Synthesis and SAR Study of Opioid Receptor Ligands: Mono- and Bis-Indolomorphinans
文献类型：期刊论文
| 作者 | Li, Fuying2; Yin, Chenlei1; Chen, Jie3; Liu, Jinggen3 ; Xie, Xin1; Zhang, Ao2
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| 刊名 | CHEMICAL BIOLOGY & DRUG DESIGN
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| 出版日期 | 2009-10 |
| 卷号 | 74期号:4页码:335-342 |
| 关键词 | indole morphinans scaffold opioid receptor structure-activity relationships |
| ISSN号 | 1747-0277 |
| DOI | 10.1111/j.1747-0285.2009.00849.x |
| 文献子类 | Article; Proceedings Paper |
| 英文摘要 | Mono- and bis-indolomorphinans were synthesized through a multi-step synthetic approach from the alkaloid, thebaine, to further explore the C-ring SAR (structure-activity relationship) of morphinan scaffold. Both mono-indoles displayed good binding affinity and selectivity for the delta receptor, with compound 6b possessed the highest K-i value of 1.45 nm at this receptor. Bisindolomorphinans 7a,b did not have appreciable affinity for both delta and kappa receptors, but moderate binding at the mu receptor was observed. Functional assays indicated that the newly synthesized mono-indole 6b was delta-agonist, opposite to the delta-antagonist profile of naltrindole. Bisindoles 7a,b were mu-agonists. This work further confirms that the phenol component in opioids is essential for higher binding to the opioid receptors. The different binding ability, receptor selectivity, and the functional activity profiles of naltrindole 2, monoindole 6b, and bisindole 7b clearly indicated that they interact with the opioid receptors in different modes. |
| WOS关键词 | MU-AGONIST/DELTA ANTAGONIST ; 4-HYDROXYL GROUP ; BIOLOGICAL-ACTIVITY ; BIRCH REDUCTION ; MORPHINE ; ELIMINATION ; NALTRINDOLE ; DERIVATIVES ; OXYMORPHONE ; SELECTIVITY |
| WOS研究方向 | Biochemistry & Molecular Biology ; Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:000269703900002 |
| 出版者 | WILEY |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/279109]  |
| 专题 | 药物化学研究室 |
| 通讯作者 | Zhang, Ao |
| 作者单位 | 1.Chinese Acad Sci, Shanghai Inst Mat Med, Natl Ctr Drug Screening, Shanghai 201203, Peoples R China; 2.Chinese Acad Sci, Shanghai Inst Mat Med, SOMCL, Shanghai 201203, Peoples R China; 3.Chinese Acad Sci, Shanghai Inst Mat Med, Neuropharmacol Lab, Shanghai 201203, Peoples R China |
| 推荐引用方式 GB/T 7714 | Li, Fuying,Yin, Chenlei,Chen, Jie,et al. Synthesis and SAR Study of Opioid Receptor Ligands: Mono- and Bis-Indolomorphinans[J]. CHEMICAL BIOLOGY & DRUG DESIGN,2009,74(4):335-342. |
| APA | Li, Fuying,Yin, Chenlei,Chen, Jie,Liu, Jinggen,Xie, Xin,&Zhang, Ao.(2009).Synthesis and SAR Study of Opioid Receptor Ligands: Mono- and Bis-Indolomorphinans.CHEMICAL BIOLOGY & DRUG DESIGN,74(4),335-342. |
| MLA | Li, Fuying,et al."Synthesis and SAR Study of Opioid Receptor Ligands: Mono- and Bis-Indolomorphinans".CHEMICAL BIOLOGY & DRUG DESIGN 74.4(2009):335-342. |
入库方式： OAI收割
来源：上海药物研究所
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