title: Synthesis and biological properties of substituted 1,4-dihydro-5-methyl-4-oxo-3-quinolinecarboxylic acids.
abstract: A series of substituted 1-cyclopropyl-6-fluoro-1, 4-dihydro-5-methyl-4-oxo-3-quinoline carboxylic acids was synthesized and tested for their in vitro and in vivo antibacterial activity. The introduction of a methyl group at the 5-position of quinoline nucleus enhanced characteristically the antibacterial activity against Gram-positive bacteria, including Streptococcus pneumoniae, which is a major pathogen in the respiratory tract infection, while retaining Gram-negative activity. Among them, 1-cyclopropyl-6-fluoro-1, 4-dihydro-5-methyl-7-(3-methyl-1-piperazinyl)-4-oxo-3-quinolinecarboxyli c acid hydrochloride (grepafloxacin) exhibited potent in vitro antibacterial activity against Gram-positive bacteria such as Streptococcus pneumoniae and high in vivo efficacy on the experimental systemic infections caused by the Gram-positive and -negative bacteria tested. It also showed a high distribution to the lung and bronchoalveolar lavage fluid in comparison to reference drugs and is now undergoing clinical evaluation.
authors.affiliation: Microbiological Research Institute, Otsuka Pharmaceutical Co., Ltd, Tokushima, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Miyamoto
authors.forename: H
authors.initials: H
authors.lastname: Yamashita
authors.forename: H
authors.initials: H
authors.lastname: Ueda
authors.forename: H
authors.initials: H
authors.lastname: Tamaoka
authors.forename: K
authors.initials: K
authors.lastname: Ohmori
authors.forename: K
authors.initials: K
authors.lastname: Nakagawa
mesh_terms: D042462:4-Quinolones; D000818:Animals; D000890:Anti-Infective Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D004352:Drug Resistance, Microbial; D004927:Escherichia coli Infections / Q000188:drug therapy; D006090:Gram-Negative Bacteria / Q000187:drug effects; D006094:Gram-Positive Bacteria / Q000187:drug effects; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D015394:Molecular Structure; D011008:Pneumococcal Infections / Q000188:drug therapy; D051381:Rats; D012141:Respiratory Tract Infections / Q000188:drug therapy; D013290:Streptococcal Infections / Q000188:drug therapy; D013296:Streptococcus pneumoniae / Q000187:drug effects; D013329:Structure-Activity Relationship; D014018:Tissue Distribution
chemical_list: D042462:4-Quinolones; D000890:Anti-Infective Agents