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.
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).
Wiles
Jason A
JA
Achillion Pharmaceuticals, Inc., 300 George Street, New Haven, CT 06511-6653, USA. jwiles@achillion.com
Song
Yongsheng
Y
Wang
Qiuping
Q
Lucien
Edlaine
E
Hashimoto
Akihiro
A
Cheng
Jijun
J
Marlor
Christopher W
CW
Ou
Yangsi
Y
Podos
Steven D
SD
Thanassi
Jane A
JA
Thoma
Christy L
CL
Deshpande
Milind
M
Pucci
Michael J
MJ
Bradbury
Barton J
BJ
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*
D000900:Anti-Bacterial Agents; D001391:Azo Compounds; D015363:Quinolones; D013438:Sulfhydryl Compounds; D005461:Fluorine