Synthesis of Dihydrofuroaporphine Derivatives: Identification of a Potent and Selective Serotonin 5-HT1A Receptor Agonist
文献类型：期刊论文
| 作者 | Liu, Zhili1; Zhang, Hai2; Ye, Na1; Zhang, Jing1; Wu, QianQian2; Sun, Peihua2; Li, Linyong2; Zhen, Xuechu2; Zhang, Ao1
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| 刊名 | JOURNAL OF MEDICINAL CHEMISTRY
 |
| 出版日期 | 2010-02-11 |
| 卷号 | 53期号:3页码:1319-1328 |
| ISSN号 | 0022-2623 |
| DOI | 10.1021/jm9015763 |
| 文献子类 | Article |
| 英文摘要 | A series of new aporphine analogues were synthesized and pharmacologically evaluated. 11-Allyloxy-(17), 11-propargyloxy-(20), and dihydrofuro-(19) aporphines displayed the highest affinity at the 5-HT1A receptor with K-i values of 12.0, 14.0, and 6.7 nM, respectively. The high binding potential of the diastereomeric mixture of aporphine 19 was found residing in the cis-diastereomer (cis-19). [S-35]GTP gamma S function assays on 5-HT1A receptor indicated that aporphines 17 and 20 were partial agonists, while trans-19 behaved as a high efficacy full antagonist and cis-19 was a full agonist. The agonistic property of cis-19 at the 5-HT1A receptor was further confirmed in vitro and in vivo. This compound may be useful as a potential treatment for anxiety. |
| WOS关键词 | VENTRAL TEGMENTAL AREA ; NIGRAL DOPAMINE NEURONS ; ELEVATED PLUS-MAZE ; (R)-APORPHINES SYNTHESIS ; PARKINSONS-DISEASE ; RAPHE NUCLEUS ; RAT ; PHARMACOLOGY ; ANXIETY ; COMPLICATIONS |
| 资助项目 | Chinese National Science Foundation[30772625] ; Chinese National Science Foundation[30672517] ; National Science Technology[2009ZX09103-062] ; National Science Technology[2009ZX09301-001] ; [2007AA022163] |
| WOS研究方向 | Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:000274270900036 |
| 出版者 | AMER CHEMICAL SOC |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/278972]  |
| 专题 | 药理学第二研究室 药物化学研究室 |
| 通讯作者 | Zhen, Xuechu |
| 作者单位 | 1.Chinese Acad Sci, SOMCL, Shanghai 201203, Peoples R China 2.Chinese Acad Sci, Shanghai Inst Mat Med, Neuropharmacol Lab, Shanghai 201203, Peoples R China; |
| 推荐引用方式 GB/T 7714 | Liu, Zhili,Zhang, Hai,Ye, Na,et al. Synthesis of Dihydrofuroaporphine Derivatives: Identification of a Potent and Selective Serotonin 5-HT1A Receptor Agonist[J]. JOURNAL OF MEDICINAL CHEMISTRY,2010,53(3):1319-1328. |
| APA | Liu, Zhili.,Zhang, Hai.,Ye, Na.,Zhang, Jing.,Wu, QianQian.,...&Zhang, Ao.(2010).Synthesis of Dihydrofuroaporphine Derivatives: Identification of a Potent and Selective Serotonin 5-HT1A Receptor Agonist.JOURNAL OF MEDICINAL CHEMISTRY,53(3),1319-1328. |
| MLA | Liu, Zhili,et al."Synthesis of Dihydrofuroaporphine Derivatives: Identification of a Potent and Selective Serotonin 5-HT1A Receptor Agonist".JOURNAL OF MEDICINAL CHEMISTRY 53.3(2010):1319-1328. |
入库方式： OAI收割
来源：上海药物研究所
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