D015366:Pefloxacin; D002939:Ciprofloxacin; C047225:difloxacin; C037219:quinoline; D009643:Norfloxacin; C047224:sarafloxacin