title: Structure-activity relationship of quinolone antibacterial agents: the effects of C-2 substitution.
abstract: Very little is known about the structure-activity relationship of quinolone antibacterials at the 2-position. Because of the loss of biological activity with 2-methyl and 2-hydroxyl substitution, modifications at C-2 were generally considered to be unfavourable. Quinolone derivatives having a ring between positions 1 and 2 were recently shown to have biological activity. The sulfur-bridged analogs such as the benzothiazolo[3,2-a]quinolone, KB-5246 and NAD-394 have been reported to be highly active in vitro. The authors have synthesized 2-methylthiociprofloxacin, 2-methylofloxacin, the 5-oxopyrrolo[1,2-a]quinoline and isothiazolonaphthyridine to assess the importance of the sulfur atom on biological activity as well as the effect of C-2 substituent on the spatial arrangements of N-1 or the 3-carboxylic group. It was found that the planarity between the 4-keto and 3-carboxylic acid groups of quinoline molecules is the most important criterion for biological activity. The syntheses of the above four compounds are also described.
authors.affiliation: Anti-infective Research Division, Abbott Laboratories, Abbott Park, IL 60064-3500.
authors.forename: D T
authors.initials: DT
authors.lastname: Chu
authors.forename: I M
authors.initials: IM
authors.lastname: Lico
authors.forename: A K
authors.initials: AK
authors.lastname: Claiborne
authors.forename: J J
authors.initials: JJ
authors.lastname: Plattner
authors.forename: A G
authors.initials: AG
authors.lastname: Pernet
mesh_terms: D000890:Anti-Infective Agents / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D015363:Quinolones / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D059005:Topoisomerase II Inhibitors
chemical_list: D000890:Anti-Infective Agents; D015363:Quinolones; D059005:Topoisomerase II Inhibitors