Design, Synthesis, and Structure-Activity Relationship Studies of Highly Potent Novel Benzoxazinyl-Oxazolidinone Antibacterial Agents
文献类型：期刊论文
| 作者 | Xin, Qisheng1; Fan, Houxing1; Guo, Bin1 ; He, Huili1; Gao, Suo1; Wang, Hui2; Huang, Yanqin3; Yang, Yushe1
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| 刊名 | JOURNAL OF MEDICINAL CHEMISTRY
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| 出版日期 | 2011-11-10 |
| 卷号 | 54期号:21页码:7493-7502 |
| ISSN号 | 0022-2623 |
| DOI | 10.1021/jm200614t |
| 文献子类 | Article |
| 英文摘要 | A series of novel benzoxazinyl-oxazolidinones bearing nonaromatic heterocycle or aryl groups were designed and synthesized. Their in vitro and in vivo antibacterial activities were investigated. Most of the (3S, 3aS) biaryl benzoxazinyl-oxazolidinones exhibited potent activity against Gram-positive pathogens. SAR trends were observed; a pyridyl C ring was preferable to other 5- or 6-member aryl C rings, while fluorine substitution on the B ring generated derivatives with reduced activity. Various substituent group positions on the pyridyl ring were also evaluated. The resulting compounds displayed excellent activity against linezolid-resistant strains. Compound 45 exhibited excellent in vitro activity, with a MIC value of 0.25-0.5 mu g/mL against MASA and an activity against linezolid-resistant strains of 8-16-fold higher potency than linezolid. In a MRSA systemic infection model, compound 45 displayed an ED50 < 5.0 mg/kg, a potency that is nearly 3-fold better than that of linezolid. This compound also showed excellent pharmacokinetic profiles, with a half-life of more than 5 h as well as an oral bioavailability of 81% in rats. |
| WOS关键词 | TRICYCLIC FUSED OXAZOLIDINONE ; STAPHYLOCOCCUS-AUREUS ; RESISTANCE ; RING |
| 资助项目 | National Natural Science Foundation of China[20672125] ; National Science and Technology Major Project of China[2009ZX09301-001] |
| WOS研究方向 | Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:000296408100007 |
| 出版者 | AMER CHEMICAL SOC |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/278336]  |
| 专题 | 药物化学研究室 中科院受体结构与功能重点实验室 新药研究国家重点实验室 |
| 通讯作者 | Yang, Yushe |
| 作者单位 | 1.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai Inst Biol Sci, State Key Lab Drug Res, Shanghai 201203, Peoples R China; 2.China Pharmaceut Univ, Dept Microbiol, Nanjing 210009, Jiangsu Provinc, Peoples R China; 3.MicuRx Pharmaceut Inc, Shanghai 201203, Peoples R China |
| 推荐引用方式 GB/T 7714 | Xin, Qisheng,Fan, Houxing,Guo, Bin,et al. Design, Synthesis, and Structure-Activity Relationship Studies of Highly Potent Novel Benzoxazinyl-Oxazolidinone Antibacterial Agents[J]. JOURNAL OF MEDICINAL CHEMISTRY,2011,54(21):7493-7502. |
| APA | Xin, Qisheng.,Fan, Houxing.,Guo, Bin.,He, Huili.,Gao, Suo.,...&Yang, Yushe.(2011).Design, Synthesis, and Structure-Activity Relationship Studies of Highly Potent Novel Benzoxazinyl-Oxazolidinone Antibacterial Agents.JOURNAL OF MEDICINAL CHEMISTRY,54(21),7493-7502. |
| MLA | Xin, Qisheng,et al."Design, Synthesis, and Structure-Activity Relationship Studies of Highly Potent Novel Benzoxazinyl-Oxazolidinone Antibacterial Agents".JOURNAL OF MEDICINAL CHEMISTRY 54.21(2011):7493-7502. |
入库方式： OAI收割
来源：上海药物研究所
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