title: Isothiazoloquinolones containing functionalized aromatic hydrocarbons at the 7-position: synthesis and in vitro activity of a series of potent antibacterial agents with diminished cytotoxicity in human cells.
abstract: This report describes 9H-isothiazolo[5,4-b]quinoline-3,4-diones (ITQs) containing aromatic groups at the 7-position that were prepared using palladium-catalyzed cross-coupling and tested against a panel of susceptible and resistant bacteria. In general, these compounds were more effective against Gram-positive than Gram-negative organisms. Many of the ITQs were more potent than contemporary quinolones and displayed a particularly strong antistaphylococcal activity against a clinically important, multi-drug-resistant strain. In contrast with ITQs reported previously, several of the analogues described in this Letter demonstrated low cytotoxic activity against a human cell line.
authors.affiliation: Achillion Pharmaceuticals, Inc., 300 George Street, New Haven, CT 06511-6653, USA. jwiles@achillion.com
authors.forename: Jason A
authors.initials: JA
authors.lastname: Wiles
authors.forename: Qiuping
authors.initials: Q
authors.lastname: Wang
authors.forename: Edlaine
authors.initials: E
authors.lastname: Lucien
authors.forename: Akihiro
authors.initials: A
authors.lastname: Hashimoto
authors.forename: Yongsheng
authors.initials: Y
authors.lastname: Song
authors.forename: Jijun
authors.initials: J
authors.lastname: Cheng
authors.forename: Christopher W
authors.initials: CW
authors.lastname: Marlor
authors.forename: Yangsi
authors.initials: Y
authors.lastname: Ou
authors.forename: Steven D
authors.initials: SD
authors.lastname: Podos
authors.forename: Jane A
authors.initials: JA
authors.lastname: Thanassi
authors.forename: Christy L
authors.initials: CL
authors.lastname: Thoma
authors.forename: Milind
authors.initials: M
authors.lastname: Deshpande
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Pucci
authors.forename: Barton J
authors.initials: BJ
authors.lastname: Bradbury
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D001391:Azo Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology / Q000633:toxicity*; D002460:Cell Line; D004926:Escherichia coli / Q000187:drug effects / Q000201:enzymology; D006801:Humans; D006841:Hydrocarbons, Aromatic / Q000737:chemistry*; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D011804:Quinolines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology* / Q000633:toxicity; D013211:Staphylococcus aureus / Q000187:drug effects / Q000201:enzymology; D013438:Sulfhydryl Compounds / Q000737:chemistry*
chemical_list: D000900:Anti-Bacterial Agents; D001391:Azo Compounds; D006841:Hydrocarbons, Aromatic; D011804:Quinolines; D013438:Sulfhydryl Compounds