title: Studies on pyridonecarboxylic acids. 1. Synthesis and antibacterial evaluation of 7-substituted-6-halo-4-oxo-4H-[1,3]thiazeto[3,2-a]quinoline-3- carboxylic acids.
abstract: A series of [1,3]thiazeto[3,2-a]quinoline-3-carboxylic acids and their esters were prepared and evaluated for antibacterial activity. The derivatives with a hydrogen or methyl group at C-1, fluorine at C-6, and piperazinyl or 4-methyl-1-piperazinyl group at C-7 showed superior in vitro antibacterial activity, and the derivatives with 4-methyl-1-piperazinyl group at C-7 had potent in vivo activity. Compound 29a (NM394) showed excellent in vitro antibacterial activity and low toxicity but poor absorption from the gastrointestinal tract. Compound 29ee (NM441), an N-[(5-methyl-2-oxo-1,3-dioxol-4-yl)methyl] derivative of 29a, was found to possess a favorable pharmacokinetic profile and oral activity superior to that of ciprofloxacin in experimental animals.
authors.affiliation: Research Laboratories, Nippon Shinyaku Company, Ltd., Kyoto, Japan.
authors.forename: J
authors.initials: J
authors.lastname: Segawa
authors.forename: M
authors.initials: M
authors.lastname: Kitano
authors.forename: K
authors.initials: K
authors.lastname: Kazuno
authors.forename: M
authors.initials: M
authors.lastname: Matsuoka
authors.forename: I
authors.initials: I
authors.lastname: Shirahase
authors.forename: M
authors.initials: M
authors.lastname: Ozaki
authors.forename: M
authors.initials: M
authors.lastname: Matsuda
authors.forename: Y
authors.initials: Y
authors.lastname: Tomii
authors.forename: M
authors.initials: M
authors.lastname: Kise
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000890:Anti-Infective Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity; D002264:Carboxylic Acids / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity; D004927:Escherichia coli Infections / Q000188:drug therapy; D024841:Fluoroquinolones; D008297:Male; D051379:Mice; D008826:Microbial Sensitivity Tests; D011552:Pseudomonas Infections / Q000188:drug therapy; D015363:Quinolones / Q000138:chemical synthesis*; D013329:Structure-Activity Relationship
chemical_list: D000890:Anti-Infective Agents; D002264:Carboxylic Acids; D024841:Fluoroquinolones; D015363:Quinolones