Synthesis and in聽vitro/in聽vivo antibacterial activity of oxazolidinones having thiocarbamate at C-5 on the A-ring and an amide- or urea-substituted [1,2,5]triazepane or [1,2,5]oxadiazepane as the C-ring

详细信息    查看全文

• 作者：Hideyuki Suzuki ; Iwao Utsunomiya ; Koichi Shudo ; Norio Fukuhara ; Tsutomu Iwaki ; Tatsuro Yasukata
• 关键词：Antibacterial ; Oxazolidinone ; Methicillin-resistant Staphylococcus aureus ; [1 ; 2 ; 5]Triazepane ; [1 ; 2 ; 5]Oxadiazepane
• 刊名：European Journal of Medicinal Chemistry
• 出版年：November, 2013
• 年：2013
• 卷：69
• 期：Complete
• 页码：262-277
• 全文大小：526 K

文摘

Oxazolidinones bearing a seven-membered [1,2,5]triazepane or [1,2,5]oxadiazepane heterocycle substituted with an amide or urea functionality as the C-ring and having a [1,2,3]triazole, a thiocarbamate, an isoxazole-3-ylamino, or a thioacetamide C-5 side chain unit on the A-ring instead of the typical acetamide were synthesized and their in聽vitro antibacterial activities towards various pathogens were evaluated. Several derivatives exhibited potent in聽vitro antibacterial activity toward not only Gram-positive, but also Gram-negative and linezolid-resistant pathogens. The in聽vivo therapeutic effects of amide 11a and ureas 16e, 17a were 2- to 3-fold greater than that of linezolid in a systemic mouse infection model treated by intravenous administration. Furthermore, compounds 11a and 17a showed lower monoamine oxidase (MAO)-inhibitory activity than our previously reported potent oxazolidinone antibacterials 3a and 3b.