Synthesis and structure-activity relationship studies of highly potent novel oxazolidinone antibacterials.
Novel antibacterial biaryl oxazolidinones bearing an aza-, an oxa-, or a thiabicyclo[3.1.0]hex-6-yl ring system were synthesized, and their in vitro antibacterial activity and structure-activity relationships (SAR) were evaluated. Most of the synthesized biaryl bicyclo[3.1.0]hex-6-yl oxazolidinones showed good antibacterial activity against the Gram-positive and -negative bacteria tested. Regarding SAR trends among the C-ring subtypes, the pyridyl ring was preferable to the phenyl ring. The results showed that the structural variety of the C-ring has a greater impact on antibacterial activity than that of the B-ring. A cyano group at the D-ring C-6 position plays an important role in the highly potent antibacterial activity.
Komine
Takashi
T
Discovery Research Laboratories, Kyorin Pharmaceutical Co., Ltd., 2399-1, Nogi, Nogi-Machi, Shimotsuga-Gun, Tochigi, 329-0114, Japan.
Kojima
Akihiko
A
Asahina
Yoshikazu
Y
Saito
Tatsuhiro
T
Takano
Hisashi
H
Shibue
Taku
T
Fukuda
Yasumichi
Y
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D050296:Microbial Viability / Q000187:drug effects; D015394:Molecular Structure; D023303:Oxazolidinones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D000900:Anti-Bacterial Agents; D023303:Oxazolidinones