Solubility-Driven Optimization of (Pyridin-3-yl) Benzoxazinyl-oxazolidinones Leading to a Promising Antibacterial Agent
文献类型：期刊论文
| 作者 | Guo, Bin1 ; Fan, Houxing1; Xin, Qisheng1; Chu, Wenjing1; Wang, Hui3; Huang, Yanqin2; Chen, Xiaoyan1; Yang, Yushe1
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| 刊名 | JOURNAL OF MEDICINAL CHEMISTRY
 |
| 出版日期 | 2013-03-28 |
| 卷号 | 56期号:6页码:2642-2650 |
| ISSN号 | 0022-2623 |
| DOI | 10.1021/jm4000598 |
| 文献子类 | Article |
| 英文摘要 | The solubility-driven structural modification of (pyridin-3-yl) benzoxazinyl-oxazolidinones is described, which resulted in the development of a new series of benzoxazinyl-oxazolidinone analogues with high antibacterial activity against Gram-positive pathogens, including that against linezolid-resistant strains and low hERG inhibition. With regard to structure-activity relationship (SAR) trends among the various substituents on the pyridyl ring, relatively small and nonbasic substituents were preferable to sterically demanding or basic substituents. Oxazolidinone ring substitution on the pyridyl ring generated analogues with antibacterial activity superior to imidazolidinone ring. Solubility was enhanced by the incorporation of polar groups, especially when compounds were converted to their prodrugs. Among the prodrugs, compound 85 exhibited excellent solubility and a good pharmacokinetic profile. In a MRSA systemic infection model, compound 85 displayed an ED50 = 5.00 mg/kg, a potency that is 2-fold better than that of linezolid. |
| WOS关键词 | INFECTIOUS-DISEASES SOCIETY ; STAPHYLOCOCCUS-AUREUS ; RESISTANCE ; AMERICA |
| 资助项目 | National Natural Science Foundation of China[81172922] |
| WOS研究方向 | Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:000317032200038 |
| 出版者 | AMER CHEMICAL SOC |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/277687]  |
| 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, State Key Lab Drug Res, Shanghai 201203, Peoples R China; 2.MicuRx Pharmaceut Inc, Shanghai 201203, Peoples R China 3.China Pharmaceut Univ, Dept Microbiol, Nanjing 210009, Jiangsu, Peoples R China; |
| 推荐引用方式 GB/T 7714 | Guo, Bin,Fan, Houxing,Xin, Qisheng,et al. Solubility-Driven Optimization of (Pyridin-3-yl) Benzoxazinyl-oxazolidinones Leading to a Promising Antibacterial Agent[J]. JOURNAL OF MEDICINAL CHEMISTRY,2013,56(6):2642-2650. |
| APA | Guo, Bin.,Fan, Houxing.,Xin, Qisheng.,Chu, Wenjing.,Wang, Hui.,...&Yang, Yushe.(2013).Solubility-Driven Optimization of (Pyridin-3-yl) Benzoxazinyl-oxazolidinones Leading to a Promising Antibacterial Agent.JOURNAL OF MEDICINAL CHEMISTRY,56(6),2642-2650. |
| MLA | Guo, Bin,et al."Solubility-Driven Optimization of (Pyridin-3-yl) Benzoxazinyl-oxazolidinones Leading to a Promising Antibacterial Agent".JOURNAL OF MEDICINAL CHEMISTRY 56.6(2013):2642-2650. |
入库方式： OAI收割
来源：上海药物研究所
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