Design, Synthesis, and Structure-Activity Relationship Studies of Novel Thioether Pleuromutilin Derivatives as Potent Antibacterial Agents
文献类型：期刊论文
| 作者 | Ling, Chenyu1; Fu, Liqiang1; Gao, Suo1; Chu, Wenjing1; Wang, Hui2; Huang, Yanqin3; Chen, Xiaoyan1 ; Yang, Yushe1
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| 刊名 | JOURNAL OF MEDICINAL CHEMISTRY
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| 出版日期 | 2014-06-12 |
| 卷号 | 57期号:11页码:4772-4795 |
| ISSN号 | 0022-2623 |
| DOI | 10.1021/jm500312x |
| 文献子类 | Article |
| 英文摘要 | A series of novel thioether pleuromutilin derivatives incorporating various heteroaromatic substituents into the C14 side chain have been reported. Structure-activity relationship (SAR) studies resulted in compounds 52 and 55 with the most potent in vitro antibacterial activity among the series (MIC = 0.031-0.063 mu g/mL). Further optimization to overcome the poor water solubility of compound 55 resulted in compounds 87, 91, 109, and 110 possessing good in vitro antibacterial activity with increased hydrophilicity. Compound 114, the water-soluble phosphate prodrug of compound 52, was also prepared and evaluated. Among the derivatives, compound 110 showed moderate pharmacokinetic profiles and good in vivo efficacy in both MSSA and MRSA systemic infection models. Compound 110 was further evaluated in CYP450 inhibition assay and displayed intermediate in vitro inhibition of CYP3A4. |
| WOS关键词 | ENHANCED ANTIMICROBIAL ACTIVITY ; INFECTIOUS-DISEASES SOCIETY ; GRAM-POSITIVE PATHOGENS ; IN-VITRO ; ARYL HALIDES ; 81.723 HFU ; ANTIBIOTICS ; RETAPAMULIN ; RESISTANT ; TIAMULIN |
| WOS研究方向 | Pharmacology & Pharmacy |
| 语种 | 英语 |
| 出版者 | AMER CHEMICAL SOC |
| WOS记录号 | WOS:000337336600026 |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/277025]  |
| 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.China Pharmaceut Univ, Dept Microbiol, Nanjing 210009, Jiangsu, Peoples R China; 3.MicuRx Pharmaceut Inc, Shanghai 201203, Peoples R China |
| 推荐引用方式 GB/T 7714 | Ling, Chenyu,Fu, Liqiang,Gao, Suo,et al. Design, Synthesis, and Structure-Activity Relationship Studies of Novel Thioether Pleuromutilin Derivatives as Potent Antibacterial Agents[J]. JOURNAL OF MEDICINAL CHEMISTRY,2014,57(11):4772-4795. |
| APA | Ling, Chenyu.,Fu, Liqiang.,Gao, Suo.,Chu, Wenjing.,Wang, Hui.,...&Yang, Yushe.(2014).Design, Synthesis, and Structure-Activity Relationship Studies of Novel Thioether Pleuromutilin Derivatives as Potent Antibacterial Agents.JOURNAL OF MEDICINAL CHEMISTRY,57(11),4772-4795. |
| MLA | Ling, Chenyu,et al."Design, Synthesis, and Structure-Activity Relationship Studies of Novel Thioether Pleuromutilin Derivatives as Potent Antibacterial Agents".JOURNAL OF MEDICINAL CHEMISTRY 57.11(2014):4772-4795. |
入库方式： OAI收割
来源：上海药物研究所
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