title: Biological evaluation of isothiazoloquinolones containing aromatic heterocycles at the 7-position: In vitro activity of a series of potent antibacterial agents that are effective against methicillin-resistant Staphylococcus aureus.
abstract: We synthesized a diverse series of 9H-isothiazolo[5,4-b]quinoline-3,4-diones containing heteroaromatic groups at the 7-position via palladium-catalyzed cross-coupling. Many of these compounds demonstrated potent antistaphylococcal activity (MICs 2 microg/mL) against a multi-drug-resistant strain (ATCC 700699) and low cytotoxic activity (CC(50)>100 microM) against the human cell line Hep2 (laryngeal carcinoma).
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: Yongsheng
authors.initials: Y
authors.lastname: Song
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: 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; D045744:Cell Line, Tumor; D003500:Cyclization; D005461:Fluorine / Q000737:chemistry; D006801:Humans; D016106:Methicillin Resistance; D015394:Molecular Structure; D015363:Quinolones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000502:physiology; D013329:Structure-Activity Relationship; D013438:Sulfhydryl Compounds / Q000737:chemistry*
chemical_list: D000900:Anti-Bacterial Agents; D001391:Azo Compounds; D015363:Quinolones; D013438:Sulfhydryl Compounds; D005461:Fluorine